Zvyšují střevní propustnost - vyloučit
Acer nikoense
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Acer nikoense
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Acetaldehyde
- A biological metabolite of ethanol [9]
Acetaldehyde
- A biological metabolite of ethanol [9]
Aditiva v potravinách
- Nanoemulsion
- Surfactants
- Salt nanowires
- Nanostructured lipid carriers
- Nanotechnology using organic solvents
- sugars
- Bacterial enzymes
- L-alanine
- tryptophan
- Polysaccharide chitosan [12]
Aditiva v potravinách
- Nanoemulsion
- Surfactants
- Salt nanowires
- Nanostructured lipid carriers
- Nanotechnology using organic solvents
- sugars
- Bacterial enzymes
- L-alanine
- tryptophan
- Polysaccharide chitosan [12]
AGEs
- Final product of a chain of reactions
- Reducing sugars spontaneously react with
- Aminopeptides
- lipids
- Nucleic acids [10]
- Browning products (glycotoxins) [10]
- Due to the Maillard reaction [10]
- Amadori products are formed later in the reaction [10]
- Best-known AGEs
- Carboxymethyllysine (CML)
- Pentosidine
- Several measurement techniques
- Fluorescent nature [10]
- AGEs induce inflammation
- Which may further exacerbate IP [10]
- Formation of AGE/ALE is strongly accelerated by cooking [10]
- Simple diffusion ze střeva [10]
- Largely eliminated by hepatic sinusoidal Kupffer and endothelial cells [10]
- Urinary excretion of AGEs [10]
- Pyrroline and pentosidine
- Well absorbed
- Peptide-bound Amadori products
- Not well absorbed [10]
- Permanent recombination among AGEs [10]
- Strongly roasting
- Typically increases allergenicity of peanuts [10]
- Carboxymethyllysine
- Significantly higher in infant formulas than in breast milk [10]
- High-fat meals have the highest AGE content
- More than meat and carbohydrate-rich meals [10]
- Broiling and frying generates more glycated compounds than roasting [10]
- Least amount of glycated compounds is generated by boiling [10]
- Safest cooking method
- Appears to be slow boiling at reasonable temperatures [10]
- Alpha-dicarbonyls
- Most prone to form glycation
- Found naturally in green coffee
- Increase if beans are subjected to light or medium roasting
- Dark roasted coffee contains fewer of these compounds [10]
- Very high temperatures during food processing
- Denaturate proteins that have lower glycation capacity [10]
- Recognition of epitopes by IgE is diminished [10]
- protein digestibility is lower if the diet is rich in browning products [10]
- Glycation of food allergens increases T-cell immunogenicity of food allergens [10]
- Postprandial leptin concentrations
- Are lower in diabetics
- Improve if meals are heated with low temperatures [10]
- Methylglyoxal
- A strong glycating agent
- Also present in many beverages
- Tea, coffee, diet coke and soy sauce
- Have a high AGE content [10]
- If kidney function is compromised in patients
- Suggests that dietary AGEs add to those synthesized endogenously by the high glucose levels [10]
- Methylglyoxal or glyoxal
- Potent glycating metabolites
- Exposure of intestinal CaCO2 cells in vitro is followed by
- Increased IL-6 and IL-8
- Amplify the effects of TNF-? and IL-1ß [10]
- AGEs may cause intestinal inflammation on their own [10]
- AGEs from casein form a complex with serum albumin
- Receptor for AGE (RAGE) is stimulated
- Induces inflammation
- RAGE is expressed in the intestinal epithelium
- Increases when interferon ? or TNF-? are high, such as in IBD [10]
- NF-B is activated [10]
- IgE antibodies were elevated 4x více against processed food antigens in 30% of humans --When compared with raw food antigens [10]
- Allergenicity of peanuts
- Relates to their curing temperature (77 °C) and roasting
- Similar findings have been reported for soybean-based products [10]
- AGEs can also modify the gut microbiota [10]
- Fructose
- Relatively strong glycating sugar
- Widely used in sweetened beverages and corn syrup [10]
- Fructose is more reactive than glucose in AGE formation [10]
- Rats are fed a high-fructose diet
- AGE pentosidine accumulates in the aorta and skin [10]
- Glycation and oxidative stress occurred preferentially in fructose-fed animals [10]
- Diabetogenic effect of fructose occurs via increases in uric acid [10]
- Chronic diet including 1% methylglyoxal
- Induces insulin resistance
- Induces salt-sensitivity in Sprague-Dawley rats [10]
- High AGE levels
- Leads to adipocyte dysfunction
- Reduced leptin and adiponectin production
- Increased oxidative stress [10]
- Diabetic db/db mice
- Restricted intake of oral AGEs improved insulin sensitivity [10]
- AGEs lead to insulin resistance via the AGE receptor [10]
- Direct structural modifications of insulin itself
- By methylglyoxal have also been shown [10]
- Harmful association between nutrition, hyperglycemia and impaired renal function may relate to AGE intake in humans [10]
- A high-fat diet increases visceral AGEs
- Promotes DNA fragmentation and apoptosis in the liver [10]
AGEs
- Final product of a chain of reactions
- Reducing sugars spontaneously react with
- Aminopeptides
- lipids
- Nucleic acids [10]
- Browning products (glycotoxins) [10]
- Due to the Maillard reaction [10]
- Amadori products are formed later in the reaction [10]
- Best-known AGEs
- Carboxymethyllysine (CML)
- Pentosidine
- Several measurement techniques
- Fluorescent nature [10]
- AGEs induce inflammation
- Which may further exacerbate IP [10]
- Formation of AGE/ALE is strongly accelerated by cooking [10]
- Simple diffusion ze střeva [10]
- Largely eliminated by hepatic sinusoidal Kupffer and endothelial cells [10]
- Urinary excretion of AGEs [10]
- Pyrroline and pentosidine
- Well absorbed
- Peptide-bound Amadori products
- Not well absorbed [10]
- Permanent recombination among AGEs [10]
- Strongly roasting
- Typically increases allergenicity of peanuts [10]
- Carboxymethyllysine
- Significantly higher in infant formulas than in breast milk [10]
- High-fat meals have the highest AGE content
- More than meat and carbohydrate-rich meals [10]
- Broiling and frying generates more glycated compounds than roasting [10]
- Least amount of glycated compounds is generated by boiling [10]
- Safest cooking method
- Appears to be slow boiling at reasonable temperatures [10]
- Alpha-dicarbonyls
- Most prone to form glycation
- Found naturally in green coffee
- Increase if beans are subjected to light or medium roasting
- Dark roasted coffee contains fewer of these compounds [10]
- Very high temperatures during food processing
- Denaturate proteins that have lower glycation capacity [10]
- Recognition of epitopes by IgE is diminished [10]
- protein digestibility is lower if the diet is rich in browning products [10]
- Glycation of food allergens increases T-cell immunogenicity of food allergens [10]
- Postprandial leptin concentrations
- Are lower in diabetics
- Improve if meals are heated with low temperatures [10]
- Methylglyoxal
- A strong glycating agent
- Also present in many beverages
- Tea, coffee, diet coke and soy sauce
- Have a high AGE content [10]
- If kidney function is compromised in patients
- Suggests that dietary AGEs add to those synthesized endogenously by the high glucose levels [10]
- Methylglyoxal or glyoxal
- Potent glycating metabolites
- Exposure of intestinal CaCO2 cells in vitro is followed by
- Increased IL-6 and IL-8
- Amplify the effects of TNF-? and IL-1ß [10]
- AGEs may cause intestinal inflammation on their own [10]
- AGEs from casein form a complex with serum albumin
- Receptor for AGE (RAGE) is stimulated
- Induces inflammation
- RAGE is expressed in the intestinal epithelium
- Increases when interferon ? or TNF-? are high, such as in IBD [10]
- NF-B is activated [10]
- IgE antibodies were elevated 4x více against processed food antigens in 30% of humans --When compared with raw food antigens [10]
- Allergenicity of peanuts
- Relates to their curing temperature (77 °C) and roasting
- Similar findings have been reported for soybean-based products [10]
- AGEs can also modify the gut microbiota [10]
- Fructose
- Relatively strong glycating sugar
- Widely used in sweetened beverages and corn syrup [10]
- Fructose is more reactive than glucose in AGE formation [10]
- Rats are fed a high-fructose diet
- AGE pentosidine accumulates in the aorta and skin [10]
- Glycation and oxidative stress occurred preferentially in fructose-fed animals [10]
- Diabetogenic effect of fructose occurs via increases in uric acid [10]
- Chronic diet including 1% methylglyoxal
- Induces insulin resistance
- Induces salt-sensitivity in Sprague-Dawley rats [10]
- High AGE levels
- Leads to adipocyte dysfunction
- Reduced leptin and adiponectin production
- Increased oxidative stress [10]
- Diabetic db/db mice
- Restricted intake of oral AGEs improved insulin sensitivity [10]
- AGEs lead to insulin resistance via the AGE receptor [10]
- Direct structural modifications of insulin itself
- By methylglyoxal have also been shown [10]
- Harmful association between nutrition, hyperglycemia and impaired renal function may relate to AGE intake in humans [10]
- A high-fat diet increases visceral AGEs
- Promotes DNA fragmentation and apoptosis in the liver [10]
AIDS
- Přechod do AIDS - zvýšení SP [7]
- Vznik průjmů
- Nad 20% pac. s AIDS
- glutamin 4d/d či 8g/d po 28 dní
- úprava SP (ne však signifikantní) [7]
- Doporučeno je: 20g/d a delší doba podání [7]
- SP roste s progresí HIV [7]
- V.s. vlivem přerůstání bakterií [7]
AIDS
- Přechod do AIDS - zvýšení SP [7]
- Vznik průjmů
- Nad 20% pac. s AIDS
- glutamin 4d/d či 8g/d po 28 dní
- úprava SP (ne však signifikantní) [7]
- Doporučeno je: 20g/d a delší doba podání [7]
- SP roste s progresí HIV [7]
- V.s. vlivem přerůstání bakterií [7]
Alcohol and its metabolites
- Impair the TJ barriers
- A jiná organická rozpouštědla !!! [12]
- Hexane k extrakci olejů ap. [12]
- Velká část sojových olejů [12]
- Increases paracellular permeability
- Induces alterations in TJ proteins
- Ethanol enhanced the transport of electrolytes and organic substances
Acetaldehyde
- Dissociates the PTP1B-E-cadherin-beta-catenin complex in Caco-2 cell monolayers
- Increased permeability
- Fermented food and many alcoholic beverages
- Can also contain significant amounts of acetaldehyde
- Cumulative carcinogen in the upper digestive tract of humans
Alcohol and its metabolites
- Impair the TJ barriers
- A jiná organická rozpouštědla !!! [12]
- Hexane k extrakci olejů ap. [12]
- Velká část sojových olejů [12]
- Increases paracellular permeability
- Induces alterations in TJ proteins
- Ethanol enhanced the transport of electrolytes and organic substances
Acetaldehyde
- Dissociates the PTP1B-E-cadherin-beta-catenin complex in Caco-2 cell monolayers
- Increased permeability
- Fermented food and many alcoholic beverages
- Can also contain significant amounts of acetaldehyde
- Cumulative carcinogen in the upper digestive tract of humans
Antibiotika
- Některá
- A strong correlation
- Level of caecal succinate
- Relative abundance of Clostridiaceae 1 family in the caecum [25]
- Level of acute phase protein haptoglobin in blood plasma [25]
Antibiotika
- Některá
- A strong correlation
- Level of caecal succinate
- Relative abundance of Clostridiaceae 1 family in the caecum [25]
- Level of acute phase protein haptoglobin in blood plasma [25]
Atopic dermatitis
- Involve dietary antigens
- Patients describe a dietary association to disease flares
- Many studies that have examined relatively small numbers of patients found no evidence of altered permeability
- Several studies found abnormalities in a subgroup of patients
- Some of these patients relief of symptoms has accompanied probiotic treatment
- Probiotics
- Reduced the skin disease
- Decreased elevated small intestinal permeability [4]
Atopic dermatitis
- Involve dietary antigens
- Patients describe a dietary association to disease flares
- Many studies that have examined relatively small numbers of patients found no evidence of altered permeability
- Several studies found abnormalities in a subgroup of patients
- Some of these patients relief of symptoms has accompanied probiotic treatment
- Probiotics
- Reduced the skin disease
- Decreased elevated small intestinal permeability [4]
Bacterial pathogens - tight junction structure and function
- Cholera
- Select enteric viruses
- Parasites
- May contribute to the development of chronic intestinal disorders
- Stress and infections cause perturbations in intestinal permeability [1]
Bacterial pathogens - tight junction structure and function
- Cholera
- Select enteric viruses
- Parasites
- May contribute to the development of chronic intestinal disorders
- Stress and infections cause perturbations in intestinal permeability [1]
Benzalkonium chloride
- At nontoxic levels
- Paracellular flux increases [12]
Benzalkonium chloride
- At nontoxic levels
- Paracellular flux increases [12]
CA-MLCK - constitutively active
- Myosin light chain kinase (CA-MLCK) within the epithelium
- Induces intestinal epithelial tight junction barrier loss
- Without associated epithelial damage
- Increased intestinal permeability
- To a degree similar to that seen in healthy first-degree relatives of CD patients
- CA-MLCK transgenic mice failed to develop spontaneous disease
