Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease

The intestinal microbiota, which evolved over tens of thousands of years along with their human hosts, constitutes a complex and diverse ecosystem whose composition differs from person to person. Accumulating evidence indicates that commensal bacteria exert numerous beneficial physiological effects for humans, including nutrition, protection, metabolism, organ development and immunomodulation. However, mucosal immune responses to intestinal microflora require precise control to allow appropriate defense against potential pathogens but restrict the immune response to beneficial resident bacteria. The task of intestinal homeostasis is accomplished by epithelium and specialized immune system in the gastrointestinal tract. Alternation in the composition of the bacterial community, consisting of increased representation of harmful species or under presence of protective species, or dysbiosis has been linked to various chronic and inflammatory disorders, such as inflammatory bowel disease. An improved understanding of the underlying molecular mechanisms of host-microorganism interactions could bring new insights into onset and pathogenesis of several autoimmune diseases. This review will discuss physiologic properties of commensal microbiota and how dysregulated immune responses to them contribute to chronic mucosal inflammation.

Gut microbiota,inflammatory bowel disease and colorectal cancer

The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and carcinogenesis.The increase in some specific groups of harmful bacteria,such as Escherichia coli(E.coli)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD patients.Therefore,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated CRC.Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand Bacteroidetes.Specific bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,E.coli,Enterococcus faecalis,Streptococcus gallolyticus,and ETBF.Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.

Resveratrol and its derivates improve inflammatory bowel disease by targeting gut microbiota and inflammatory signaling pathways

Inflammatory bowel disease(IBD)is a chronic inflammatory lesion of the intestine,mainly manifested by infiltration of intestinal inflammatory cells and imbalance of gut microbiota.Conventional treatments for IBD include antibiotics,immunosuppressive agents,5-aminosalicylic acid,steroids and surgery,which have high toxic side effects.Resveratrol is a natural polyphenol,and its various derivatives have anti-oxidation and anti-inflammatory properties.In this paper,we comprehensively review the mechanism of resveratrol and its derivates to alleviate IBD by improving intestinal barrier,regulating the unbalanced gut microbiota,and targeting various inflammatory signaling pathways.

Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease.As a result of the interaction between the liver and the gut microbiota,bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption.With the development of genomics and metabolomics,more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors.Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora,epithelial barrier function,and intestinal immunology.Inflammatory bowel disease can be treated in new ways by using these potential molecules.This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications.In addition,we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.

Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?

Our understanding of the microbial involvement in inflammatory bowel disease(IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity(including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

The protective effect of carnosic acid on dextran sulfate sodium-induced colitis based on metabolomics and gut microbiota analysis

Accumulating evidence suggests that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease(IBD).Carnosic acid(CA)is a major antioxidant component of rosemary and sage.Herein,we investigated the protective effects of dietary CA on dextran sodium sulfate(DSS)-induced colitis mouse model with an emphasis on its impact on the composition and metabolic function of gut microbiota.We found that CA effectively attenuated DSS-stimulated colitis in mice,as evidenced by reduced disease activity index(DAI),and systemic and colonic inflammation.Additionally,CA restored microbial diversity and improved the composition of gut microbiota in DSS-treated mice.Moreover,Spearman’s correlation coefficient showed a significant correlation between the fecal metabolites and the gut microbiota species.Changes in gut microbiota and the correlated metabolites might partially explain CA’s anti-inflammatory effects against colitis.Future clinical trials are needed to determine the therapeutic effects and mechanisms of CA on IBD in humans.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection

Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Pathological and therapeutic interactions between bacteriophages,microbes and the host in inflammatory bowel disease

The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions,a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease(IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition,the immune system and environmental factors. In the recent years,metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review,we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD,hostmicrobe interactions and therapeutic possibilities using bacteria in IBD. Moreover,an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.

Antioxidant and anti-inflammatory roles of tea polyphenols in inflammatory bowel diseases

Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.

Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis

AIM To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC) and ulcerative colitis(UC).METHODS Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with(n = 32) or without(n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16 S ribosomal RNA gene were sequenced on Illumina Mi Seq platform to cover low taxonomic levels. Data were further processed in QIIME employing Ma As Lin and LEf Se tools for analysis of the output data.RESULTS Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease(IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.CONCLUSION PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes(PSC-IBD and UC).

More on the interplay between gut microbiota,autophagy,and inflammatory bowel disease is needed

The concept of inflammatory bowel disease(IBD),which encompasses Crohn’s disease and ulcerative colitis,represents a complex and growing global health concern resulting from a multifactorial etiology.Both dysfunctional autophagy and dysbiosis contribute to IBD,with their combined effects exacerbating the related inflammatory condition.As a result,the existing interconnection between gut microbiota,autophagy,and the host’s immune system is a decisive factor in the occurrence of IBD.The factors that influence the gut microbiota and their impact are another important point in this regard.Based on this initial perspective,this manuscript briefly highlighted the intricate interplay between the gut microbiota,autophagy,and IBD pathogenesis.In addition,it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context.Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms,which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Bacterial biofilms in human gastrointestinal tract: An intricate balance between health and inflammatory bowel diseases

Inflammatory bowel disease (IBD) has been a worldwide health problem. It is characterized by severe intestinal inflammation due to immune responses against the gut microbes in genetically susceptible individuals. The understanding of gut microbiota for its composition and complex interaction in normal and diseased conditions has been assisted by the use of molecular, metagenomics and meta transcriptomics studies. The alteration of intestinal microbiota is the key determinant in the degree of inflammation caused and the prolonged course of disease. The relationship between luminal gut bacteria and innate immunity is also of prime significance. Such developments have further led to the search of specific (including bacteria and fungi) as a causative agent of IBD. Although detailed research has been done for the role of gut microbiota in IBD, molecular mechanisms and related gene expression are still not well understood in this disease, which hampers the generation of effective therapeutic agents for IBD. This paper assessed various factors contributing to IBD, genetic dysbiosis and pathogenic influence in the gut microbiota, interactions such as microbiome-host immune system interaction and microbe-microbe interactions involved in IBD, currently available IBD therapies, followed by a detailed review on bacterial infections that might be involved in IBD, globally and specifically in India.

