Regulation of Intestinal Barrier Function by Microbial Metabolites

In the paper

“Enterocytes connect with each other in a continuous epithelial cell layer via adhesive junctional proteins that make up tight junction (TJ) proteins, adherens junction (AJ) proteins, gap junction proteins, and desmosomes (Table 2).31,32”

What the sources say

• Not checked yetcites [31] Niessen, 2007, Tight junctions/adherens junctions: basic structure and function, J Invest Dermatol source
• Not checked yetcites [32] Groschwitz, 2009, Intestinal barrier function: molecular regulation and disease pathogenesis, J Allergy Clin Immunol source

In the paper

“Increased gut barrier permeability occurs through dysregulation of epithelial apoptosis/enterocyte death, mucus degradation, and increased paracellular permeability due to disruption of TJs.”

In the paper

“TNF-α induced loss of the epithelial integrity due to apoptosis accounted for about 56% of the damage and the rest was by disruption of TJs in nonapoptotic areas.57”

What the sources say

• Not checked yetcites [57] Gitter, 2000, Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis, FASEB J source

In the paper

“Humans and microbes have coevolved over millions of years, thereby contributing to the interdependency of host and microbiota physiological activities.1”

What the sources say

• Not checked yetcites [1] Li, 2008, Symbiotic gut microbes modulate human metabolic phenotypes, Proc Natl Acad Sci U S A source

In the paper

“For example, Gitter et al57 showed that tumor necrosis factor alpha (TNF-α) disrupts the gut barrier not only by degradation in TJs, but also through the induction of epithelial apoptosis.”

What the sources say

• Not checked yetcites [57] Gitter, 2000, Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis, FASEB J source

In the paper

“TJ proteins consist of over 50 proteins that are crucial for maintaining cell-to-cell adhesion and gut barrier health.36”

What the sources say

• Not checked yetcites [36] Chiba, 2008, Transmembrane proteins of tight junctions, Biochim Biophys Acta source

In the paper

“The leak pathway is believed to be regulated by myosin light-chain kinase (MLCK), where constitutively active MLCK is sufficient to increase the leak pathway–dependent permeability both in vitro and in vivo.52,53”

What the sources say

• Not checked yetcites [52] Shen, 2006, Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure, J Cell Sci source
• Not checked yetcites [53] Su, 2009, Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis, Gastroenterology source

In the paper

“The gut barrier is composed of 3 main interlinked/interdependent layers that provides a physical barrier against bacterial intrusion from the gut lumen.”

In the paper

“The functional or physical disruption of TJ, AJ, and gap junction proteins and desmosomes leads to increased gut permeability causing dysregulated translocation/transportation of inflammatory mediators, which potentially manifests as chronic gut inflammation.”

In the paper

“The flux that occurs due to cell death (global barrier loss) is classified as “unrestricted pathway,” in which there is no size limit of molecules or antigens that can cross the membrane.48”

What the sources say

• Not checked yetcites [48] Zuo, 2020, Tight junctions as targets and effectors of mucosal immune homeostasis, Cell Mol Gastroenterol Hepatol source

In the paper

“It was demonstrated by the Stockinger group that deletion of AhR in IECs led to a defective barrier and uncontrolled proliferation of intestinal stem cells, leading to increased tumors in an azoxymethane-DSS–induced colon tumorigenesis model.100”

What the sources say

• Not checked yetcites [100] Metidji, 2019, The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity, Immunity source

In the paper

“Supplementation of dietary AhR ligands (like I3C) guarded the intestinal stem cell niche and maintained intestinal barrier function and decreased tumor burden in the azoxymethane-DSS–induced colon tumorigenesis model.100”

What the sources say

• Not checked yetcites [100] Metidji, 2019, The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity, Immunity source

In the paper

“FMT has resulted in enhanced metabolic functions of gut microbiota associated with indole alkaloid biosynthesis such as indole-3-acetic acid that in turn enhances gut barrier homeostasis.91”