- Did display subclinical immune activation
- Developed a more severe colitis with reduced survival in colitis model
- Onset of disease was markedly accelerated in CA-MLCK transgenic mice
- Intestinal epithelial tight junction barrier loss
- Can trigger mucosal immune activation, without causing disease
- Can also enhance the rate of disease progression in a susceptible individual [15]
CA-MLCK - constitutively active
- Myosin light chain kinase (CA-MLCK) within the epithelium
- Induces intestinal epithelial tight junction barrier loss
- Without associated epithelial damage
- Increased intestinal permeability
- To a degree similar to that seen in healthy first-degree relatives of CD patients
- CA-MLCK transgenic mice failed to develop spontaneous disease
- Did display subclinical immune activation
- Developed a more severe colitis with reduced survival in colitis model
- Onset of disease was markedly accelerated in CA-MLCK transgenic mice
- Intestinal epithelial tight junction barrier loss
- Can trigger mucosal immune activation, without causing disease
- Can also enhance the rate of disease progression in a susceptible individual [15]
Cadmium
- Damages the intestinal tract
- Usually the first internal organ to be exposed [27]
- Induces inflammation, increases intestinal permeability
- Disrupts "tight junctions [27]
- Mice - probiotic L. plantarum drinking water laced with cadmium, for eight weeks
- Quantity of cadmium excreted in the feces rose steadily during the study period
- As the bacteria became established in increasing numbers in the mice' intestines
- Mice that excreted greater cadmium in the feces had less cadmium in their tissues [27]
- Probiotics reduced the inflammation, reversed the disruption of tight junctions, and reduced intestinal permeability in the mice [27]
- Certain regions of Jiangxi Province in China
- Cadmium content of rice was way above the standard
- Probiotics might benefit people exposed to heavy metal pollution such as cadmium and lead [27]
- Industrial slag polluted the Jinzu river basin of Japan
- 1910s to the 1960s
- Contaminating local rice
- Itai-itai disease ("it hurts it hurts")
- Most severe manifestation of cadmium poisoning [27]
- Despite soil replacement in 1,500 hectares of paddy fields from 1980-2011
- Small number of cases of cadmium poisoning occurred during the '00s. [27]
- Toxic effects to liver, kidneys, bones, and reproductive system, are well documented
- Oxidative stress is an important mechanism of the toxicity [27]
Cadmium
- Damages the intestinal tract
- Usually the first internal organ to be exposed [27]
- Induces inflammation, increases intestinal permeability
- Disrupts "tight junctions [27]
- Mice - probiotic L. plantarum drinking water laced with cadmium, for eight weeks
- Quantity of cadmium excreted in the feces rose steadily during the study period
- As the bacteria became established in increasing numbers in the mice' intestines
- Mice that excreted greater cadmium in the feces had less cadmium in their tissues [27]
- Probiotics reduced the inflammation, reversed the disruption of tight junctions, and reduced intestinal permeability in the mice [27]
- Certain regions of Jiangxi Province in China
- Cadmium content of rice was way above the standard
- Probiotics might benefit people exposed to heavy metal pollution such as cadmium and lead [27]
- Industrial slag polluted the Jinzu river basin of Japan
- 1910s to the 1960s
- Contaminating local rice
- Itai-itai disease ("it hurts it hurts")
- Most severe manifestation of cadmium poisoning [27]
- Despite soil replacement in 1,500 hectares of paddy fields from 1980-2011
- Small number of cases of cadmium poisoning occurred during the '00s. [27]
- Toxic effects to liver, kidneys, bones, and reproductive system, are well documented
- Oxidative stress is an important mechanism of the toxicity [27]
Campylobacters
Campylobacters
Cayenne pepper (Capsicum frutescens)
- Solanaceae
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Cayenne pepper (Capsicum frutescens)
- Solanaceae
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Celiac disease
- Increased intestinal permeability appears secondary to the abnormal immune reaction induced by gluten
- Allows fragments of gliadin protein to get past the intestinal epithelium, triggering an immune response at the intestinal submucosa
- Leads to diverse gastrointestinal or extra-gastrointestinal symptoms
- Other environmental triggers may contribute to alter permeability in celiac disease
- Intestinal infections [1]
- Iron deficiency [1]
- Zhoršeno / vyvoláno / potencováno konzumpcí vitamínu C při doutnajícím zánětu /deficitu !!!
- Perpetuate a vicious circle [1]
- Eliminating gluten from the diet
- Normalization of intestinal permeability and the autoimmune process shuts off [1]
- Increase in permeability
- Sensitive test for the presence of even small amounts of gluten [4]
- In some studies gluten removal does not totally resolve the permeability
- Portion of the damage is irreversible
- Prior alteration in the tight junction [4]
- One third of first degree relatives had abnormal permeability [4]
- Cca 8% of these had a positive endomysial antibody test
- Underwent biopsy and asymptomatic coeliac diseas had been confirmed [4]
Celiac disease
- Increased intestinal permeability appears secondary to the abnormal immune reaction induced by gluten
- Allows fragments of gliadin protein to get past the intestinal epithelium, triggering an immune response at the intestinal submucosa
- Leads to diverse gastrointestinal or extra-gastrointestinal symptoms
- Other environmental triggers may contribute to alter permeability in celiac disease
- Intestinal infections [1]
- Iron deficiency [1]
- Zhoršeno / vyvoláno / potencováno konzumpcí vitamínu C při doutnajícím zánětu /deficitu !!!
- Perpetuate a vicious circle [1]
- Eliminating gluten from the diet
- Normalization of intestinal permeability and the autoimmune process shuts off [1]
- Increase in permeability
- Sensitive test for the presence of even small amounts of gluten [4]
- In some studies gluten removal does not totally resolve the permeability
- Portion of the damage is irreversible
- Prior alteration in the tight junction [4]
- One third of first degree relatives had abnormal permeability [4]
- Cca 8% of these had a positive endomysial antibody test
- Underwent biopsy and asymptomatic coeliac diseas had been confirmed [4]
Chemoterapie
Chemoterapie
Chitosan
- Polysaccharide widely used in the food industry
- Absorption-enhancing properties
- Caco-2 cells treated with chitosan have
- Altered distribution of ZO-1 and F-actin
- Increased paracellular permeability [11]
- Nano-based thiolated chitosan
- For enhancing permeability, mucoadhesivity and intestinal absorption
- Nanoparticles opened the tight junctions of monolayer Caco-2 cells
- Increased paracellular transportation
- Cascade of disruption of the TJ [12]
- Chitosan and over sulfated fucoidan
- Opened the TJ
- Induced redistribution of ZO-1 TJ protein [12]
- Potent paracellular permeation enhancer
- Induced clustering of integrin alpha (V) beta along the cell border
- Induced F-actin reorganization
- Claudin4 down-regulation
- Disrupting TJ integrity [12]
- Poly(lactic-co-glycolic acid) as carrier material
- Surface modified by methoxy poly(ethylene glycol) and chitosan
- Reduce the distribution of ZO-1 protein
- Impacting paracellular entry [12]
Chitosan
- Polysaccharide widely used in the food industry
- Absorption-enhancing properties
- Caco-2 cells treated with chitosan have
- Altered distribution of ZO-1 and F-actin
- Increased paracellular permeability [11]
- Nano-based thiolated chitosan
- For enhancing permeability, mucoadhesivity and intestinal absorption
- Nanoparticles opened the tight junctions of monolayer Caco-2 cells
- Increased paracellular transportation
- Cascade of disruption of the TJ [12]
- Chitosan and over sulfated fucoidan
- Opened the TJ
- Induced redistribution of ZO-1 TJ protein [12]
- Potent paracellular permeation enhancer
- Induced clustering of integrin alpha (V) beta along the cell border
- Induced F-actin reorganization
- Claudin4 down-regulation
- Disrupting TJ integrity [12]
- Poly(lactic-co-glycolic acid) as carrier material
- Surface modified by methoxy poly(ethylene glycol) and chitosan
- Reduce the distribution of ZO-1 protein
- Impacting paracellular entry [12]
Cholestáza
- Po zajištění vnitřní biliární drenáže se SP normalizuje [7]
Cholestáza
- Po zajištění vnitřní biliární drenáže se SP normalizuje [7]
Chronic liver diseases
- Are linked to increased IP [10]
Chronic liver diseases
- Are linked to increased IP [10]
Clostridia perfringens enterotoxin
Clostridia perfringens enterotoxin
Clostridium difficile
Clostridium difficile
Cow’s milk intolerance
Cow’s milk intolerance
Cremophor EL
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Cremophor EL
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Cronova choroba
- Unlikely to develop in susceptible animal models under germ free conditions [4]
- Several gene mutations have been identified
- NOD2/CARD1550
- Organic cation transporter (OCTN or IBD5) [4]
- NOD2/CARD15 variants involved in bacterial recognition
- Modulates both innate and adaptive immune responses
- Main susceptibility locus for CD development [16]
- Abnormal permeability is present prior to expression of the inflammatory disease
- Interleukin 10-/- mouse
- The SAMP mouse
- Mdra deficient mouse [4]
- Human increased small intestinal permeability
- Commonly observed in populations at high risk of developing Crohn's disease
- Impaired TJ complexity in sigmoid colon biopsies
- Reduced expression of sealing claudin-3, -5 and -8 and occludin [5]
- Re-distribution of claudin-5 and -8 off the TJ [5]
- Genes involved in autophagy like ATG16L1 and IRGM [16]
Cronova choroba
- Unlikely to develop in susceptible animal models under germ free conditions [4]
- Several gene mutations have been identified
- NOD2/CARD1550
- Organic cation transporter (OCTN or IBD5) [4]
- NOD2/CARD15 variants involved in bacterial recognition
- Modulates both innate and adaptive immune responses
- Main susceptibility locus for CD development [16]
- Abnormal permeability is present prior to expression of the inflammatory disease
- Interleukin 10-/- mouse
- The SAMP mouse
- Mdra deficient mouse [4]
- Human increased small intestinal permeability
- Commonly observed in populations at high risk of developing Crohn's disease
- Impaired TJ complexity in sigmoid colon biopsies
- Reduced expression of sealing claudin-3, -5 and -8 and occludin [5]
- Re-distribution of claudin-5 and -8 off the TJ [5]
- Genes involved in autophagy like ATG16L1 and IRGM [16]
CXCR3 receptors
- In cells in the intestinal epithelium respond to zonulin [1]
CXCR3 receptors
- In cells in the intestinal epithelium respond to zonulin [1]
Cyklofosfamid
- Týden po podání terapie statisticky význ. změny v SP [7]
Cyklofosfamid
- Týden po podání terapie statisticky význ. změny v SP [7]
Cytochalasin D
- Disrupt the cytoskeleton
- Inhibits ß- lactoglobulin–induced increases in TEER
Cytochalasin D
- Disrupt the cytoskeleton
- Inhibits ß- lactoglobulin–induced increases in TEER
Deficit
Deficit
Dermatitis herpetiformis (DH)
- From frank coeliac disease to a completely normal intestinal biopsy and no evidence of bowel disease [4]
- All had increased intestinal permeability [4]
- Elevated serum zonulin levels
- Some of these patients may go on to develop coeliac disease [4]
Dermatitis herpetiformis (DH)
- From frank coeliac disease to a completely normal intestinal biopsy and no evidence of bowel disease [4]
- All had increased intestinal permeability [4]
- Elevated serum zonulin levels
- Some of these patients may go on to develop coeliac disease [4]
Dextran sulfate sodium (DSS)
- Causes direct colonic epithelial cell injury and death [15]
- Used as model of colitis (inapropriate one) [15]
- Barrier loss is far greater in magnitude than that resulting from tight junction dysregulation
- DSS is an excellent model of acute intestinal damage
- Does not reflect IBD, IBS, or celiac disease
- Therapies effective in DSS colitis have failed in human IBD trials [15]
Dextran sulfate sodium (DSS)
- Causes direct colonic epithelial cell injury and death [15]
- Used as model of colitis (inapropriate one) [15]
- Barrier loss is far greater in magnitude than that resulting from tight junction dysregulation
- DSS is an excellent model of acute intestinal damage
- Does not reflect IBD, IBS, or celiac disease
- Therapies effective in DSS colitis have failed in human IBD trials [15]
Diabetes 1
- BB rat model of type 1 diabetes
- Provides strong support for increased permeability playing a key role in disease pathogenesis
- In humans, increases in intestinal permeability in type 1 diabetics
- First reported 20 years ago [4]
- Did not exclude patients with concomitant coeliac disease
- Did not use some of the more modern detection methods for the probes [4]
- More recent studies continue to find that type 1 diabetic patients have increased small intestinal permeability
- Not simply related to hyperglycaemia or poor glycaemic control [4]
- Patients with type 2 diabetes have normal permeability [4]
- Diabetic patients I.
