Dietary organic acids ameliorate high stocking density stress-induced intestinal inflammation through the restoration of intestinal microbiota in broilers

Background:High stocking density(HSD)stress has detrimental effects on growth performance,intestinal barrier function,and intestinal microbiota in intensive animal production.Organic acids(OA)are widely used as feed addi-tives for their ability to improve growth performance and intestinal health in poultry.However,whether dietary OA can ameliorate HSD stress-induced impaired intestinal barrier in broilers remains elusive.In this study,a total of 528 one-day-old male Arbor Acres broilers were randomly allocated into 3 treatments with 12 replicates per treatment including 10 birds for normal stocking density and 17 birds for HSD.The dietary treatments were as follows:1)Normal stocking density+basal diet;2)HSD+basal diets;3)HSD+OA.Results:HSD stress can induce increased levels of serum corticosterone,lipopolysaccharides,interleukin-1β,tumor necrosis factor-α,and down-regulated mRNA expression of ZO-1,resulting in compromised growth performance of broilers(P<0.05).Dietary OA could significantly reduce levels of serum corticosterone,lipopolysaccharides,interleukin-1β,and tumor necrosis factor-α,which were accompanied by up-regulated interleukin-10,mRNA expres-sion of ZO-1,and growth performance(P<0.05).Moreover,OA could down-regulate the mRNA expression of TLR4 and MyD88 to inhibit the NF-κB signaling pathway(P<0.05).Additionally,HSD stress significantly decreased the abundance of Bacteroidetes and disturbed the balance of microbial ecosystems,whereas OA significantly increased the abundance of Bacteroidetes and restored the disordered gut microbiota by reducing competitive and exploita-tive interactions in microbial communities(P<0.05).Meanwhile,OA significantly increased the content of acetic and butyric acids,which showed significant correlations with intestinal inflammation indicators(P<0.05).Conclusions:Dietary OA ameliorated intestinal inflammation and growth performance of broilers through restor-ing the disordered gut microbial compositions and interactions induced by HSD and elevating short-chain fatty acid production to inhibit the TLR4/NF-κB signaling pathway.These findings demonstrated the critical role of intestinal microbiota in mediating the HSD-induced inflammatory responses,contributing to exploring nutritional strategies to alleviate HSD-induced stress in animals.

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to protect intestinal health,it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line(IPEC-1)infected with enterotoxigenic Escherichia coli(ETEC)K88.This research was conducted to explore whether plant polyphenols including protocatechuic acid(PCA)and quercetin(Que),attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways.Methods:IPEC-1 cells were treated with PCA(40μmol/L)or Que(10μmol/L)in the presence or absence of ETEC K88.Results:PCA and Que decreased ETEC K88 adhesion and endotoxin level(P<0.05)in cell supernatant.PCA and Que increased cell number(P<0.001)and decreased lactate dehydrogenases(LDH)activity(P<0.05)in cell supernatant after ETEC infection.PCA and Que improved transepithelial electrical resistance(TEER)(P<0.001)and reduced fluorescein isothiocyanate-labeled dextran(FD4)flux(P<0.001),and enhanced membrane protein abundance of occludin,claudin-1 and ZO-1(P<0.05),and rescued distribution of these tight junction proteins(P<0.05)after ETEC infection.PCA and Que also declined cell necrosis ratio(P<0.05).PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8(P<0.001),and down-regulated gene expression of toll-like receptors 4(TLR4)and its downstream signals(P<0.001)after ETEC infection.PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1(t-RIP1),phosphorylated-RIP1(p-RIP1),p-RIP1/t-RIP1,t-RIP3,p-RIP3,mixed lineage kinase domain-like protein(MLKL),p-MLKL,dynamin-related protein 1(DRP1),phosphoglycerate mutase 5(PGAM5)and high mobility group box 1(HMGB1)(P<0.05)after ETEC infection.Moreover,PCA and Que reduced protein abundance of nod-like receptor protein 3(NLRP3),nod-like receptors family CARD domain-containing protein 4(NLRC4),apoptosis-associated speck-like protein containing a CARD(ASC),gasdermin D(GSDMD)and caspase-1(P<0.05)after ETEC infection.Conclusions:In general,our data suggest that PCA and Que are capable of attenuating ETEC-caused intestinal inflammation and damage via inhibiting necroptosis and pyroptosis signaling pathways.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Probiotics: Shaping the gut immunological responses

Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and yeasts.Most of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological responses.Chronic intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal damage.Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue microenvironment.This influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential nutrients.We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function

BACKGROUND Autism spectrum disorder(ASD)is a developmental disorder characterized by social deficits and repetitive behavior.Gastrointestinal(GI)problems,such as constipation,diarrhea,and inflammatory bowel disease,commonly occur in patients with ASD.Previously,GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission.AIM To explore whether GI problems in ASD are related to maternal intestinal inflam-mation and gut microbiota abnormalities.METHODS An ASD rat model was developed using valproic acid(VPA).Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes.RESULTS VPA exposure during pregnancy led to pathological maternal intestinal changes,resulting in alterations in maternal gut microbiota.Additionally,the levels of inflammatory factors also increased.Moreover,prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of infla-mmatory factors.CONCLUSION GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality.Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Helminth infections and intestinal inflammation

Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichuris suis ) have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD.

Fructo-oligosaccharide intensifies visceral hypersensitivity and intestinal inflammation in a stress-induced irritable bowel syndrome mouse model

AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.

Tryptophan:A gut microbiota-derived metabolites regulating inflammation

Inflammatory bowel diseases(IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions over the world. The etiology of IBD is still not well defined, but evidence suggest that it results from per-turbation of the homeostasis between the intestinal microbiota and the mucosal immune system, with the involvement of both genetic and environmental factors. Genome wide association studies, which involve large-scale genome-wide screening of potential polymorphism, have identified several mutations associated with IBD. Among them, Card9, a gene encoding an adapter molecule involved in innate immune response to fungi(via type C-lectin sensing) through the activation of IL-22 signaling pathway, has been identified as one IBD susceptible genes. Dietary compounds, which represent a source of energy and metabolites for gut bacteria, are also appreciated to be important actors in the etiology of IBD, for example by altering gut microbiota composition and by regulating the generation of short chain fatty acids. A noteworthy study published in the June 2016 issue of Nature Medicine by Lamas and colleagues investigates the interaction between Card9 and the gut microbiota in the generation of the microbiota-derived tryptophan metabolite. This study highlights the role of tryptophan in dampening intestinal inflammation in susceptible hosts.

Sulforaphane attenuates dextran sodium sulphate induced intestinal inflammation via IL-10/STAT3 signaling mediated macrophage phenotype switching

Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.

Fatty acids, inflammation and intestinal health in pigs

The intestine is not only critical for nutrient digestion and absorption, but also is the largest immune organ in the body.However, in pig production, inflammation induced by numerous factors, such as pathogen infection and stresses（e.g.,weaning）, results in intestinal mucosal injury and dysfunction, and consequently results in poor growth of pigs. Dietary fatty acids not only play critical roles in energy homeostasis and cel ular membrane composition, but also exert potent effects on intestinal development, immune function, and inflammatory response. Recent studies support potential therapeutic roles for specific fatty acids（short chain and medium chain fatty acids and long chain polyunsaturated fatty acids） in intestinal inflammation of pigs. Results of these new lines of work indicate trophic and cytoprotective effects of fatty acids on intestinal integrity in pigs. In this article, we review the effect of inflammation on intestinal structure and function, and the role of specific fatty acids on intestinal health of pigs, especial y under inflammatory conditions.

Side-stream smoking reduces intestinal inflammation and increases expression of tight junction proteins

AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.