What the sources say

• Not checked yetcites [91] Geng, 2018, Faecal microbiota transplantation reduces susceptibility to epithelial injury and modulates tryptophan metabolism of the microbial community in a piglet model, J Crohns Colitis

In the paper

“Further, they have been shown to significantly influence the maintenance of gut barrier integrity itself and intestinal homeostasis.73,74”

What the sources say

• Not checked yetcites [73] Alam, 2018, Role of gut microbiota in intestinal wound healing and barrier function, Tissue Barriers source
• Not checked yetcites [74] Prochazkova, 2019, Microbiota, microbial metabolites, and barrier function in a patient with anorexia nervosa after fecal microbiota transplantation, Microorganisms source

In the paper

“The host-microbiota relationship has been defined as the synergistic effect of microbial metabolites on host immunity, health and disease, energy metabolism, and cellular communication.59, 60, 61, 62, 63,64”

What the sources say

• Not checked yetcites [59] Jandhyala, 2015, Role of the normal gut microbiota, World J Gastroenterol source
• Not checked yetcites [60] Thursby, 2017, Introduction to the human gut microbiota, Biochem J source
• Not checked yetcites [61] Li, 2018, Effects of metabolites derived from gut microbiota and hosts on pathogens, Front Cell Infect Microbiol source
• Not checked yetcites [62] Araki, 1995, Enhancement of resistance to bacterial infection in mice by vitamin B2, J Vet Med Sci source
• Not checked yetcites [63] Donia, 2015, Human microbiota. Small molecules from the human microbiota, Science source
• Not checked yetcites [64] Artis, 2008, Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut, Nat Rev Immunol source

In the paper

“Activation of AhR by tryptophan metabolites promotes immune cell maturation and decreased pathogen colonization.89”

What the sources say

• Not checked yetcites [89] Zelante, 2013, Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22, Immunity source

In the paper

“Levels of TJ proteins in AhR–/– mice are also significantly reduced compared with wild type mice leading to increased gut leakiness.22”

What the sources say

• Not checked yetcites [22] Singh, 2019, Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway, Nat Commun source

In the paper

“Moreover, butyrate treatment resulted in downregulation of IL-1β levels, suggesting it may be beneficial for protection against inflammation-promoted barrier disruption.87”

What the sources say

• Not checked yetcites [87] Diao, 2019, Gastric infusion of short-chain fatty acids can improve intestinal barrier function in weaned piglets, Genes Nutr source

In the paper

“Similarly, butyrate improved barrier function at lower doses, but reduced barrier function at higher doses in Caco-2 cells.80”

What the sources say

• Not checked yetcites [80] Peng, 2007, Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier, Pediatr Res source

In the paper

“However, at higher concentrations (50–100 mM), it showed no beneficial effects on MUC2 expression patterns,79 likely due to the induction of apoptosis at higher doses.”

What the sources say

• Not checked yetcites [79] Nielsen, 2018, Effect of butyrate and fermentation products on epithelial integrity in a mucus-secreting human colon cell line, Journal of Functional Foods source

In the paper

“Microbial metabolites produced in the gut directly interact with IECs and immune cells and impact host health.61,62”

What the sources say

• Not checked yetcites [61] Li, 2018, Effects of metabolites derived from gut microbiota and hosts on pathogens, Front Cell Infect Microbiol source
• Not checked yetcites [62] Araki, 1995, Enhancement of resistance to bacterial infection in mice by vitamin B2, J Vet Med Sci source

In the paper

“AhR activation by FICZ was therapeutic in the dextran sodium sulfate (DSS)–induced mouse colitis model in which FICZ treatment upregulated TJ protein expression in inflamed mouse colons.92,93”

What the sources say

• Not checked yetcites [92] Yu, 2018, Aryl hydrocarbon receptor activation modulates intestinal epithelial barrier function by maintaining tight junction integrity, Int J Biol Sci source
• Not checked yetcites [93] Teng, 2018, Plant-derived exosomal MicroRNAs shape the gut microbiota, Cell Host Microbe source

In the paper

“Thus far, it is estimated that ∼50,000 microbial metabolites are produced by microbes in the human gut.”