- Had significantly higher serum zonulin levels than either controls or their relatives [4]
- “pre-diabetics”
- Positive for IA2 autoantibodies
- Before the onset of diabetes
- Elevated zonulin levels in seven of 10 specimens
- Increased permeability [4]
- The incidence of diabetes can be reduced in diabetes-prone rats
- By preventing an increase in epithelial permeability [11]
- Inhibitor AT1001 to BBDP rats
- Blocked autoantibody formation
- Blocked zonulin-induced increases in intestinal permeability
- Reducing the incidence of diabetes [11]
- 50% of T1D patients
- Elevated serum zonulin levels
- Elevated increased intestinal permeability [13]
- Delaying the exposure to diabetogenic wheat proteins
- By prolonging the breastfeeding period
- Reduced T1D development in the BBDP rats [13]
- Exposing neonatal rats or mice to diabetogenic wheat components or bacterial antigens
- Reduced T1D incidence
- Probably due to the induction of immunological tolerance [13]
Diabetes 1
- BB rat model of type 1 diabetes
- Provides strong support for increased permeability playing a key role in disease pathogenesis
- In humans, increases in intestinal permeability in type 1 diabetics
- First reported 20 years ago [4]
- Did not exclude patients with concomitant coeliac disease
- Did not use some of the more modern detection methods for the probes [4]
- More recent studies continue to find that type 1 diabetic patients have increased small intestinal permeability
- Not simply related to hyperglycaemia or poor glycaemic control [4]
- Patients with type 2 diabetes have normal permeability [4]
- Diabetic patients I.
- Had significantly higher serum zonulin levels than either controls or their relatives [4]
- “pre-diabetics”
- Positive for IA2 autoantibodies
- Before the onset of diabetes
- Elevated zonulin levels in seven of 10 specimens
- Increased permeability [4]
- The incidence of diabetes can be reduced in diabetes-prone rats
- By preventing an increase in epithelial permeability [11]
- Inhibitor AT1001 to BBDP rats
- Blocked autoantibody formation
- Blocked zonulin-induced increases in intestinal permeability
- Reducing the incidence of diabetes [11]
- 50% of T1D patients
- Elevated serum zonulin levels
- Elevated increased intestinal permeability [13]
- Delaying the exposure to diabetogenic wheat proteins
- By prolonging the breastfeeding period
- Reduced T1D development in the BBDP rats [13]
- Exposing neonatal rats or mice to diabetogenic wheat components or bacterial antigens
- Reduced T1D incidence
- Probably due to the induction of immunological tolerance [13]
DM2
- Patients were shown to have increased zonulin [10]
DM2
- Patients were shown to have increased zonulin [10]
E. coli endotoxin
E. coli endotoxin
Emulsifiers
- Induced alterations in intracellular events
- Destabilization of tight junctions between the GI epithelial cells
- Increasing intestinal leakage [12]
- Positive correlation:
- Annual sales of emulsifiers for food and beverage production
- Increased incidence of Crohn's disease [12]
- Emulsifier effects on breaching the integrity of the TJ
- Even at concentrations used in industrial food processing [12]
Self-microemulsifying systems
- Improve drug delivery via a microemulsion achieved by chemical
- Open the TJ
- Change the distribution of ZO-1 and actin
- Food applications are pending
- At nontoxic levels
- Paracellular flux increases [12]
Emulsifiers
- Induced alterations in intracellular events
- Destabilization of tight junctions between the GI epithelial cells
- Increasing intestinal leakage [12]
- Positive correlation:
- Annual sales of emulsifiers for food and beverage production
- Increased incidence of Crohn's disease [12]
- Emulsifier effects on breaching the integrity of the TJ
- Even at concentrations used in industrial food processing [12]
Self-microemulsifying systems
- Improve drug delivery via a microemulsion achieved by chemical
- Open the TJ
- Change the distribution of ZO-1 and actin
- Food applications are pending
- At nontoxic levels
- Paracellular flux increases [12]
Endotoxin E. coli
- Zvýšil po p.o. podání SP [7]
Endotoxin E. coli
- Zvýšil po p.o. podání SP [7]
Enteroinvasive E. coli (EIEC) strain O124:NM
- Induced loss of expression and redistribution of TJ-associated proteins
- Leads to the disruption and disorganization of the actin cytoskeleton
- Reversed by incubating the epithelial cells with L. plantarum
- Leads to a high density of actin filaments at the perijunctional regions
- TJ proteins being more closely associated with the cytoskeleton [11]
Enteroinvasive E. coli (EIEC) strain O124:NM
- Induced loss of expression and redistribution of TJ-associated proteins
- Leads to the disruption and disorganization of the actin cytoskeleton
- Reversed by incubating the epithelial cells with L. plantarum
- Leads to a high density of actin filaments at the perijunctional regions
- TJ proteins being more closely associated with the cytoskeleton [11]
Enzyme deficiency - intestinal secretion of lactase, sucrase, and maltase
- Decreased in conditions with intestinal mucosal injury and morphological changes
- Celiac disease
- Chronic diarrhea
Enzyme deficiency - intestinal secretion of lactase, sucrase, and maltase
- Decreased in conditions with intestinal mucosal injury and morphological changes
- Celiac disease
- Chronic diarrhea
Galangal (Alpinia officinarum)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Galangal (Alpinia officinarum)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Gastroenteritida
- Zvýšená SP korelovala s postižením sliznice [7]
- Incidence bakteriální translokace nekoreluje se zvýšením SP [7]
Gastroenteritida
- Zvýšená SP korelovala s postižením sliznice [7]
- Incidence bakteriální translokace nekoreluje se zvýšením SP [7]
Gelucire 44/14
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Gelucire 44/14
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Gliadin - gluten
- Activates zonulin signaling irrespective of the genetic expression of autoimmunity
- Increased intestinal permeability to macromolecules
- Trigger for zonulin release
- Subsequently increases paracellular permeability [4]
- MyD88 dependent
- Suggesting the involvement of a TLR pathway
- Interacts with the innate immune system through a TLR pathway
- Induces release of zonulin from a lamina propria source
- Increased paracellular movement of gluten
- Enhanced interaction of gluten with the mucosal immune system
- Initiating the inflammatory disease process [4]
- Gliadin stimulates zonulin signaling
- Leading to intestinal hyperpermeability [10]
- Gliadin causes zonulin release by binding to the CXCR3 receptor in intestinal cells [11]
- Cytotoxicity of gluten's main antigen, gliadin
- Gliadin
- Agglutinating activity
- Reduces F-actin content
- Inhibits cell growth
- Induces apoptosis
- Alters redox equilibrium
- Causes a rearrangement of the cytoskeleton
- Through the zonulin pathway
- Loss of TJ competence in the gastrointestinal mucosa [12]
- IEC6 and Caco-2 cells are exposed to gliadin in vitro
- Occludin - ZO-1 interaction is compromised
- Cytoskeleton is rearranged
- Increased monolayer permeability [12]
- Induces zonulin release
- Leading to PKC-mediated cytoskeletal reorganization
- Gliadin causes zonulin release
- By binding to the CXCR3 receptor in intestinal cells
- Via a MyD88-dependent pathway
- Subsequent transactivation of EGFR by PAR2
- Induces zonulin release from both intestinal cells and whole intestinal tissues
- Through CXCR3 binding
- gliadin-related EGF effects are secondary via zonulin [13]
- Chemokine receptor CXCR3 as the target intestinal receptor for gliadin
- Overexpressed in CD patients
- Recruitment of the adapter protein MyD88 to the receptor
- Crucial for the release of zonulin
- CXCR3-deficient mice
- Failed to respond to gliadin in terms of zonulin release and TJ disassembly [13]
Gliadin - gluten
- Activates zonulin signaling irrespective of the genetic expression of autoimmunity
- Increased intestinal permeability to macromolecules
- Trigger for zonulin release
- Subsequently increases paracellular permeability [4]
- MyD88 dependent
- Suggesting the involvement of a TLR pathway
- Interacts with the innate immune system through a TLR pathway
- Induces release of zonulin from a lamina propria source
- Increased paracellular movement of gluten
- Enhanced interaction of gluten with the mucosal immune system
- Initiating the inflammatory disease process [4]
- Gliadin stimulates zonulin signaling
- Leading to intestinal hyperpermeability [10]
- Gliadin causes zonulin release by binding to the CXCR3 receptor in intestinal cells [11]
- Cytotoxicity of gluten's main antigen, gliadin
- Gliadin
- Agglutinating activity
- Reduces F-actin content
- Inhibits cell growth
- Induces apoptosis
- Alters redox equilibrium
- Causes a rearrangement of the cytoskeleton
- Through the zonulin pathway
- Loss of TJ competence in the gastrointestinal mucosa [12]
- IEC6 and Caco-2 cells are exposed to gliadin in vitro
- Occludin - ZO-1 interaction is compromised
- Cytoskeleton is rearranged
- Increased monolayer permeability [12]
- Induces zonulin release
- Leading to PKC-mediated cytoskeletal reorganization
- Gliadin causes zonulin release
- By binding to the CXCR3 receptor in intestinal cells
- Via a MyD88-dependent pathway
- Subsequent transactivation of EGFR by PAR2
- Induces zonulin release from both intestinal cells and whole intestinal tissues
- Through CXCR3 binding
- gliadin-related EGF effects are secondary via zonulin [13]
- Chemokine receptor CXCR3 as the target intestinal receptor for gliadin
- Overexpressed in CD patients
- Recruitment of the adapter protein MyD88 to the receptor
- Crucial for the release of zonulin
- CXCR3-deficient mice
- Failed to respond to gliadin in terms of zonulin release and TJ disassembly [13]
Glucose
- Known as an absorption enhancer
- Major portion of intestinal glucose absorption occurs through tight junctions
- Not by saturable transcellular active transport !!! [12]
- Requires
- Increased junctional permeability
- High intraluminal glucose concentration
- Sufficient osmotic gradient [12]
- Increase permeability
- Produce changes in distribution of the main protein of TJ
- In the human cell line Caco-2 [12]
- Increase Caco-2 cell permeability
- Abnormal distribution of TJ proteins [12]
- Na+-glucose cotransport
- Activation of epithelial myosin light chain kinase (MLCK)
- Drives size-selective, i.e. pore pathway
- Increases in paracellular permeability
- Enhances pararcellular water flux
- Osmotic gradient created by transcellular Na+ and glucose transport
- Combination of paracellular water flow and increased paracellular permeability
- Paracellular absorption of nutrient-sized molecules
- Glucose
- Glucose
- Can reach very high concentrations within the unstirred layer
- Result of brush border digestive enzyme activity
- Carried passively as solutes within water
- Solvent drag
- Explains the inability of excess luminal glucose to saturate intestinal absorption !!!
