Metabolic syndrome’s new therapy:Supplement the gut microbiome

This letter to the editor discusses the publication on gut microbiome supple-mentation as therapy for metabolic syndrome.Gut microbiome dysbiosis disrupts intestinal bacterial homeostasis and is related to chronic inflammation,insulin resistance,cardiovascular diseases,type 2 diabetes mellitus,and obesity.Previous research has found that increasing the abundance of beneficial microbiota in the gut modulates metabolic syndrome by reducing chronic inflammation and insulin resistance.Prebiotics,probiotics,synbiotics,and postbiotics are often used as supplements to increase the number of beneficial microbes and thus the produc-tion of short-chain fatty acids,which have positive effects on the gut microbiome and metabolic syndrome.In this review article,the author summarizes the available supplements to increase the abundance of beneficial gut microbiota and reduce the abundance of harmful microbiota in patients with metabolic disorders.Our group is also researching the role of the gut microbiota in chronic liver disease.This article will be of great help to our research.At the end of the letter,the mechanism of the gut microbiota in chronic liver disease is discussed.

The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives

Regulation of gut microbiota and its impact on human health is the theme of intensive research.The incidence and prevalence of atrial fibrillation(AF)are continuously escalating as the global population ages and chronic disease survival rates increase;however,the mechanisms are not entirely clarified.It is gaining awareness that alterations in the assembly,structure,and dynamics of gut microbiota are intimately engaged in the AF progression.Owing to advancements in next-generation sequencing technologies and computational strategies,researchers can explore novel linkages with the genomes,transcriptomes,proteomes,and metabolomes through parallel meta-omics approaches,rendering a panoramic view of the culture-independent microbial investigation.In this review,we summarized the evidence for a bidirectional correlation between AF and the gut microbiome.Furthermore,we proposed the concept of“gut-immune-heart”axis and addressed the direct and indirect causal roots between the gut microbiome and AF.The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions,which shed light on a definite direction for future experiments.

Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Lactobacillus from fermented bamboo shoots prevents inflammation in DSS-induced colitis mice via modulating gut microbiome and serum metabolites

Fermented bamboo shoots(FBS)is a region-specific food widely consumed in Southwestern China,with Lactobacillus as the predominant fermenting bacteria.However,the probiotic potential of Lactobacillus derived from FBS reminds largely unexplored,especially for diseases with a low prevalence in areas consuming FBS,namely,inflammatory bowel disease.In this study,Lactiplantibacillus pentosus YQ001 and Lentilactobacillus senioris YQ005 were screening by in vitro probiotic tests to further investigate the probioticlike bioactivity in dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse.They exhibited more positive probiotic effects than Lactobacillus rhamnosus GG in preventing intestinal inflammatory response.The results revealed that both strains improved the abundance of deficient intestinal microbiota in UC mice,including Muribaculaceae and Akkermansia.In the serum metabolome,they modulated the DSS-disturbed levels of metabolites,with significant increment of cinnamic acid.Meanwhile,they reduced the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6)inflammatory factors and increased zonula occludens-1(ZO-1),Occludin,and cathelicidin-related antimicrobial peptide(CRAMP)in the colon.Consequently,these results demonstrated that Lactobacillus spp.isolates derived from FBS showed promising probiotic activity based on the gut microbiome homeostasis modulation,anti-inflammation and intestinal barrier protection in UC mice.

Distinct gut microbiomes in Thai patients with colorectal polyps

BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence[e.g.,tubular adenoma(TA)]often progress to malignancy and are closely associated with changes in the composition of the gut microbiome.There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway,such as hyperplastic polyps(HP).Exploration of microbiome alterations asso-ciated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis.AIM To investigate gut microbiome signatures,microbial associations,and microbial functions in HP and TA patients.METHODS Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps[control group(CT),n=40],patients with HP(n=52),and patients with TA(n=60).Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA.Analytical techniques in this study included differential abundance analysis,co-occurrence network analysis,and differential pathway analysis.RESULTS Colorectal cancer(CRC)-associated bacteria,including Streptococcus gallolyticus(S.gallolyticus),Bacteroides fragilis,and Clostridium symbiosum,were identified as characteristic microbial species in TA patients.Mediterraneibacter gnavus,associated with dysbiosis and gastrointestinal diseases,was significantly differentially abundant in the HP and TA groups.Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively,whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis(e.g.,mevalonate);S.gallolyticus was a major contributor.Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients,whereas TA patients exhibited co-occurrence of CRC-associated bacteria.Furthermore,the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients.CONCLUSION This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development,providing insights concerning the roles of microbial species,functional pathways,and microbial interactions in colorectal carcinogenesis.

Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

Gut microbiome:A revolution in typeⅡdiabetes mellitus

TypeⅡdiabetes mellitus(T2DM)has experienced a dramatic increase globally across countries of various income levels over the past three decades.The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors.While numerous pharmaceutical therapies have been developed,there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects.In this context,the exploration of the gut microbiome presents a promising avenue.Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals,suggesting its potential role in the disease’s pathogenesis and progression.This emerging field offers diverse applications,particularly in modifying the gut environment through the administration of prebiotics,probiotics,and fecal microbiome transfer.These interventions aim to restore a healthy microbiome balance,which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM.Although current results from clinical trials have not yet shown dramatic effects on diabetes management,the groundwork has been laid for deeper investigation.Ongoing and future clinical trials are critical to advancing our understanding of the microbiome’s impact on diabetes.By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism,researchers can develop more targeted interventions.The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM,potentially reducing the disease’s burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic,systemic health improvements.

The Effect of Macronutrient Restrictions on Gut Microbiome and Biochemical Parameters of Wistar Albino Rats

Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.

Update on the gut microbiome in health and diseases

The Human Microbiome Project,Earth Microbiome Project,and next-generation sequencing have advanced novel genome association,host genetic linkages,and pathogen identification.The microbiome is the sum of the microbes,their genetic information,and their ecological niche.This study will describe how millions of bacteria in the gut affect the human body in health and disease.The gut microbiome changes in relation with age,with an increase in Bacteroidetes and Firmicutes.Host and environmental factors affecting the gut microbiome are diet,drugs,age,smoking,exercise,and host genetics.In addition,changes in the gut microbiome may affect the local gut immune system and systemic immune system.In this study,we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases.Due to the high number of publications on the argument,from a methodologically point of view,we decided to select the best papers published in referred journals in the last 3 years.Then we selected the previously published papers.The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

Gut microbiome in alcohol use disorder:Implications for health outcomes and therapeutic strategies-a literature review

Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders.Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD,with alcohol consumption directly impacting its composition and function.This review article aims to explore the intricate relationship between the gut microbiome and AUD,focusing on the implications for mental health outcomes and potential therapeutic strategies.We discuss the bidirectional communication between the gut microbiome and the brain,highlighting the role of microbiotaderived metabolites in neuroinflammation,neurotransmission,and mood regulation.Furthermore,we examine the influence of AUD-related factors,such as alcohol-induced gut dysbiosis and increased intestinal permeability,on mental health outcomes.Finally,we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD,including prebiotics,probiotics,and fecal microbiota transplantation.Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.

Colonization and development of the gut microbiome in calves

Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.

Impact of gut microbiome in the development and treatment of pancreatic cancer:Newer insights

The gut microbiome plays an important role in the variation of pharmacologic response.This aspect is especially important in the era of precision medicine,where understanding how and to what extent the gut microbiome interacts with drugs and their actions will be key to individualizing therapy.The impact of the composition of the gut microbiome on the efficacy of newer cancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell treatment has become an active area of research.Pancreatic adenocarcinoma(PAC)has a poor prognosis even in those with potentially resectable disease,and treatment options are very limited.Newer studies have concluded that there is a synergistic effect for immunotherapy in combination with cytotoxic drugs,in the treatment of PAC.A variety of commensal microbiota can affect the efficacy of conventional chemotherapy and immunotherapy by modulating the tumor microenvironment in the treatment of PAC.This review will provide newer insights on the impact that alterations made in the gut microbial system have in the development and treatment of PAC.

Gut microbiome therapeutic modulation to alleviate drug-induced hepatic damage in COVID-19 patients

Coronavirus disease 2019(COVID-19)infection caused by the severe acute respiratory syndrome coronavirus 2 virus,its symptoms,treatment,and post-COVID-19 effects have been a major focus of research since 2020.In addition to respiratory symptoms,different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases,including liver abnormalities.The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients.The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers.Gut microbiota influences liver chemistry through its metabolites.Gut dysbiosis during COVID-19 treatment can promote liver inflammation.Here,we highlighted the bidirectional association of liver physiology and gut microbiota(gut-liver axis)and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.