In the paper

“These primary bile acids, cholic acid and chenodeoxycholic acid (CDCA), are transported into the gut through the enterohepatic circulation system and are further metabolized by gut microbiota by dehydroxylation, dehydrogenation, and epimerization to generate secondary bile acids reviewed previously.102”

What the sources say

• Not checked yetcites [102] Dawson, 2015, Intestinal transport and metabolism of bile acids, J Lipid Res source

In the paper

“In summary, bile acids have been shown to be a double-edged sword and an appropriate balance (ratio) of different bile acids is required to mediate gut barrier protective activity.”

In the paper

“Polyamines exhibit numerous beneficial effects including increased longevity, recovery of injured mucosa, as well as favorable effects on cognitive function.122, 123, 124”

What the sources say

• Not checked yetcites [122] Tofalo, 2019, Polyamines and gut microbiota, Front Nutr source
• Not checked yetcites [123] Timmons, 2012, Polyamines and gut mucosal homeostasis, J Gastrointest Dig Syst
• Not checked yetcites [124] Matsumoto, 2011, Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production, PLoS One source

In the paper

“Treatment with the trans-10 CLA isomer caused a redistribution of ZO-1 and OCLN and increased paracellular permeability in Caco-2 colon epithelial cells.119”

What the sources say

• Not checked yetcites [119] Roche, 2001, Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells, Gut source

In the paper

“Additionally, treatment with CLNA1 and CLNA2 significantly reduced inflammatory mediators (TNF-α, IL-1β, and IL-6) while upregulating the expression of the colonic anti-inflammatory cytokine IL-10 and nuclear receptor peroxisome-activated receptor-γ.”

In the paper

“It was showed that mice exposed to broad-spectrum antibiotics such as ampicillin, clindamycin and streptomycin resulted in reduced gut bacterial diversity and richness and impacted gut barrier integrity.112”

What the sources say

• Not checked yetcites [112] Liu, 2020, Naturally occurring TPE-CA maintains gut microbiota and bile acids homeostasis via FXR signaling modulation of the liver-gut axis, Front Pharmacol source

In the paper

“Ren et al reported that the probiotic L. plantarum ZS2058 produced isomers of conjugated fatty acids, α-linolenic acid (conjugated linolenic acid (CLNA) 1 and CLNA2) mitigated DSS-induced colitis by enhancing gut barrier function through upregulation of ZO-1, OCLN, CLDN-3, and E-cadherin 1 in colonic tissues.”

In the paper

“TPE-CA treatment induced the expression of TJ proteins such as ZO-1 and OCLN-associated proteins in these mice and improved the barrier integrity.112”

What the sources say

• Not checked yetcites [112] Liu, 2020, Naturally occurring TPE-CA maintains gut microbiota and bile acids homeostasis via FXR signaling modulation of the liver-gut axis, Front Pharmacol source

In the paper

“The colons of GP-BAR1–/– mice exhibit altered subcellular distribution of ZO-1, leading to increased gut permeability.”

In the paper

“In contrast, UDCA did not alter gut permeability but blocked the DCA-induced permeability in murine jejunal and colonic preparations.”

In the paper

“Further, treatment with dietary flavanones and their glycosyl derivatives such as total phenolic extracts of Citrus aurantium L (TPE-CA) restored bacterial diversity and improved gut barrier integrity and homeostasis of bile acids.”

In the paper

“Treatment with CDCA decreased the expression of Ocln and TEER values leading to increased permeability as well as an increase in the inflammatory cytokine IL-8.”