- Contributes to the efficacy of Na+- and carbohydrate-based oral rehydration solutions !!!
Glucose
- Known as an absorption enhancer
- Major portion of intestinal glucose absorption occurs through tight junctions
- Not by saturable transcellular active transport !!! [12]
- Requires
- Increased junctional permeability
- High intraluminal glucose concentration
- Sufficient osmotic gradient [12]
- Increase permeability
- Produce changes in distribution of the main protein of TJ
- In the human cell line Caco-2 [12]
- Increase Caco-2 cell permeability
- Abnormal distribution of TJ proteins [12]
- Na+-glucose cotransport
- Activation of epithelial myosin light chain kinase (MLCK)
- Drives size-selective, i.e. pore pathway
- Increases in paracellular permeability
- Enhances pararcellular water flux
- Osmotic gradient created by transcellular Na+ and glucose transport
- Combination of paracellular water flow and increased paracellular permeability
- Paracellular absorption of nutrient-sized molecules
- Glucose
- Glucose
- Can reach very high concentrations within the unstirred layer
- Result of brush border digestive enzyme activity
- Carried passively as solutes within water
- Solvent drag
- Explains the inability of excess luminal glucose to saturate intestinal absorption !!!
- Contributes to the efficacy of Na+- and carbohydrate-based oral rehydration solutions !!!
Goblet cell-targeting CSK peptide
- Modified nanoparticles strongly opened epithelial TJ
- Via a C-Jun Nh2-terminal kinase-dependent pathway [12]
Goblet cell-targeting CSK peptide
- Modified nanoparticles strongly opened epithelial TJ
- Via a C-Jun Nh2-terminal kinase-dependent pathway [12]
Helikobacter pylori
Helikobacter pylori
Hops (Humulus lupulus)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Hops (Humulus lupulus)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Hydrogen peroxide
Hydrogen peroxide
Hypetermie malé pánve
- Zvýšená SP
Hypetermie malé pánve
- Zvýšená SP
IFN gamma
- Leads to a decrease in TEER
- An increase in epithelial permeability [11]
- Secondary to the inflammatory process
- Perpetuate the increased intestinal permeability
- By reorganizing TJ proteins
- ZO-1
- Junctional adhesion molecule 1
- Occludin
- Claudin-1
- Claudin-4 [13]
IFN gamma
- Leads to a decrease in TEER
- An increase in epithelial permeability [11]
- Secondary to the inflammatory process
- Perpetuate the increased intestinal permeability
- By reorganizing TJ proteins
- ZO-1
- Junctional adhesion molecule 1
- Occludin
- Claudin-1
- Claudin-4 [13]
IL-10 knockout
- Results in IBD etc. [15]
IL-10 knockout
- Results in IBD etc. [15]
IL-13
- Specifically increases flux across the pore pathway
- By upregulating expression of the tight junction protein claudin-2
- Forms a paracellular cation and water channel [15]
IL-13
- Specifically increases flux across the pore pathway
- By upregulating expression of the tight junction protein claudin-2
- Forms a paracellular cation and water channel [15]
Interleukin 2
- V terap. dávkách u onkol. onemocnění [7]
Interleukin 2
- V terap. dávkách u onkol. onemocnění [7]
IBS - irritable bowel syndrome
- Food hypersensitivity
- Some cases true food allergy
- Intestinal permeability pre and post provocation with suspect foods
- Developed abnormal permeability
- Concept of IBS developing
- Commonly observed following acute infectious gastroenteritis [4]
- Strongest association Campylobacter infections
- Increased permeability can be observed up to a year following infection
- IBS following a waterborne outbreak of gastroenteritis [4]
- Mucus layer becomes more permeable to bacteria
- Critical etiological factors in this disease [5]
IBS - irritable bowel syndrome
- Food hypersensitivity
- Some cases true food allergy
- Intestinal permeability pre and post provocation with suspect foods
- Developed abnormal permeability
- Concept of IBS developing
- Commonly observed following acute infectious gastroenteritis [4]
- Strongest association Campylobacter infections
- Increased permeability can be observed up to a year following infection
- IBS following a waterborne outbreak of gastroenteritis [4]
- Mucus layer becomes more permeable to bacteria
- Critical etiological factors in this disease [5]
L-alanine
- TJ permeability increase following l-alanine perfusion in rats [11]
L-alanine
- TJ permeability increase following l-alanine perfusion in rats [11]
Lactase (beta-galactosidase) deficiency
- More than half of the adult human population
- Lactase activity decreased significantly with age
- Correlated with degree of intestinal injury
- Lactose intolerance
- Abdominal pain, bloating, diarrhea
- Increased breath hydrogen excretion
- Fungal lactase p.o. or added to milk at mealtime
- Effective at preventing or reducing signs and symptoms [14]
Lactase (beta-galactosidase) deficiency
- More than half of the adult human population
- Lactase activity decreased significantly with age
- Correlated with degree of intestinal injury
- Lactose intolerance
- Abdominal pain, bloating, diarrhea
- Increased breath hydrogen excretion
- Fungal lactase p.o. or added to milk at mealtime
- Effective at preventing or reducing signs and symptoms [14]
Lektiny
- Sprouting and fermenting grains reduces phytates and lectins
- Making these foods easier to digest
- GMO and hybridized foods
- Tend to be the highest in lectins
- Since they have been modified to fight off bugs [20]
Lektiny
- Sprouting and fermenting grains reduces phytates and lectins
- Making these foods easier to digest
- GMO and hybridized foods
- Tend to be the highest in lectins
- Since they have been modified to fight off bugs [20]
Maraton
- Zvýšení SP u běžců LA/MA testem
- Profylaxe vit. A bez efektu [7]
- Ibuprofen zvýšil SP [7]
- Aspirin bez efektu [7]
Maraton
- Zvýšení SP u běžců LA/MA testem
- Profylaxe vit. A bez efektu [7]
- Ibuprofen zvýšil SP [7]
- Aspirin bez efektu [7]
Marigold (Tagetes erecta)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Marigold (Tagetes erecta)
- Decrease TEER
- Increase paracellular flux of Lucifer yellow across Caco-2 monolayers
- Without having any cytotoxic effect on the cells [11]
Medium-chain fatty acids
- Capric acid
- Lauric acid
- Increase paracellular flux
- Cause a rapid decrease in TEER in Caco-2 cells [11]
Medium-chain fatty acids
- Capric acid
- Lauric acid
- Increase paracellular flux
- Cause a rapid decrease in TEER in Caco-2 cells [11]
Melanom v pokročilém stavu
Melanom v pokročilém stavu
Melfalan
- Zvýšené střevní propustnosti tímto lékem lze zabránit profylaktickým podáním cyklofosfamidu [7]
Melfalan
- Zvýšené střevní propustnosti tímto lékem lze zabránit profylaktickým podáním cyklofosfamidu [7]
Methanol
- Increase permeability
- Disturb TJ protein arrangement in the Caco-2 model [12]
Methanol
- Increase permeability
- Disturb TJ protein arrangement in the Caco-2 model [12]
Metotrexát
- Inhibition of DHFR
- Can also inbibit de novo purine synthesis
- MTX treatment can lead to the inhibition of DNA and RNA synthesis
- Even to inhibition of protein synthesis in tumor tissue as well as normal tissue.
- Block thymidylate biosynthesis and thus DNA synthesis
- MTX and other folate antagonists are extremely toxic to rapidly proliferating tissues
- Tumor tissue
- Bone marrow
- The small intestinal epithelium
- Often limits the clinical application [22]
- Induce loss of crypts, crypt atrophy, and villus atrophy [22]
- Down-regulation of SI and lactase enzyme activities [22]
Metotrexát
- Inhibition of DHFR
- Can also inbibit de novo purine synthesis
- MTX treatment can lead to the inhibition of DNA and RNA synthesis
- Even to inhibition of protein synthesis in tumor tissue as well as normal tissue.
- Block thymidylate biosynthesis and thus DNA synthesis
- MTX and other folate antagonists are extremely toxic to rapidly proliferating tissues
- Tumor tissue
- Bone marrow
- The small intestinal epithelium
- Often limits the clinical application [22]
- Induce loss of crypts, crypt atrophy, and villus atrophy [22]
- Down-regulation of SI and lactase enzyme activities [22]
Metronidazole
- Increase the inflammatory tone of the intestine
- Linked to a disruption of the microbiota [25]
Metronidazole
- Increase the inflammatory tone of the intestine
- Linked to a disruption of the microbiota [25]
Microbial transglutaminase (mTG)
- Extracellular enzyme:
- Acyl-transfer reaction
- Cross-linking reaction between Gln and Lys residues of proteins or peptides (transamidation)
- Deamidation [12]
- Biosynthesized by several microbes
- Isolated from Streptoverticillium sp.
- Microbial TG
- Modifying the functionality of proteins in food products [12]
- Can have protective and trophic functions like human TG on infectious agents
- Facilitates their survival in the gut lumen
- Tight junction may leak since infections increase intestinal permeability
- Deprivation of glutamine (Gln) from cell culture medium
- Significant decreases in transepithelial resistance of Caco-2 cell monolayers
- Increased permeability
- Can induce AMK imbalnace: glutamine deprivation/surfur plus
- Zvýšená SP [12]
- Cross-linking of different proteins
- Major modifier of the physical and chemical properties and structure
- New nutritional immunogenic epitopes
- Meat products have been found to contain variable amounts of mTG
- MTG has emulsifying properties by cross-linking different proteins
- MTG has the ability to catalyze lipidation of protein
- Providing them with emulsifying activity [12]
- MTG induced cross-linking of various dietary proteins originating from casein, pork myofibrils, peanut and fish [12]
- Shown to improve their emulsifying capacity [12]
- Hydrolyzed gluten by itself improves emulsification, regardless of mTG treatment [12]
- Nanoparticle cross-linking
- Designing new luminal delivery systems [12]
- Multiple mTG linked proteins
- Bakery products
- Immunogenic to celiac disease patients !!!