Emerging role of the gut microbiome in post-infectious irritable bowel syndrome:A literature review

Post-infectious irritable bowel syndrome(PI-IBS)is a particular type of IBS,with symptom onset after an acute episode of infectious gastroenteritis.Despite infectious disease resolution and clearance of the inciting pathogen agent,10%of patients will develop PI-IBS.In susceptible individuals,the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions.These changes can affect the gut-brain axis and the visceral sensitivity,disrupting the intestinal barrier,altering neuromuscular function,triggering persistent low inflammation,and sustaining the onset of IBS symptoms.There is no specific treatment strategy for PI-IBS.Different drug classes can be used to treat PI-IBS similar to patients with IBS in general,guided by their clinical symptoms.This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms.It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS.The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging.Several studies on PI-IBS animal models reported promising results.However,published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce.Future research is required.

Maintenance of gut microbiome stability for optimum intestinal health in pigs——a review

Pigs are exposed to various challenges such as weaning,environmental stressors,unhealthy diet,diseases and infections during their lifetime which adversely affects the gut microbiome.The inability of the pig microbiome to return to the pre-challenge baseline may lead to dysbiosis resulting in the outbreak of diseases.Therefore,the maintenance of gut microbiome diversity,robustness and stability has been influential for optimum intestinal health after perturbations.Nowadays human and animal researches have focused on more holistic approaches to obtain a robust gut microbiota that provides protection against pathogens and improves the digestive physiology and the immune system.In this review,we present an overview of the swine gut microbiota,factors affecting the gut microbiome and the importance of microbial stability in promoting optimal intestinal health.Additionally,we discussed the current understanding of nutritional interventions using fibers and pre/probiotics supplementation as non-antibiotic alternatives to maintain microbiota resilience to replace diminished species.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Background:Due to the outbreak and rapid spread of coronavirus disease 2019(COVID-19),more than 160 million patients have become convalescents worldwide to date.Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19.However,it is unknown whether their characteristics return to normal after the 1-year recovery.Methods:We recruited 35 confirmed patients to provide specimens at discharge and 1 year later,as well as 160healthy controls.A total of 497 samples were prospectively collected,including 219 tongue-coating,129 stool and 149 plasma samples.Tongue-coating and stool samples were subjected to 16S rRNA sequencing,and plasma samples were subjected to untargeted metabolomics testing.Results:The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal.In the recovery process,the microbial diversity gradually increased.Butyric acid-producing microbes and Bifidobacterium gradually increased,whereas lipopolysaccharideproducing microbes gradually decreased.In addition,sphingosine-1-phosphate,which is closely related to the inflammatory factor storm of COVID-19,increased significantly during the recovery process.Moreover,the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later.Conclusions:This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19.The key microbiome and metabolites in the process of recovery were identified,and provided new treatment ideas for accelerating recovery.And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Gut microbiome and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally and imposed a heavy economic burden on society and individuals.To date,the pathological process of NAFLD is not yet fully elucidated.Compelling evidences have demonstrated the pivotal role of gut microbiota in the pathogenesis of NAFLD,and gut dysbiosis has been commonly observed in patients with NAFLD.Gut dysbiosis impairs gut permeability,allowing the translocation of bacterial products such as lipopolysaccharides(LPS),short-chain fatty acids(SCFAs),and ethanol to the liver via portal blood flow.This review aimed to shed light on the underlying mechanisms by which gut microbiota influences the development and progression of NAFLD.In addition,the potential application of gut microbiome as a non-invasive diagnostic tool and a novel therapeutical target was reviewed.

Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.

Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Antimicrobial peptides(AMP)are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells,Paneth cells,as well as immune cells in the gastrointestinal(GI)tract.They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections.Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease(IBD)and converge on the function of AMP,the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years.In this frontier article,we discuss the function and mechanisms of AMP in the GI tract,examine the interaction of AMP with the gut microbiome,explore the role of AMP in the pathogenesis of IBD,and review translational applications of AMP in patients with IBD.

Role of bile acids in liver diseases mediated by the gut microbiome

The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.