In the paper

“The effects of these bile acids were mediated by the Src family kinases and was abolished by EGF treatment.110”

What the sources say

• Not checked yetcites [110] Raimondi, 2008, Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation, Am J Physiol Gastrointest Liver Physiol source

In the paper

“Using a Caco-2 cell model, Raimondi et al110 showed that DCA and CDCA, but not UDCA, treatment decreased TEER and increased permeability.”

What the sources say

• Not checked yetcites [110] Raimondi, 2008, Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation, Am J Physiol Gastrointest Liver Physiol source

In the paper

“Fexaramine, an intestine-restricted FXR agonist, restored intestinal FXR activity and gut barrier integrity in an ALD model.”

In the paper

“These treatments also rebalanced the intestinal microbial composition in the colons of DSS-treated mice, including increasing the α-diversity.121”

What the sources say

• Not checked yetcites [121] Ren, 2020, c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 ameliorate dextran sodium sulfate-induced colitis in mice, J Agric Food Chem source

In the paper

“Importantly, CLA treatment reduced the prevalence of Bacteroides and increased Bifidobacterium and Odoribacter in this model.”

What the sources say

• Not checked yetcites [120] Chen, 2019, Orally administered CLA ameliorates DSS-induced colitis in mice via intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokine and gut microbiota modulation, J Agric Food Chem source

In the paper

“Some bile acid metabolites can both improve as well as exert negative effects on gut barrier TJ function.104”

What the sources say

• Not checked yetcites [104] Sarathy, 2017, The Yin and Yang of bile acid action on tight junctions in a model colonic epithelium, Physiol Rep source

In the paper

“Although LCA by itself neither altered barrier function nor increased IL-8 production, LCA attenuated CDCA-induced barrier permeability and IL-8 production.”

In the paper

“Among urolithins, urolithin A (UroA) displays potent anti-inflammatory, antioxidative, and antiaging properties.130,133, 134, 135”

What the sources say

• Not checked yetcites [130] Espin, 2013, Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far, Evid Based Complement Alternat Med source
• Not checked yetcites [133] Tomas-Barberan, 2017, Urolithins, the rescue of 'old' metabolites to understand a 'new' concept: metabotypes as a nexus between phenolic metabolism, microbiota dysbiosis and host health status, Mol Nutr Food Res source
• Not checked yetcites [134] Ryu, 2016, Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents, Nat Med source

In the paper

“A human phase I clinical trial showed that a polyphenol-rich diet modulates gut microbiota and reduces intestinal permeability, including decreased transport of pathogenic microbes into the bloodstream.150”

What the sources say

• Not checked yetcites [150] Guglielmetti, 2020, Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial, BMC Geriatr source

In the paper

“In summary, numerous microbial metabolites discussed previously shown to exhibit direct impact on gut epithelium and play an important role in regulating gut barrier function thereby mucosal immunity and vice versa.”

In the paper

“Johnson et al151 reported that dietary polyphenols such as isoflavones and lignans and corresponding microbial metabolites protected the gut epithelium by reducing permeability and inhibited LPS-induced inflammation.”

What the sources say

• Not checked yetcites [151] Johnson, 2019, Polyphenol microbial metabolites exhibit gut and blood(-)brain barrier permeability and protect murine microglia against LPS-induced inflammation, Metabolites source

In the paper

“Two factors are critical for the generation of UroA in humans (1) presence of UroA producing bacteria and (2) consumption of EA/ET-containing foods (eg, pomegranate, berries, walnuts).”

In the paper

“Bacterial polyamines include spermidine, homospermidine, norspermidine, putrescine, cadaverine, and 1,3-diaminopropane with putrescine and spermidine.125”

What the sources say

• Not checked yetcites [125] Michael, 2016, Biosynthesis of polyamines and polyamine-containing molecules, Biochem J source

In the paper

“It was shown that depletion of cellular polyamines by α-difluoromethylornithine reduced intracellular free Ca2+ concentrations in normal IECs (IEC-6 cell line),127 which leads to decreased expression of E-cadherin and increased paracellular permeability.”