- Mají protilátky i proti transglutamináze nejen proti lepku !!!
- Specific anti-mTG and mTG-gliadin neo complex antibodies
- Only in CD sera
- Not in healthy controls [12]
Microbial transglutaminase (mTG)
- Extracellular enzyme:
- Acyl-transfer reaction
- Cross-linking reaction between Gln and Lys residues of proteins or peptides (transamidation)
- Deamidation [12]
- Biosynthesized by several microbes
- Isolated from Streptoverticillium sp.
- Microbial TG
- Modifying the functionality of proteins in food products [12]
- Can have protective and trophic functions like human TG on infectious agents
- Facilitates their survival in the gut lumen
- Tight junction may leak since infections increase intestinal permeability
- Deprivation of glutamine (Gln) from cell culture medium
- Significant decreases in transepithelial resistance of Caco-2 cell monolayers
- Increased permeability
- Can induce AMK imbalnace: glutamine deprivation/surfur plus
- Zvýšená SP [12]
- Cross-linking of different proteins
- Major modifier of the physical and chemical properties and structure
- New nutritional immunogenic epitopes
- Meat products have been found to contain variable amounts of mTG
- MTG has emulsifying properties by cross-linking different proteins
- MTG has the ability to catalyze lipidation of protein
- Providing them with emulsifying activity [12]
- MTG induced cross-linking of various dietary proteins originating from casein, pork myofibrils, peanut and fish [12]
- Shown to improve their emulsifying capacity [12]
- Hydrolyzed gluten by itself improves emulsification, regardless of mTG treatment [12]
- Nanoparticle cross-linking
- Designing new luminal delivery systems [12]
- Multiple mTG linked proteins
- Bakery products
- Immunogenic to celiac disease patients !!!
- Mají protilátky i proti transglutamináze nejen proti lepku !!!
- Specific anti-mTG and mTG-gliadin neo complex antibodies
- Only in CD sera
- Not in healthy controls [12]
Mastné kyseliny - fatty acids
- Oleic
- Docosahexaenoic acids
- EPA
- DHA
- Gamma-LA
- Capric
- Lauric acid [12]
- Surface active compounds
- Compromised the integrity of the intestinal epithelium
- Enhanced the paracellular absorption of poorly absorbed hydrophilic substances
- Increase TJ permeability [12]
Mastné kyseliny - fatty acids
- Oleic
- Docosahexaenoic acids
- EPA
- DHA
- Gamma-LA
- Capric
- Lauric acid [12]
- Surface active compounds
- Compromised the integrity of the intestinal epithelium
- Enhanced the paracellular absorption of poorly absorbed hydrophilic substances
- Increase TJ permeability [12]
MLCK - myosin light chain kinase activation
- MLCK fosforyluje regulatory myosin light chain (MLC) II
- MLC phosphorylation
- Contractions in the actomyosin ring
- Increases in TJ permeability [11]
- Initiation of Na+-glucose cotransport
- Followed by increased phosphorylation of MLC
- Inhibition of MLCK
- Prevents increases in TJ permeability
- MLCK-mediated regulation of TJ permeability
- Crucial intermediate step in a variety of pathways
- Cytokines
- Bacteria [11]
MLCK - myosin light chain kinase activation
- MLCK fosforyluje regulatory myosin light chain (MLC) II
- MLC phosphorylation
- Contractions in the actomyosin ring
- Increases in TJ permeability [11]
- Initiation of Na+-glucose cotransport
- Followed by increased phosphorylation of MLC
- Inhibition of MLCK
- Prevents increases in TJ permeability
- MLCK-mediated regulation of TJ permeability
- Crucial intermediate step in a variety of pathways
- Cytokines
- Bacteria [11]
Mucosal oxidative stress
Mucosal oxidative stress
N-cadherin mutace
- Abnormal function of intercellular junctions
- Mucosal inflammatory disorder that resembled Crohn's disease [3]
N-cadherin mutace
- Abnormal function of intercellular junctions
- Mucosal inflammatory disorder that resembled Crohn's disease [3]
N-cadherin mutant in epithelial cells along the crypt-villus axis
- Induced abnormal function of intercellular junctions
- Initiated a mucosal inflammatory disorder
- Resembled Crohn's disease
N-cadherin mutant in epithelial cells along the crypt-villus axis
- Induced abnormal function of intercellular junctions
- Initiated a mucosal inflammatory disorder
- Resembled Crohn's disease
Na-cholate
- Additional absorption enhancer
- Disturb TJ protein distribution
- Increased Caco-2 inter-cell permeability [12]
Na-cholate
- Additional absorption enhancer
- Disturb TJ protein distribution
- Increased Caco-2 inter-cell permeability [12]
Nádorové onemocnění ledvin
Nádorové onemocnění ledvin
Nanoparticles
- Surfactants, polymers, chelating agents
- Mainly the small size lipid nanoparticles
- May increase the gap dimensions of TJ [12]
- Health concerns associated with increasing the oral bioavailability of bioactive components [12]
Nanoparticles
- Surfactants, polymers, chelating agents
- Mainly the small size lipid nanoparticles
- May increase the gap dimensions of TJ [12]
- Health concerns associated with increasing the oral bioavailability of bioactive components [12]
Necrotizing enterocolitis
Necrotizing enterocolitis
NOD2/CARD15 gene mutation
- Riziko Cronovy choroby [4]
NOD2/CARD15 gene mutation
- Riziko Cronovy choroby [4]
NOD2 mutation
- Increased among first degree relatives of those with Crohn's disease [4] [15]
- Relatives with a NOD2 mutation had a 75% chance of having increased permeability [4]
- Reflects subclinical immune activation [15]
- NOD2 gene product is present in Paneth cells
- Mutation is associated with a reduction in secretion of defensins [4]
NOD2 mutation
- Increased among first degree relatives of those with Crohn's disease [4] [15]
- Relatives with a NOD2 mutation had a 75% chance of having increased permeability [4]
- Reflects subclinical immune activation [15]
- NOD2 gene product is present in Paneth cells
- Mutation is associated with a reduction in secretion of defensins [4]
NSAIDs - NAF
- Hyperresponsiveness of the small intestine to the damaging effects [4] [16]
- Aspirin
- Ibuprofen [4]
NSAIDs - NAF
- Hyperresponsiveness of the small intestine to the damaging effects [4] [16]
- Aspirin
- Ibuprofen [4]
Obstructive jaundice
Obstructive jaundice
Opportunistically invasive commensal bacteria:
- Salmonella enterica Serovar Typhimurium (Salmonella typhimurium)
- Enterococcus faecalis
- Candidae etc.
Opportunistically invasive commensal bacteria:
- Salmonella enterica Serovar Typhimurium (Salmonella typhimurium)
- Enterococcus faecalis
- Candidae etc.
Organic solvents
- Associated with
- Systemic sclerosis
- Primary systemic vasculitis
- Multiple sclerosis
- Ost. autoimunity
- Premeabilita GIT [12]
Organic solvents
- Associated with
- Systemic sclerosis
- Primary systemic vasculitis
- Multiple sclerosis
- Ost. autoimunity
- Premeabilita GIT [12]
Pancreatic insufficiency
- Insufficient pancreatic enzyme activity
- Can cause increased IP and leaky gut syndrome [14]
- Supplementation with digestive enzymes can
- Help to treat enzyme deficiencies
- Improve conditions related to impaired digestion [14]
Pankreatické enzymy lze supplementovat
- Exposure to gastric acid can destroy
- Up to 90% of supplemental pancreatic lipase
- 65% of pancreatic trypsin
- Enteric coatings
- May not dissolve reliably in all cases
- Some patients are unable to concentrate bicarbonate sufficiently to alkalinize the upper small intestine for normal release of enteric coatings
- Resulting in jejunal hyperactivity
- Can also inhibit pancreatic enzyme activity even if enteric coatings do dissolve as intended [14]
- Acid-stable fungal enzyme preparations
- Stable and active in both acid and alkaline pH conditions
- Effective without the need for enteric coatings or coadministration of pH-altering drugs
- Acid-stable fungal lipase
- Effective at a substantially lower dose than pancreatin in reducing steatorrhea and relieving symptoms of diarrhea and digestive discomfort [14]
Pancreatic insufficiency
- Insufficient pancreatic enzyme activity
- Can cause increased IP and leaky gut syndrome [14]
- Supplementation with digestive enzymes can
- Help to treat enzyme deficiencies
- Improve conditions related to impaired digestion [14]
Pankreatické enzymy lze supplementovat
- Exposure to gastric acid can destroy
- Up to 90% of supplemental pancreatic lipase
- 65% of pancreatic trypsin
- Enteric coatings
- May not dissolve reliably in all cases
- Some patients are unable to concentrate bicarbonate sufficiently to alkalinize the upper small intestine for normal release of enteric coatings
- Resulting in jejunal hyperactivity
- Can also inhibit pancreatic enzyme activity even if enteric coatings do dissolve as intended [14]
- Acid-stable fungal enzyme preparations
- Stable and active in both acid and alkaline pH conditions
- Effective without the need for enteric coatings or coadministration of pH-altering drugs
- Acid-stable fungal lipase
- Effective at a substantially lower dose than pancreatin in reducing steatorrhea and relieving symptoms of diarrhea and digestive discomfort [14]
Pankreatitida
- Zvýšení SP
Pankreatitida
- Zvýšení SP
Paprika (Capsicum anuum)
- Solanaceae
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Paprika (Capsicum anuum)
- Solanaceae
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Paradichlorobenzene
- Toilet cleaner
- Induce leucoencephalopathy
- Deterioration in multiple sclerosis patients [12]
Paradichlorobenzene
- Toilet cleaner
- Induce leucoencephalopathy
- Deterioration in multiple sclerosis patients [12]
Parasites
Parasites
Parenterální výživa totální
- Vede ke snížení klků [7]
- Ke zvýšení SP [7]
- Předchází se
- Podáním glutaminu do i.v. výživy [7]
- Enterální výživa alespoň malé množství [7]
- Přidání BCAA bylo v někt. studích bez efektu na SP [7]
- 5 denní hladovka neměla efekt na SP [7]
Parenterální výživa totální
- Vede ke snížení klků [7]
- Ke zvýšení SP [7]
- Předchází se
- Podáním glutaminu do i.v. výživy [7]
- Enterální výživa alespoň malé množství [7]
- Přidání BCAA bylo v někt. studích bez efektu na SP [7]
- 5 denní hladovka neměla efekt na SP [7]
Phytase deficiency
- Bioavailability of minerals can be considerably reduced by dietary phytate
- Humans and monogastric animals produce little or no endogenous phytase in the stomach and small intestine
- Dietary supplementation with an acid-stable fungal phytase from Aspergillus niger
- Increased iron absorption
- Fungal phytase was stable and active across a broad pH range from 1.0 to 7.5
- Initiated digestion of dietary phytate beginning in the stomach
- Helped to improve zinc, calcium, and phosphorus bioavailability
- Increase bone strength in a dose-dependent manner [14]
- Helps to increase nutritional value of dietary grains in animals
- Improved digestibility of dietary cell wall components
- Increased solubility of calcium, phosphorus, iron, zinc, and copper associated with cell walls [14]
Phytase deficiency
- Bioavailability of minerals can be considerably reduced by dietary phytate