Supplemental N-acyl homoserine lactonase alleviates intestinal disruption and improves gut microbiota in broilers challenged by Salmonella Typhimurium

Background Salmonella Typhimurium challenge causes a huge detriment to chicken production.N-acyl homoserine lactonase(AHLase),a quorum quenching enzyme,potentially inhibits the growth and virulence of Gram-negative bacteria.However,it is unknown whether AHLase can protect chickens against S.Typhimurium challenge.This study aimed to evaluate the effects of AHLase on growth performance and intestinal health in broilers challenged by S.Typhimurium.A total of 240 one-day-old female crossbred broilers(817C)were randomly divided into 5 groups(6 replicates/group):negative control(NC),positive control(PC),and PC group supplemented with 5,10 or 20 U/g AHLase.All birds except those in NC were challenged with S.Typhimurium from 7 to 9 days of age.All parameters related to growth and intestinal health were determined on d 10 and 14.Results The reductions(P<0.05)in body weight(BW)and average daily gain(ADG)in challenged birds were alleviated by AHLase addition especially at 10 U/g.Thus,samples from NC,PC and PC plus 10 U/g AHLase group were selected for further analysis.S.Typhimurium challenge impaired(P<0.05)intestinal morphology,elevated(P<0.05)ileal inflammatory cytokines(IL-1βand IL-8)expression,and increased(P<0.05)serum diamine oxidase(DAO)activity on d 10.However,AHLase addition normalized these changes.Gut microbiota analysis on d 10 showed that AHLase reversed the reductions(P<0.05)in several beneficial bacteria(e.g.Bacilli,Bacillales and Lactobacillales),along with increases(P<0.05)in certain harmful bacteria(e.g.Proteobacteria,Gammaproteobacteria,Enterobacteriaceae and Escherichia/Shigel a)in PC group.Furthermore,AHLase-induced increased beneficial bacteria and decreased harmful bacteria were basically negatively correlated(P<0.05)with the reductions of ileal IL-1βand IL-8 expression and serum DAO activity,but positively correlated(P<0.05)with the increased BW and ADG.Functional prediction revealed that AHLase abolished S.Typhimurium-induced upregulations(P<0.05)of certain pathogenicity-related pathways such as lipopolysaccharide biosynthesis,shigellosis,bacterial invasion of epithelial cells and pathogenic Escherichia coli infection of gut microbiota.Conclusions Supplemental AHLase attenuated S.Typhimurium-induced growth retardation and intestinal disruption in broilers,which could be associated with the observed recovery of gut microbiota dysbiosis.

Transcriptome Analysis Reveals the Regulation Role of miR-144-5p in Intestinal Immunity of Japanese Flounder(Paralichthys olivaceus)

MicroRNAs(miRNAs),22-nucleotide-long micromanagers that guide the post-transcriptional regulation of a wide range of target genes,can theoretically be used as a diagnostic or therapeutic target for inflammatory reaction.In fish,miR-144-5p expression varies dramatically in response to the different bacterial infections and can regulate immunity-related genes to reduce the occurrence of inflammation.In this research,the regulation function of miR-144-5p to the intestinal innate immunity was udied in flounder Paralichthys olivaceus.The flounders were interfered by 2μg g^(-1) miR-144-5p antagomir and their tissues(intestine,liver and spleen)were harvested from the fish at 12 h post-injection.More than 60 million high-quality reads were collected.At 24 hours after miR-144-5p or miR-NC interference,a total of 2704 and 1823 different-expresion genes(DEGs)were identified in comparison with control group,respectively.The DEGs were enriched in a variety of immunity-related signaling pathways,including NOD-like receptor,Wnt and Toll-like receptor signaling pathways,according to GO and KEGG analyses.A total of 503 highly interacting DEGs engaged in 33 immunity-related signaling pathways were discovered using KEGG analyses.Additionally,5 hub genes were found by protein-protein interaction networks,which formed an intricate immune regulation network.Meanwhile,these hub genes were mostly involved in focal adhesion,Wnt signaling pathway,as well as the Intestinal Immune Network for IgT(IgA)Production Pathway.In conclusion,the loss of miR-144-5p can affect immunity-related genes and downstream signaling pathways.Our findings suggest that miR-144-5p is a modulator of gene networks and signaling pathways associated with intestinal innate immunity.

Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier

More and more evidence suggests that puerarin,a potential remedy for gut inflammation,may have an ameliorative effect on sleep disturbances.However,the relationship between puerarin and sleep disruption has not been extensively researched.This study aims to explore the role and mechanisms of puerarin in improving sleep disorders.We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests.Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver,lung,and kidney.Puerarin reversed multi-organ damage and inflammation.Further,puerarin activated paneth cells,resulting in increased lysozyme and TGF-βproduction,and stimulating intestinal stem cell proliferation.Puerarin also effectively inhibited the expression of F4/80,iNOS,TNF-α,and IL-1βin the small intestine,while it increased Chil3,CD206,and Arg-1 levels.Moreover,puerarin treatment significantly decreased P-P65,TLR4,Bcl-xl,and cleaved caspase-3 protein levels while increasing barrier protein levels,including ZO-1,Occludin,Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut.Overall,puerarin diminished systemic inflammation,particularly intestinal inflammation,and enhanced intestinal barrier integrity in mice with sleep disorders.Our findings suggest a potential new therapeutic pathway for sleep disorders.

Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance

The intestinal mucus barrier is an important line of defense against gut pathogens.Damage to this barrier brings bacteria into close contact with the epithelium,leading to intestinal inflammation.Therefore,its restoration is a promising strategy for alleviating intestinal inflammation.This study showed that Abelmoschus manihot polysaccharide(AMP)fortifies the intestinal mucus barrier by increasing mucus production,which plays a crucial role in the AMP-mediated amelioration of colitis.IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10.Moreover,bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila.These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota.This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Association between Exposure to Metals during Pregnancy,Childhood Gut Microbiome,and Risk of Intestinal Inflammation in Late Childhood

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease.Nonetheless,how prenatal exposure to metals eventually results in long-term effects on the gut microbiome,leading to subclinical intestinal inflammation,particularly during late childhood,has not been studied.It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation.We used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy(metal−microbial clique signature)had a higher likelihood of intestinal inflammation,measured based on fecal calprotectin(FC)in late childhood.We obtained samples from a well-characterized longitudinal birth cohort from Mexico City(n=108),Mexico.In the second and third trimesters of pregnancy,11 metals were measured in whole blood.Gut microbial abundances and FC were measured in stool samples from children 9−11 years of age.Elevated FC was defined as having FC above 100μg/g of stool.We identified subgroups of children in whom microbial and metal−microbial clique signatures were associated with elevated FC(false discovery rate(FDR)<0.05).In particular,we found two metal−microbial clique signatures significantly associated with elevated FC:(1)low cesium(Cs)and copper(Cu)in the third trimester and low relative abundance of Eubacterium ventriosum(OR[95%CI]:10.27[3.57,29.52],FDR<0.001)and(2)low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDR<0.05).This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood,denoting an elevated risk of intestinal inflammation.

Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy

BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.

Changing face of irritable bowel syndrome

Recent years have witnessed tremendous progress in our understanding of irritable bowel syndrome （IBS）. It is evident that this is a truly global disease associated with significant symptoms and impairments in personal and social functioning for afflicted individuals. Advances in our understanding of gut flora-mucosal interactions, the enteric nervous system and the brain-gut axis have led to substantial progress in the pathogenesis of symptoms in IBS and have provided some hints towards the basic etiology of this disorder, in some subpopulations, at the very least. We look forward to a time when therapy will be addressed to pathophysiology and perhaps, even to primary etiology. In the meantime, a model based on a primary role for intestinal inflammation serves to integrate the various strands, which contribute to the presentation of IBS