What the sources say

• Not checked yetcites [127] Guo, 2003, Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines, Am J Physiol Cell Physiol source

In the paper

“However, exogenous supplementation of the spermidine reversed the effects of α-difluoromethylornithine on intracellular Ca2+ and E-cadherin expression and restored paracellular permeability to near normal levels.128”

What the sources say

• Not checked yetcites [128] Guo, 2005, Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells, Am J Physiol Gastrointest Liver Physiol source

In the paper

“Importantly, treatment with UroA mitigated DSS- or TNBS-induced colitis in mice through enhancing gut barrier function and blocking the production of inflammatory cytokines.22”

What the sources say

• Not checked yetcites [22] Singh, 2019, Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway, Nat Commun source

In the paper

“NOD1 and NOD2 knockout mice exhibit increased paracellular permeability and are reported to be more susceptible to DSS colitis mediated intestinal injury.177”

What the sources say

• Not checked yetcites [177] Natividad, 2012, Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1–/–; Nod2–/– mice, Inflamm Bowel Dis source

In the paper

“These receptors, which play crucial roles in host-microbiota interactions, are expressed at various levels in different cell types such as IECs, innate lymphoid cells, macrophages, T cells, and dendritic cells.184”

What the sources say

• Not checked yetcites [184] Furusawa, 2013, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, Nature source

In the paper

“Although blocking TLR4 with antibodies limited acute inflammation in the DSS model, subsequent tissue repair was hampered, suggesting an important role for TLR4 in the resolution of inflammation and restoration of tissue integrity.162”

What the sources say

• Not checked yetcites [162] Ungaro, 2009, A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis, Am J Physiol Gastrointest Liver Physiol source

In the paper

“Flagellin, a structural component of bacterial flagellum, is exerted activities through TLR5 and has been shown to play an essential and nonredundant role in protecting the gut from enteric microbes.164”

What the sources say

• Not checked yetcites [164] Steiner, 2007, How flagellin and toll-like receptor 5 contribute to enteric infection, Infect Immun source

In the paper

“Couturier-Millard et al178 reported that NOD2 deficiency leads to microbial dysbiosis leading to increased risk of colitis.”

What the sources say

• Not checked yetcites [178] Couturier-Maillard, 2013, NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer, J Clin Invest

In the paper

“TLR9–/– mice are more susceptible to DSS-induced colitis compared with wild types mice, suggesting that activation of TLR9 is important for protection against intestinal damage through induction of vascular EGF and intestinal progenitor cell differentiation as well as being critical for wound repair mechanisms.171”

What the sources say

• Not checked yetcites [171] Rose, 2012, TLR9 is important for protection against intestinal damage and for intestinal repair, Sci Rep source

In the paper

“Numerous studies including ours showed that LPS disrupts junctional protein complexes and increases inflammatory cytokines leading to increased gut permeability.”

In the paper

“Furthermore, muramyl dipeptide or peptidoglycan mediated activation of NOD2 is reported to negatively regulate TLR signaling and provide protection of wildtype mice against colitis.175,176”

What the sources say

• Not checked yetcites [175] Watanabe, 2008, Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis, J Clin Invest
• Not checked yetcites [176] Macho Fernandez, 2011, Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide, Gut source

In the paper

“IECs express TLR2 that recognizes bacterial lipopeptides, lipoteichoic acid and yeast zymosan, and forms heterodimers with TLR1 or TLR 6.157”

What the sources say

• Not checked yetcites [157] Creagh, 2006, TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity, Trends Immunol source

In the paper

“It was demonstrated in numerous reports from Dr Gewirtz’s group that expression and activation of TLR5 on IECs regulates the composition and localization of microbiota and prevents disease associated intestinal inflammation.165, 166, 167, 168”

What the sources say

• Not checked yetcites [165] Chassaing, 2014, Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice, Gastroenterology source
• Not checked yetcites [166] Vijay-Kumar, 2007, Deletion of TLR5 results in spontaneous colitis in mice, J Clin Invest
• Not checked yetcites [167] Leifer, 2014, Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome's potential to cause inflammation, Immunol Lett source

In the paper

“Functional immune responses often modulate gut barrier integrity; hence, the fine tuning of gut microbiota to evoke necessary immune responses to alter intestinal barrier function is critical.”