- Humans and monogastric animals produce little or no endogenous phytase in the stomach and small intestine
- Dietary supplementation with an acid-stable fungal phytase from Aspergillus niger
- Increased iron absorption
- Fungal phytase was stable and active across a broad pH range from 1.0 to 7.5
- Initiated digestion of dietary phytate beginning in the stomach
- Helped to improve zinc, calcium, and phosphorus bioavailability
- Increase bone strength in a dose-dependent manner [14]
- Helps to increase nutritional value of dietary grains in animals
- Improved digestibility of dietary cell wall components
- Increased solubility of calcium, phosphorus, iron, zinc, and copper associated with cell walls [14]
Podvýživa
- Vázne resorpce mannitolu (transepiteliální transport)
- Snížení vilózních klků [7]
- Zvýšení SP
Podvýživa
- Vázne resorpce mannitolu (transepiteliální transport)
- Snížení vilózních klků [7]
- Zvýšení SP
Polymers natural and synthetic
- Polymer
- Synthetic lipid-polymer
- Increased TJ permeability in a surface charge depended way
- Electrostatic interactions with the TJ proteins [12]
Polymers natural and synthetic
- Polymer
- Synthetic lipid-polymer
- Increased TJ permeability in a surface charge depended way
- Electrostatic interactions with the TJ proteins [12]
Popáleniny
- Zvýšená SP [7] pro oligosacharidy i EDTA
- Hlavní příčina septických stavů [7]
Popáleniny
- Zvýšená SP [7] pro oligosacharidy i EDTA
- Hlavní příčina septických stavů [7]
Prednisone
- [26]
Prednisone
- [26]
Prematurity
Prematurity
Prokrvení a okysličení střeva snížené
- Kritické stavy se sníženou perfúzí a oxygenací
- Endotoxemie
- Těžké OP s poklesem perfúze / s hypovolémií
- Prevencí dekontaminace střevního obsahu
- Sníží bakteriální translokaci i přestup endotoxinů [7]
- Zvýšení SP
- Zvýšeným prostupem makromolekulárních látek [7]
- Paracelulárně
- Translokace bakterií
- V.s. transcelulárně [7]
- Tíže SP koreluje po 76-96h s tíží traumatu
- Zvýšení koreluje s rozvojem multiorgánového selhání
- Laktulóza mannitol test [7]
Ischemie střeva
- Zvýšená SP
- Nekoreluje s tíží sepse či šoku [7]
Prokrvení a okysličení střeva snížené
- Kritické stavy se sníženou perfúzí a oxygenací
- Endotoxemie
- Těžké OP s poklesem perfúze / s hypovolémií
- Prevencí dekontaminace střevního obsahu
- Sníží bakteriální translokaci i přestup endotoxinů [7]
- Zvýšení SP
- Zvýšeným prostupem makromolekulárních látek [7]
- Paracelulárně
- Translokace bakterií
- V.s. transcelulárně [7]
- Tíže SP koreluje po 76-96h s tíží traumatu
- Zvýšení koreluje s rozvojem multiorgánového selhání
- Laktulóza mannitol test [7]
Ischemie střeva
- Zvýšená SP
- Nekoreluje s tíží sepse či šoku [7]
Proton pump blockers
Proton pump blockers
Psychological stress
- Předchází relapsům Crohnovy choroby
- Induce intestinal barrier loss in rodents [15]
- Through the release of corticotropin-releasing factors [16]
Psychological stress
- Předchází relapsům Crohnovy choroby
- Induce intestinal barrier loss in rodents [15]
- Through the release of corticotropin-releasing factors [16]
PUFA
- DHA
- ?-linolenic acid
- EPA
- Decrease TEER
- Increase paracellular permeability of fluorescein sulfonic acid
- In a concentration-dependent manner [11]
PUFA
- DHA
- ?-linolenic acid
- EPA
- Decrease TEER
- Increase paracellular permeability of fluorescein sulfonic acid
- In a concentration-dependent manner [11]
Quillaja saponin
- At nontoxic levels
- TEER decreases
- Paracellular flux increases [11]
Quillaja saponin
- At nontoxic levels
- TEER decreases
- Paracellular flux increases [11]
Radioterapie
- Radiation to the abdomen, pelvis, or rectum
- Acute enteritis, which is dose limiting [21]
- 5% to 15% of them will develop chronic problems [21]
- Nejcitlivější duodenum [7]
1. změny - Early radiation enteropathy
- During or shortly after radiotherapy
- Death of rapidly proliferating crypt cells
- Epithelial barrier breakdown
- Inflammation (radiation mucositis)
- Zrychluje se peristaltika
- Vznik edemu
- Následně vředovité léze sliznice
- Průjem, bolesti břicha ev. až dehydratace či malabsorpce [7]
2. pozdní změny - Delayed radiation enteropathy
- Intestinal dysfunction
- Associated with vascular sclerosis
- Progressive intestinal wall fibrosis
- Complex interplay of various cell types, factors, and extracellular matrix
- Cca za 6-18 měs.
- Chronické vředy
- Ileus z poškození nervově-cévních pletení
- Fibritické srůsty
- 6-12 měs. po ozáření břicha pro maligní nádor
- Zvýšení SP pro cheláty = x střevní sliznice
- St. p. ozařování malé pánve po 15 dnech ter.
- Zvýšená SP pro cellobiozu/mannitol
- Ke konci radioterapie se hodnoty normalizovaly [7]
Radiosenzitivita
- Radiosensitive tissues tend to have high levels of p53 activity and induction of apoptosis and apoptotic targets [21]
- Loss of p53 in intestine exacerbates GI damage and accelerated GI syndrome [21]
Radioprotektivní látky
- Velká kapitola mnoha dalších... zde není prostor
- Ok efekt probiotik po radioterapii při rotavirovém průjmu [7]
- glutamin p.o.
- Při chemoterapii (fluorouracil, cisplatina) + radioterapie mediastina
- Protektivně na počet lymfocytů a SP [7]
- Loss of p53
- Protects the hematopoietic (HP) system and skin against IR and chemotherapy-induced injuries (56,57), and the small intestine from chemotherapy-induced apoptosis and mucositis
Radioterapie
- Radiation to the abdomen, pelvis, or rectum
- Acute enteritis, which is dose limiting [21]
- 5% to 15% of them will develop chronic problems [21]
- Nejcitlivější duodenum [7]
1. změny - Early radiation enteropathy
- During or shortly after radiotherapy
- Death of rapidly proliferating crypt cells
- Epithelial barrier breakdown
- Inflammation (radiation mucositis)
- Zrychluje se peristaltika
- Vznik edemu
- Následně vředovité léze sliznice
- Průjem, bolesti břicha ev. až dehydratace či malabsorpce [7]
2. pozdní změny - Delayed radiation enteropathy
- Intestinal dysfunction
- Associated with vascular sclerosis
- Progressive intestinal wall fibrosis
- Complex interplay of various cell types, factors, and extracellular matrix
- Cca za 6-18 měs.
- Chronické vředy
- Ileus z poškození nervově-cévních pletení
- Fibritické srůsty
- 6-12 měs. po ozáření břicha pro maligní nádor
- Zvýšení SP pro cheláty = x střevní sliznice
- St. p. ozařování malé pánve po 15 dnech ter.
- Zvýšená SP pro cellobiozu/mannitol
- Ke konci radioterapie se hodnoty normalizovaly [7]
Radiosenzitivita
- Radiosensitive tissues tend to have high levels of p53 activity and induction of apoptosis and apoptotic targets [21]
- Loss of p53 in intestine exacerbates GI damage and accelerated GI syndrome [21]
Radioprotektivní látky
- Velká kapitola mnoha dalších... zde není prostor
- Ok efekt probiotik po radioterapii při rotavirovém průjmu [7]
- glutamin p.o.
- Při chemoterapii (fluorouracil, cisplatina) + radioterapie mediastina
- Protektivně na počet lymfocytů a SP [7]
- Loss of p53
- Protects the hematopoietic (HP) system and skin against IR and chemotherapy-induced injuries (56,57), and the small intestine from chemotherapy-induced apoptosis and mucositis
Reakce štěpu proti hostiteli
- Po transplantaci kostní dřeně
- P.o. podaný IgA-IgG ochranný vliv a upravuje SP dle 51Cr-EDTA [7]
- Dg. rejekce transplantátu tenkého střeva
Reakce štěpu proti hostiteli
- Po transplantaci kostní dřeně
- P.o. podaný IgA-IgG ochranný vliv a upravuje SP dle 51Cr-EDTA [7]
- Dg. rejekce transplantátu tenkého střeva
Refined sugars
- "Western diet with its high content of fat and is a risk factor for the development of CD probably inducing a low-grade inflammation via gut dysbiosis and increased intestinal permeability." [16]
Refined sugars
- "Western diet with its high content of fat and is a risk factor for the development of CD probably inducing a low-grade inflammation via gut dysbiosis and increased intestinal permeability." [16]
Rheumatological conditions
- Associated with abnormalities of intestinal function
- Abnormal reactivity to a luminal antigen in these conditions is prevalent
- Ankylosing spondylitis
- Increased gastrointestinal permeability present in these patients for decades
- Unclear whether this was due to the disease or its treatment with NSAIDs
- Appear to have a primary defect in intestinal permeability
- Also shared by a subgroup of relatives [4]
- Permeability defect was limited to the small intestine
- Not expressed in the stomach
- Ankylosing spondylitis and Helicobacter pylori infection
- Have increased gastric permeability
- Eradicated
- Increased gastric permeability to sucrose fell in non-arthritic patients
- Remained elevated in those suffering from spondylitis [4]
- V.s. pre-existing increase in gastric permeability [4]
Rheumatological conditions
- Associated with abnormalities of intestinal function
- Abnormal reactivity to a luminal antigen in these conditions is prevalent
- Ankylosing spondylitis
- Increased gastrointestinal permeability present in these patients for decades
- Unclear whether this was due to the disease or its treatment with NSAIDs
- Appear to have a primary defect in intestinal permeability
- Also shared by a subgroup of relatives [4]
- Permeability defect was limited to the small intestine
- Not expressed in the stomach
- Ankylosing spondylitis and Helicobacter pylori infection
- Have increased gastric permeability
- Eradicated
- Increased gastric permeability to sucrose fell in non-arthritic patients
- Remained elevated in those suffering from spondylitis [4]
- V.s. pre-existing increase in gastric permeability [4]
Rho kinases (ROCK)
- Phosphorylate MLC
- Induce contraction of the actomyosin ring
- Premability + [11]
- Inhibition of ROCK
- Prevents proper localization of TJ proteins during TJ assembly in cultured T84 monolayers [11]
- Redistribution of ZO-1 and occludin away from the cell membrane
- Reorganization of perijunctional F-actin
- Reduced TEER
- Increased paracellular flux
- Increased activation of Rho
- Can also lead to increased TJ disassembly
- Via contraction of the actomyosin ring
- Induced by increased Rho/ROCK signaling
- Increased MLC phosphorylation [11]
Rho kinases (ROCK)
- Phosphorylate MLC
- Induce contraction of the actomyosin ring
- Premability + [11]
- Inhibition of ROCK
- Prevents proper localization of TJ proteins during TJ assembly in cultured T84 monolayers [11]
- Redistribution of ZO-1 and occludin away from the cell membrane
- Reorganization of perijunctional F-actin
- Reduced TEER
- Increased paracellular flux
- Increased activation of Rho
- Can also lead to increased TJ disassembly
- Via contraction of the actomyosin ring
- Induced by increased Rho/ROCK signaling
- Increased MLC phosphorylation [11]
Salmonella lacking AvrA
- Leads to the disruption of TJ
- Reduced expression of TJ proteins
- Disorganized expression [11]
Salmonella lacking AvrA
- Leads to the disruption of TJ
- Reduced expression of TJ proteins
- Disorganized expression [11]
Salt
- Excess uptake of salt can affect the innate immune system