Neuroimmunomodulation by gut bacteria:Focus on inflammatory bowel diseases

Microbes colonize the gastrointestinal tract are considered as highest complex ecosystem because of having diverse bacterial species and 150 times more genes as compared to the human genome.Imbalance or dysbiosis in gut bacteria can cause dysregulation in gut homeostasis that subsequently activates the immune system,which leads to the development of inflammatory bowel disease(IBD).Neuromediators,including both neurotransmitters and neuropeptides,may contribute to the development of aberrant immune response.They are emerging as a regulator of inflammatory processes and play a key role in various autoimmune and inflammatory diseases.Neuromediators may influence immune cell’s function via the receptors present on these cells.The cytokines secreted by the immune cells,in turn,regulate the neuronal functions by binding with their receptors present on sensory neurons.This bidirectional communication of the enteric nervous system and the enteric immune system is involved in regulating the magnitude of inflammatory pathways.Alterations in gut bacteria influence the level of neuromediators in the colon,which may affect the gastrointestinal inflammation in a disease condition.Changed neuromediators concentration via dysbiosis in gut microbiota is one of the novel approaches to understand the pathogenesis of IBD.In this article,we reviewed the existing knowledge on the role of neuromediators governing the pathogenesis of IBD,focusing on the reciprocal relationship among the gut microbiota,neuromediators,and host immunity.Understanding the neuromediators and host-microbiota interactions would give a better insight in to the disease pathophysiology and help in developing the new therapeutic approaches for the disease.

Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease

Crohn’s disease(CD)is a chronic,non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease(IBD).CD is prone to relapse,and its incidence displays a persistent increase in developing countries.However,the pathogenesis of CD is poorly understood,with some studies emphasizing the link between CD and the intestinal microbiota.Specifically,studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD.Furthermore,investigations have shown whitematter lesions and neurologic deficits in patients with IBD.Based on these findings,brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging(BOLD-f MRI).BOLD-f MRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates.Therefore,biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients.To further study this phenomenon,brain changes of CD patients can be detected non-invasively,effectively and accurately by BOLD-f MRI combined with magnetic resonance spectroscopy(MRS).This approach can further shed light on the mechanisms of the occurrence and development of neurological CD.Overall,this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner

Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD.Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed.Herein,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2)ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma model.Together,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

Potential of the ellagic acid-derived gut microbiota metabolite–Urolithin A in gastrointestinal protection

Urolithin A(UA)is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria.The physiologically relevant micromolar concentrations of UA,achieved in the plasma and gastrointestinal tract(GI)after consumption of its dietary precursors,have been revealed to offer GI protection.The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects.UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity,including those involved in carcinogen biotransformation and antioxidant defense.The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract.The data presented herein,covering both studies on the pure compound and in vivo generated UA form its natural precursor,support the potential of this metabolite in treatment interventions against GI ailments.

Gossip in the gut: Quorum sensing, a new player in the hostmicrobiota interactions

Bacteria are known to communicate with each other and regulate their activities in social networks by secreting and sensing signaling molecules called autoinducers,a process known as quorum sensing(QS).This is a growing area of research in which we are expanding our understanding of how bacteria collectively modify their behavior but are also involved in the crosstalk between the host and gut microbiome.This is particularly relevant in the case of pathologies associated with dysbiosis or disorders of the intestinal ecosystem.This review will examine the different QS systems and the evidence for their presence in the intestinal ecosystem.We will also provide clues on the role of QS molecules that may exert,directly or indirectly through their bacterial gossip,an influence on intestinal epithelial barrier function,intestinal inflammation,and intestinal carcinogenesis.This review aims to provide evidence on the role of QS molecules in gut physiology and the potential shared by this new player.Better understanding the impact of intestinal bacterial social networks and ultimately developing new therapeutic strategies to control intestinal disorders remains a challenge that needs to be addressed in the future.

Spinal anesthesia alleviates dextran sodium sulfate-induced colitis by modulating the gut microbiota

BACKGROUND Inflammatory bowel disease(IBD)is a chronic disease with recurrent intestinal inflammation.Although the exact etiology of IBD remains unknown,the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors.The role of the gut microbiota,particularly the bidirectional interaction between the brain and gut microbiota,has gradually attracted more attention.AIM To investigate the potential effect of spinal anesthesia on dextran sodium sulfate(DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.METHODS A DSS-induced colitis mice model was established.Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation(FMT)to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.RESULTS We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms,including reduced body weight loss,decreased disease activity index score,improved intestinal permeability and colonic morphology,decreased inflammatory response,and enhanced intestinal barrier functions.Moreover,spinal anesthesia significantly increased the abundance of Bacteroidetes,which was suppressed in the gut microbiota of colitis mice.Interestingly,cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes.We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS,which might affect the gut microbiota.CONCLUSION These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota,which highlights a novel approach for the treatment of IBD.