In the paper

“It was reported that Nod1–/– mice have increased levels of intestinal permeability and inflammation in the murine DSS-induced colitis model compared with wild type mice,174 suggesting an important role in intestinal barrier function.”

What the sources say

• Not checked yetcites [174] Chen, 2008, The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis, Cancer Res source

In the paper

“Ligand-induced TLR2 activation leads to the specific activation of protein kinase C α (PKC-α) and PKC-δ and is responsible for increased TEER as well as increased apical tightening and sealing of the TJs.”

In the paper

“PKC phosphorylation by TLR2 activation leads to stabilization of ZO-1, which is a target of PKC.”

In the paper

“The absence of NOD protein–mediated microbial sensing leads to a loss of gut barrier homeostasis and leads to increased susceptibility to gut inflammatory diseases.176”

What the sources say

• Not checked yetcites [176] Macho Fernandez, 2011, Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide, Gut source

In the paper

“NLRs proteins are also responsible for maintaining gut barrier integrity by sensing the presence of commensal microbiota and the regulation of intestinal inflammation.172,173”

What the sources say

• Not checked yetcites [172] Parlato, 2014, NOD-like receptors in intestinal homeostasis and epithelial tissue repair, Int J Mol Sci source
• Not checked yetcites [173] Yeretssian, 2012, Effector functions of NLRs in the intestine: innate sensing, cell death, and disease, Immunol Res source

In the paper

“Activation of TLR5 by flagellin in ileal tissues of SAMP1/YitFc (SAMP) mice (a spontaneous model of Crohn's disease–like ileitis) led to decreased epithelial barrier resistance and altered expression of the TJ proteins CLDN-3, OCLN, and ZO-1.169”

What the sources say

• Not checked yetcites [169] Lopetuso, 2017, Epithelial-specific Toll-like receptor (TLR)5 activation mediates barrier dysfunction in experimental ileitis, Inflamm Bowel Dis source

In the paper

“Another therapeutic approach includes blocking Th1 responses or using neutralizing antibodies such as infliximab (anti-TNF) antibody.189,190”

What the sources say

• Not checked yetcites [189] Powrie, 1994, Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells, Immunity source
• Not checked yetcites [190] Noth, 2012, Anti-TNF-alpha antibodies improve intestinal barrier function in Crohn's disease, J Crohns Colitis source

In the paper

“For example, sex hormones such as estrogen and progesterone induced expression of TJ proteins and inhibited gut permeability in inflammatory organoid models from IBD patients and 2D cell line models.200”

What the sources say

• Not checked yetcites [200] van der Giessen, 2019, A direct effect of sex hormones on epithelial barrier function in inflammatory bowel disease models, Cells source

In the paper

“Implantation of 17 pre-selected clostridial bacterial strains that are capable of enhancing Treg cell abundance and inducing anti-inflammatory mediators, IL-10 and inducible T-cell co-stimulator, into GF mice attenuated TNBS-induced colitis and enhanced gut barrier function.192”

What the sources say

• Not checked yetcites [192] Atarashi, 2013, Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota, Nature source

In the paper

“Zhou et al201 reported that progesterone upregulated OCLN expression in the gut and inhibited NF-κB activation to maintain gut barrier homeostasis.”