- Macrophage function
- Differentiation of naive CD4 + T cells into a greater number of TH17 cells
- High salt concentration
- Change in osmolarity
- Influence of IL-23 and IL-23 receptor signaling
- Activation of various enzymes
- Drive the expression of TH17-associated cytokines
- Formation of the pathogenic TH17 phenotype
- Role in autoimmune disease
- Neuropathy in a mouse model [12]
- Multiple sclerosis [12]
- Initiation of Na+-glucose cotransport
- Activation of NHE3
- A major route of Na+ absorption in the small intestine
- Increased phosphorylation of myosin light chain
- Contraction of the perijunctional actomyosin ring
- Increased permeability of intestinal tight junctions [12]
- Paracellular Na+ flow associated nutrient transport was elucidated
Salt
- Excess uptake of salt can affect the innate immune system
- Macrophage function
- Differentiation of naive CD4 + T cells into a greater number of TH17 cells
- High salt concentration
- Change in osmolarity
- Influence of IL-23 and IL-23 receptor signaling
- Activation of various enzymes
- Drive the expression of TH17-associated cytokines
- Formation of the pathogenic TH17 phenotype
- Role in autoimmune disease
- Neuropathy in a mouse model [12]
- Multiple sclerosis [12]
- Initiation of Na+-glucose cotransport
- Activation of NHE3
- A major route of Na+ absorption in the small intestine
- Increased phosphorylation of myosin light chain
- Contraction of the perijunctional actomyosin ring
- Increased permeability of intestinal tight junctions [12]
- Paracellular Na+ flow associated nutrient transport was elucidated
Saponin
- At nontoxic levels
- Paracellular flux increases [12]
Saponin
- At nontoxic levels
- Paracellular flux increases [12]
Sarkoidóza
- Zvýšení SP v aktivním stadiu [7]
- V klidovém stadiu SP v normě [7]
Sarkoidóza
- Zvýšení SP v aktivním stadiu [7]
- V klidovém stadiu SP v normě [7]
SGLT1 aktivace
- Activation of the sodium dependent glucose transporter
- Physiological opening of tight junctions
- Allows for the movement of small molecules and peptides [3]
- Sizes of the order of 2000 molecular weight (MW)
- Still exclude large particles such as horseradish peroxidase (MW 40 000) [3]
SGLT1 aktivace
- Activation of the sodium dependent glucose transporter
- Physiological opening of tight junctions
- Allows for the movement of small molecules and peptides [3]
- Sizes of the order of 2000 molecular weight (MW)
- Still exclude large particles such as horseradish peroxidase (MW 40 000) [3]
Small bowel/intestine bacterial overgrowth - SIBO
- Or dysbiosis
- May contribute substantially to local chronic inflammation [18]
- May provoke bacterial translocation [18]
Small bowel/intestine bacterial overgrowth - SIBO
- Or dysbiosis
- May contribute substantially to local chronic inflammation [18]
- May provoke bacterial translocation [18]
Sodium caprate
- Mildly damaging agent
- Non-inflamed tissue demonstrated a marked increase in paracellular permeability [4]
- Irregular expression of ZO-1 and occludin at the cell boundaries [11]
- Decrease in paracellular permeability was observed within 3 min of capric acid exposure
- Reorganization of TJ proteins took at least 60 min
- In rat ileum ex vivo
- Increase TJ permeability
- Reducing TEER
- Increasing parcellular flux
- Inducing dilations in TJ visible by transmission electron microscopy [11]
Sodium caprate
- Mildly damaging agent
- Non-inflamed tissue demonstrated a marked increase in paracellular permeability [4]
- Irregular expression of ZO-1 and occludin at the cell boundaries [11]
- Decrease in paracellular permeability was observed within 3 min of capric acid exposure
- Reorganization of TJ proteins took at least 60 min
- In rat ileum ex vivo
- Increase TJ permeability
- Reducing TEER
- Increasing parcellular flux
- Inducing dilations in TJ visible by transmission electron microscopy [11]
Sodium taurocholate
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Sodium taurocholate
- Surfactants
- Used in pharmaceutical and food industries
- Disrupt the intestinal barrier
Šokové stavy
- Translokace bakterií a jejich toxinů
- Může být poslední fází fatální sepse aj. těžkého stavu
- Acute pancreatitis [16]
- Multiple organ failure [16]
- Major surgery [16]
- Severe trauma [16]
- Could explain the high prevalence of Gram-negative sepsis
- And related mortality in critically ill patients [16]
Šokové stavy
- Translokace bakterií a jejich toxinů
- Může být poslední fází fatální sepse aj. těžkého stavu
- Acute pancreatitis [16]
- Multiple organ failure [16]
- Major surgery [16]
- Severe trauma [16]
- Could explain the high prevalence of Gram-negative sepsis
- And related mortality in critically ill patients [16]
Solanaceae spices - cayenne pepper (Capsicum frutescens) and paprika (Capsicum anuum)
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Solanaceae spices - cayenne pepper (Capsicum frutescens) and paprika (Capsicum anuum)
- Immediate decrease in TEER in vitro in the ileocecal adenocarcinoma cell line HCT-8
- Paprika
- Accompanied by an increase in small molecule permeability
- Aberrant staining of ZO-1 [11]
- Capsianoside
- Reorganize actin filaments and decrease TEER [11]
Sucrose monoester fatty acid
- Food-grade surfactant
- Decrease in TEER [11]
- An increase in the permeability of the egg white allergen ovomucoid across Caco-2 monolayers [11]
- Perijuntional rings were partially disbanded [11]
- Major and potent surfactants used in the food industry
- Induced actin disbandment and structural separation of TJ in Caco-2 cells
- Even at a concentration of 50 mg/L
- Same surfactant is permitted in infant milk formulae
- At concentrations of up to 120 mg/L !!! [12]
Sucrose monoester fatty acid
- Food-grade surfactant
- Decrease in TEER [11]
- An increase in the permeability of the egg white allergen ovomucoid across Caco-2 monolayers [11]
- Perijuntional rings were partially disbanded [11]
- Major and potent surfactants used in the food industry
- Induced actin disbandment and structural separation of TJ in Caco-2 cells
- Even at a concentration of 50 mg/L
- Same surfactant is permitted in infant milk formulae
- At concentrations of up to 120 mg/L !!! [12]
Sulfur-containing amino acids
- Cystine, cysteine and methionine
- Enhance epithelial TJ permeability [12]
Sulfur-containing amino acids
- Cystine, cysteine and methionine
- Enhance epithelial TJ permeability [12]
Surfactants
- Decrease the hydrophobicity of the mucus layer
- Has also been shown to associate with increased intestinal permeability [12]
- Synthetic surfactant food additives can cause intestinal barrier dysfunction [12]
Surfactants
- Decrease the hydrophobicity of the mucus layer
- Has also been shown to associate with increased intestinal permeability [12]
- Synthetic surfactant food additives can cause intestinal barrier dysfunction [12]
Sweet pepper extract
- Found to decrease TEER in Caco-2 monolayers after a 10-min incubation period [11]
Sweet pepper extract
- Found to decrease TEER in Caco-2 monolayers after a 10-min incubation period [11]
Syndrom krátkého střeva
- Nezávisle na příčině resekce [7]
- Korelace s recentní sepsí a poškozením jater [7]
- Ileo-pouch anastomoza
- Bez ohledu na příčinu resekce [7]
Syndrom krátkého střeva
- Nezávisle na příčině resekce [7]
- Korelace s recentní sepsí a poškozením jater [7]
- Ileo-pouch anastomoza
- Bez ohledu na příčinu resekce [7]
Tacrolimus
- Induction of IP leads to more food allergies [10]
Tacrolimus
- Induction of IP leads to more food allergies [10]
TNF alfa
- Usually increase the rate of cell shedding [5]
- Prominent role in tight junction disruption [10]
- Leads to a decrease in TEER
- An increase in epithelial permeability [11]
- TEER decrease can be prevented by preincubating with
- S. thermophilus ATCC19258
- L. acidophilus ATCC4356
- Commensal Bacteroides thetaiotaomicron ATCC29184
- Signal transduction via epithelial cell surface receptor
- Reduces TNF?-induced p38 phosphorylation:
- DNA from the commensal bacteria
- Lactobacillus rhamnosus GG
- Bifidobacterium longum SP 07/3 [11]
- TNF increases leak pathway flux
- By a rapid mechanism
- Reorganization of the tight junction and perijunctional actomyosin ring
- Process that requires myosin light chain kinase (MLCK) [15]
- One of the main effectors of IBD inflammation
- May modulate the transcription of TJs proteins
- Alters permeability
- Apoptosis of enterocytes
- Increasing their rate of shedding
- Hindering the redistribution of TJs
- Seal the gaps left [16]
TNF alfa
- Usually increase the rate of cell shedding [5]
- Prominent role in tight junction disruption [10]
- Leads to a decrease in TEER
- An increase in epithelial permeability [11]
- TEER decrease can be prevented by preincubating with
- S. thermophilus ATCC19258
- L. acidophilus ATCC4356
- Commensal Bacteroides thetaiotaomicron ATCC29184
- Signal transduction via epithelial cell surface receptor
- Reduces TNF?-induced p38 phosphorylation:
- DNA from the commensal bacteria
- Lactobacillus rhamnosus GG
- Bifidobacterium longum SP 07/3 [11]
- TNF increases leak pathway flux
- By a rapid mechanism
- Reorganization of the tight junction and perijunctional actomyosin ring
- Process that requires myosin light chain kinase (MLCK) [15]
- One of the main effectors of IBD inflammation
- May modulate the transcription of TJs proteins
- Alters permeability
- Apoptosis of enterocytes
- Increasing their rate of shedding
- Hindering the redistribution of TJs
- Seal the gaps left [16]
Trans-10 isomer of conjugated linoleic acids
- Slower rate of TEER increase
- Increased paracellular flux
- Altered distribution of occludin and ZO-1 [11]
Trans-10 isomer of conjugated linoleic acids
- Slower rate of TEER increase
- Increased paracellular flux
- Altered distribution of occludin and ZO-1 [11]
Trypsin and tryptase expression and release
- Increased in colonic biopsies from IBS patients x control
- Biopsies and its supernatants from IBS patients
- Released mediators that sensitized murine sensory neurons in culture
- Prevented by a serine protease inhibitor
- Absent in neurons lacking functional protease-activated receptor–2 (PAR2)
- Caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon
- Inhibited by serine protease inhibitors
- Inhibited by PAR2 antagonist
- Absent in PAR2-deficient mice [28]
Proteases are released in IBS
- Can directly stimulate sensory neurons
- Generate hypersensitivity symptoms
- Through the activation of PAR2 [28]
PAR2 activation
- Modifies intestinal chloride secretion
- Induces signs of inflammation
- Modifies gastrointestinal motility patterns in vivo and in vitro
- Activation on visceral nociceptive functions [28]
PAR2 agonists
- Evoke an increase in intestinal barrier permeability
- Evoke long-lasting visceral hypersensitivity and hyperexcitability of enteric neurons [28]
Trypsin and tryptase expression and release
- Increased in colonic biopsies from IBS patients x control
- Biopsies and its supernatants from IBS patients
- Released mediators that sensitized murine sensory neurons in culture
- Prevented by a serine protease inhibitor
- Absent in neurons lacking functional protease-activated receptor–2 (PAR2)
- Caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon
- Inhibited by serine protease inhibitors
- Inhibited by PAR2 antagonist
- Absent in PAR2-deficient mice [28]
Proteases are released in IBS
- Can directly stimulate sensory neurons
- Generate hypersensitivity symptoms
- Through the activation of PAR2 [28]
PAR2 activation
- Modifies intestinal chloride secretion
- Induces signs of inflammation
- Modifies gastrointestinal motility patterns in vivo and in vitro
- Activation on visceral nociceptive functions [28]
PAR2 agonists
- Evoke an increase in intestinal barrier permeability
- Evoke long-lasting visceral hypersensitivity and hyperexcitability of enteric neurons [28]
Tryptophan
- In supraphysiologic levels
- Disrupts TJ in hamster small intestinal epithelia
- Perturbations in TJ (transmission electron microscopy)
- Decreased TEER
- Increased insulin flux [11]
Tryptophan
- In supraphysiologic levels
- Disrupts TJ in hamster small intestinal epithelia
- Perturbations in TJ (transmission electron microscopy)
- Decreased TEER
- Increased insulin flux [11]
Ulcerous collitis
- Down-regulation of claudin-1 and -4 and occludin
- Up-regulation of pore-forming claudin-2 [5]
- Mild permeability increases may activate immunoregulatory pathways
- That can limit colitis upon subsequent challenge / rozvinout u disponovaných jedinců [15]
Ulcerous collitis
- Down-regulation of claudin-1 and -4 and occludin
- Up-regulation of pore-forming claudin-2 [5]
- Mild permeability increases may activate immunoregulatory pathways
- That can limit colitis upon subsequent challenge / rozvinout u disponovaných jedinců [15]
Vibrio cholerae
- Secretes a variety of toxins
- Zonula occludens toxin (Zot)
- Zonulin = human homolog of the toxin
- Increase paracellular permeability [3]
- Binds specific proteinase activating receptor (PAR)2
- protein kinase C (PKC)-?-dependent polymerization of actin microfilaments
- Reversible opening of intercellular TJ [13]
- Bindins to an apical membrane receptor (zonulin) on the enterocyte
- Activation of an intracellular pathway
- Actomyosin contraction
- Increased paracellular permeability
- Where permeability is increased:
- Upregulation of zonulin secretion from a lamina propria source into the lumen
- With inappropriate activation of this pathway
- Result is increased paracellular permeability [3]
- Modulate TJ [11]
Vibrio cholerae
- Secretes a variety of toxins
- Zonula occludens toxin (Zot)
- Zonulin = human homolog of the toxin
- Increase paracellular permeability [3]
- Binds specific proteinase activating receptor (PAR)2
- protein kinase C (PKC)-?-dependent polymerization of actin microfilaments
- Reversible opening of intercellular TJ [13]
- Bindins to an apical membrane receptor (zonulin) on the enterocyte
- Activation of an intracellular pathway
- Actomyosin contraction
- Increased paracellular permeability
- Where permeability is increased:
- Upregulation of zonulin secretion from a lamina propria source into the lumen
- With inappropriate activation of this pathway
- Result is increased paracellular permeability [3]
- Modulate TJ [11]
Yersinias
Yersinias
Subclinical inflammation
- Patients with increased permeability
- Likely to have evidence of subclinical inflammation
- Assessed by calprotectin excretion [4]
- Inflammations and autoimmunity with elevated:
- IFN gamma, IL-2, IL-13, TNF alpha, CRP, IL-6 …
- Including obesity with its low intensity inflammation !!!
Subclinical inflammation
- Patients with increased permeability
- Likely to have evidence of subclinical inflammation
- Assessed by calprotectin excretion [4]
- Inflammations and autoimmunity with elevated:
- IFN gamma, IL-2, IL-13, TNF alpha, CRP, IL-6 …
- Including obesity with its low intensity inflammation !!!
Zonulin = Pre-Haptoglobin 2
- Precursor for HP2 [13]
- Zonulin is overexpressed
- In tissues and sera of subjects affected by autoimmune diseases [13]
- Zonulin-positive and zonulin-negative T1D and CD [13]
- TJ regulation by zonulin is responsible for
- Movement of fluid
- Macromolecules
- Leukocytes between the bloodstream and the intestinal lumen [13]
- Protection against microorganism colonization of the proximal intestine
- Innate immunity [13]
- Recombinant pre-HP2 alters intestinal permeability [13]
- Induced a time- and dose-dependent reduction in TEER when added to murine small intestinal mucosa [13]
- Increase in both gastroduodenal and small intestinal permeability [13]
- Zonulin cleaved in its ?- and ß-subunits lost the permeating activity [13]
- Activate EGF receptor (EGFR) [13]
- G protein-coupled receptors (GPCR) transactivate EGFR
- PAR2 [13]
- Effect on TEER was prevented by the EGFR tyrosine kinase inhibitor AG-1478 [13]
- Failed to reduce TEER in small intestinal segments from PAR2-/- mice [13]
Mature human HPs
- Bind Hb to form stable HP-Hb complexes
- Preventing Hb-induced oxidative tissue damage [13]
- Heterodimeric plasma glycoproteins
- Z alfa a beta-polypeptide chains
- Covalently associated by disulfide bonds
- Only the beta-chain is glycosylated [13]
- Alfa chain exists in two forms
- Alfa 1 and alfa 2 = zonulin
- Three human HP phenotypes:
- HP1–1 homozygote = 0 zonulinu
- Only 7% of CD patients do not possess the zonulin gene [13]
- HP2–1 heterozygote = 1 zonulin
- Associated with a significant risk of CD [13]
- HP2–2 homozygote = 2 x zonulin [13]
- Less frequent in CD patients
- Increased risk for severe malabsorption on CD and higher mortality [13]
- ELISA anti-Zot antibodies
- Recognize both ?1- and ?2-chains
- Under nondenaturing conditions they immunoreacted only with HP2–2 phenotype [13]
- Hypothesize that the activity of Cr-like protein modulates the zonulin pool [13]
- Clearance of the HP-Hb complex
- Can be mediated by the monocyte/macrophage scavenger receptor CD163 [13]
Stimuli That Cause Zonulin Release in the Gut
- Intestinal exposure to bacteria
- Gluten [13]
- Followed by an increase in intestinal permeability
- Disengagement of the protein ZO-1 from the tight junctional complex [13]
Zonulin = Pre-Haptoglobin 2
- Precursor for HP2 [13]
- Zonulin is overexpressed
- In tissues and sera of subjects affected by autoimmune diseases [13]
- Zonulin-positive and zonulin-negative T1D and CD [13]
- TJ regulation by zonulin is responsible for
- Movement of fluid
- Macromolecules
- Leukocytes between the bloodstream and the intestinal lumen [13]
- Protection against microorganism colonization of the proximal intestine
- Innate immunity [13]
- Recombinant pre-HP2 alters intestinal permeability [13]
- Induced a time- and dose-dependent reduction in TEER when added to murine small intestinal mucosa [13]
- Increase in both gastroduodenal and small intestinal permeability [13]
- Zonulin cleaved in its ?- and ß-subunits lost the permeating activity [13]
- Activate EGF receptor (EGFR) [13]
- G protein-coupled receptors (GPCR) transactivate EGFR
- PAR2 [13]
- Effect on TEER was prevented by the EGFR tyrosine kinase inhibitor AG-1478 [13]
- Failed to reduce TEER in small intestinal segments from PAR2-/- mice [13]
Mature human HPs
- Bind Hb to form stable HP-Hb complexes
- Preventing Hb-induced oxidative tissue damage [13]
- Heterodimeric plasma glycoproteins
- Z alfa a beta-polypeptide chains
- Covalently associated by disulfide bonds
- Only the beta-chain is glycosylated [13]
- Alfa chain exists in two forms
- Alfa 1 and alfa 2 = zonulin
- Three human HP phenotypes:
- HP1–1 homozygote = 0 zonulinu
- Only 7% of CD patients do not possess the zonulin gene [13]
- HP2–1 heterozygote = 1 zonulin
- Associated with a significant risk of CD [13]
- HP2–2 homozygote = 2 x zonulin [13]
- Less frequent in CD patients
- Increased risk for severe malabsorption on CD and higher mortality [13]
- ELISA anti-Zot antibodies
- Recognize both ?1- and ?2-chains
- Under nondenaturing conditions they immunoreacted only with HP2–2 phenotype [13]
- Hypothesize that the activity of Cr-like protein modulates the zonulin pool [13]
- Clearance of the HP-Hb complex
- Can be mediated by the monocyte/macrophage scavenger receptor CD163 [13]
Stimuli That Cause Zonulin Release in the Gut
- Intestinal exposure to bacteria
- Gluten [13]
- Followed by an increase in intestinal permeability
- Disengagement of the protein ZO-1 from the tight junctional complex [13]
Ostatní nemoci související se zvýšenou SP
- Inflammatory response syndrome
- Allergies, food allergies, hypersensitivity [10]
- Withdrawal of the food allergen for six months was not accompanied by IP improvements [10]
- Asthma
- Cca 40% of asthmatic patients have an increased intestinal permeability [13]
- Autism
- Chronic urticaria [10]
- Atopic dermatitis [10]
- Ankylosing spondylitis [10]
- Campylobacter infection increases IP [10]
- IgA nephropathy [11]
- Nonalcoholic steatohepatitis [11]
- Multiple sclerosis [11]
- 25% of MS patients studied had an increased intestinal permeability [13]
- Increased number of peripheral B cells exhibiting CD45RO
- Marker of antigen exposure [13]
- Juvenile onset arthritis [13, 14]
- Psoriatic arthritis
- Primary biliary cirrhosis [12]
- Glioma
- Increase in zonulin expression in gliomas [13]
- Malignancy of human brain cancers correlated with:
- C-kit - cancer and degeneration marker of gliomas [13]
- Increase of zonulin expression [13]
- Correlated with the degradation of the blood-brain barrier - severity of the neoplastic [13]
- Chronic fatigue syndrome [14]
- Chronic heart failure [14]
- Psychological conditions [14]
Ostatní nemoci související se zvýšenou SP
- Inflammatory response syndrome
- Allergies, food allergies, hypersensitivity [10]
- Withdrawal of the food allergen for six months was not accompanied by IP improvements [10]
- Asthma
- Cca 40% of asthmatic patients have an increased intestinal permeability [13]
- Autism
- Chronic urticaria [10]
- Atopic dermatitis [10]
- Ankylosing spondylitis [10]
- Campylobacter infection increases IP [10]
- IgA nephropathy [11]
- Nonalcoholic steatohepatitis [11]
- Multiple sclerosis [11]
- 25% of MS patients studied had an increased intestinal permeability [13]
- Increased number of peripheral B cells exhibiting CD45RO
- Marker of antigen exposure [13]
- Juvenile onset arthritis [13, 14]
- Psoriatic arthritis
- Primary biliary cirrhosis [12]
- Glioma
- Increase in zonulin expression in gliomas [13]
- Malignancy of human brain cancers correlated with:
- C-kit - cancer and degeneration marker of gliomas [13]
- Increase of zonulin expression [13]
- Correlated with the degradation of the blood-brain barrier - severity of the neoplastic [13]
- Chronic fatigue syndrome [14]
- Chronic heart failure [14]
- Psychological conditions [14]
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