What the sources say

• Not checked yetcites [201] Zhou, 2019, Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells, Sci Rep source

In the paper

“Additionally, UroA and UAS03 also blocked unwarranted inflammation and mitigated colitis in pre-clinical models.22”

What the sources say

• Not checked yetcites [22] Singh, 2019, Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway, Nat Commun source

In the paper

“Last, but definitely not the least, dietary habits and a healthy lifestyle are of the foremost importance in maintaining healthy intestinal barrier functions.207”

What the sources say

• Not checked yetcites [207] Camilleri, 2019, Leaky gut: mechanisms, measurement and clinical implications in humans, Gut source

In the paper

“Further, they demonstrated that treatment with divertin corrected increased intestinal permeability in IL-10–/– mice (spontaneous colitis model) without significant systemic, mucosal, or epithelial toxicity.191”

What the sources say

• Not checked yetcites [191] Graham, 2019, Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis, Nat Med source

In the paper

“Conventional treatment strategies include the use of immunosuppressants such as azathioprine and mesalamine that are used in the clinic to treat ulcerative colitis and Crohn's disease.188”

What the sources say

• Not checked yetcites [188] Khare, 2019, Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation, Sci Rep source

In the paper

“FMT was reported to decrease antibiotic, chemotherapy, and injury-induced gut permeability and increased the prevalence of specific microbiota strains exhibiting anti-inflammatory properties.195,196”

What the sources say

• Not checked yetcites [195] Le Bastard, 2018, Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice, Sci Rep source
• Not checked yetcites [196] Schmidt, 2020, Fecal transplant prevents gut dysbiosis and anxiety-like behaviour after spinal cord injury in rats, PLoS One source

In the paper

“Though beneficial activities of microbial metabolites in regulating gut barrier function have been shown in animal models, thus far, no microbial metabolites or their analogues are in clinical use.”

In the paper

“Furthermore, probiotic strains such as L. plantarum also elevate the levels of host defense peptides such as pBD2, PG1-5 and pBD2 and improve gut barrier function.83”

What the sources say

• Not checked yetcites [83] Feng, 2018, Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy, Cell Physiol Biochem source

In the paper

“Oxyberberine, another microbial metabolite derived from berberine ameliorated gut barrier dysfunction via inhibition of the TLR4, MyD88, and NF-κB signaling pathways197 and downregulated inflammatory cytokines such as TNFα, IL-6, and IL-1β.”

What the sources say

• Not checked yetcites [197] Li, 2020, Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-kappaB pathway, Pharmacol Res source

In the paper

“Dietary cellulose supplements also can ameliorate LPS-mediated intestinal barrier damage and protect against gut epithelial apoptosis.205”

What the sources say

• Not checked yetcites [205] Di Caro, 2019, Effect of dietary cellulose supplementation on gut barrier function and apoptosis in a murine model of endotoxemia, PLoS One source

In the paper

“Dietary component such as curcumin supplementation reduced high fat diet induced hepatic steatosis by modulating the gut-liver axis and by enhancing ZO-1 and OCLN expression in the intestines.203”

What the sources say

• Not checked yetcites [203] Yang, 2019, Ellagic acid and its microbial metabolite urolithin a alleviate diet-induced insulin resistance in mice (OR24-03-19), Curr Dev Nutr source

In the paper

“Moreover, increasing recognition of the association between gut microbes, gut barrier dysfunction, and intestinal diseases highlights the importance of understanding microbial metabolite production and function.”

In the paper

“The influence of gut microbiota on intestinal barrier permeability and subsequent host cellular homeostasis is indisputable.”

In the paper

“Emerging knowledge of host-microbiota interactions allows for the development of new therapeutic strategies to restore a healthy gut ecosystem and prevent a variety of intestinal diseases.”

In the paper

“Furthermore, a deeper understanding of intestinal microbiota dynamics with respect to gut barrier function provides translational opportunities for therapeutic discovery, including drug design, microbe transplantation, and a clearer perspective of host pathophysiology.”