BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study...BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.展开更多
Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environment...Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environmental factors,plays a crucial role in host adaptability and may facilitate local adaptation within species.Concurrently,the genetic background of host populations influences gut microbiome composition,highlighting the bidirectional relationship between host and microbiome.Despite this,our understanding of gut microbiome plasticity and its role in host adaptability remains limited,particularly in reptiles.To clarify this issue,we conducted a reciprocal translocation experiment with gravid females of the Qinghai toad-headed lizards(Phrynocephalus vlangalii)between high-altitude(2?600 m a.s.l.)and superhigh-altitude(3?600 m a.s.l.)environments on Dangjin Mountain of the Qinghai-Xizang Plateau,China.One year later,we assessed the phenotypes and gut microbiomes of their offspring.Results revealed significant plasticity in gut microbiome diversity and structure in response to contrasting elevations.Highaltitude conditions increased diversity,and maternal effects appeared to enable high-altitude lizards to maintain elevated diversity when exposed to superhigh-altitude environments.Additionally,superhigh-altitude lizards displayed distinct gut microbiome structures with notable host specificity,potentially linked to their lower growth rates.Overall,these findings underscore the importance of the gut microbiome in facilitating reptilian adaptation to rapid environmental changes across altitudinal gradients.Furthermore,this study provides critical insights into microbial mechanisms underpinning local adaptation and adaptative plasticity,offering a foundation for future research on host-microbiome interactions in evolutionary and ecological contexts.展开更多
The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curc...The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.展开更多
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...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.展开更多
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...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.展开更多
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 inf...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.展开更多
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 chron...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.展开更多
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 r...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.展开更多
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...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.展开更多
The gut microbiome,a complex ecosystem of microorganisms in the digestive tract,has emerged as a critical factor in human health,influencing metabolic,immune,and neurological functions.This review explores the connect...The gut microbiome,a complex ecosystem of microorganisms in the digestive tract,has emerged as a critical factor in human health,influencing metabolic,immune,and neurological functions.This review explores the connection between the gut microbiome and orthopedic health,examining how gut microbes impact bone density,joint integrity,and skeletal health.It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis,suggesting microbiome modulation as a potential therapeutic strategy.Key findings include the microbiome’s role in bone metabolism through hormone regulation and production of short-chain fatty acids,crucial for mineral absorption.The review also considers the effects of diet,probiotics,and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health.While promising,challenges in translating microbiome research into clinical practice persist,necessitating further exploration and ethical consideration of microbiome-based therapies.This interdisciplinary research aims to link digestive health with musculoskeletal integrity,offering new insights into the prevention and management of bone and joint diseases.展开更多
Adaptative strategies of the frog, Nanorana parkeri, to extreme environments at high altitude are linked with the evolution of their own genetic mechanisms and phenotypic traits. However, to date, the roles of symbiot...Adaptative strategies of the frog, Nanorana parkeri, to extreme environments at high altitude are linked with the evolution of their own genetic mechanisms and phenotypic traits. However, to date, the roles of symbiotic microbiomes in host adaptation to environmental extremes remain enigmatic. In the present study, the 16S rRNA gene amplicon coupled with metagenomic sequencing was used to explore composition as well as potential functions of microbiomes in the gut of N. parkeri collected at both low(3 400 m above sea level(a.s.l.)) and high(4 600 m a.s.l.)altitudes on the Qinghai-Xizang Plateau. We found that the phylum Firmicutes and genera,such as unclassified_Peptostreptococcaceae,unclassified_Lachnospiraceae, Breznakia, and unclassified_Ruminococcaceae, dominated the core gut microbiomes at both altitudes. High-altitude frogs have a lower alpha diversity of gut microbiome than low-altitude individuals. Moreover, two potentially butyrate-producing bacterial genera, Anaerovorax and Pygmaiobacter, exhibited higher relative abundances in high-altitude individuals versus low-altitude frogs.Notably, at high altitude, families such as antibacterial GH90 and GT103, associated with inflammation attenuation, showed a significantly high relative abundance, whereas GT48, contributing to the synthesis of fungal cell walls, exhibited a significant decrease in the relative abundance. The current study provides novel insights into the role of gut microbiomes in the adaptation of amphibians to high-altitude environments.展开更多
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 wh...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.展开更多
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,t...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.展开更多
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 microbiom...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.展开更多
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; rang...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.展开更多
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...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.展开更多
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 r...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.展开更多
Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to ...Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to the liver via the portal vein,and has recently been identified as a predictor of liver disease state.Studies in NAFLD,cirrhosis and HCC have identified certain microbial signatures associated with these diseases,with the disease-associated microbiome changes collectively referred to as dysbiosis.The pathophysiologic underpinnings of these observations are an area of ongoing investigation,with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability(leaky gut)and activation of the innate immune system.In the innate immune system,pathogen recognition receptors(Toll like receptors)on resident liver cells and macrophages cause liver inflammation,fibrosis,hepatocyte proliferation and reduced antitumor immunity,leading to chronic liver disease and carcinogenesis.Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR(nuclear receptor),which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease.Longitudinal experimental and clinical studies are needed in different populations to examine these questions further.The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet,probiotics,fecal microbiota transplantation and prebiotics in improving liver disease in experimental models.Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis.The microbial profile is different in responders to cancer immunotherapy including liver cancer,but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.展开更多
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 g...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.展开更多
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 ...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.展开更多
文摘BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.
基金supported by the National Natural Science Foundation of China (31861143023,31872252)Strategic Priority Research Program of the Chinese Academy of Sciences (XDA20050201)。
文摘Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environmental factors,plays a crucial role in host adaptability and may facilitate local adaptation within species.Concurrently,the genetic background of host populations influences gut microbiome composition,highlighting the bidirectional relationship between host and microbiome.Despite this,our understanding of gut microbiome plasticity and its role in host adaptability remains limited,particularly in reptiles.To clarify this issue,we conducted a reciprocal translocation experiment with gravid females of the Qinghai toad-headed lizards(Phrynocephalus vlangalii)between high-altitude(2?600 m a.s.l.)and superhigh-altitude(3?600 m a.s.l.)environments on Dangjin Mountain of the Qinghai-Xizang Plateau,China.One year later,we assessed the phenotypes and gut microbiomes of their offspring.Results revealed significant plasticity in gut microbiome diversity and structure in response to contrasting elevations.Highaltitude conditions increased diversity,and maternal effects appeared to enable high-altitude lizards to maintain elevated diversity when exposed to superhigh-altitude environments.Additionally,superhigh-altitude lizards displayed distinct gut microbiome structures with notable host specificity,potentially linked to their lower growth rates.Overall,these findings underscore the importance of the gut microbiome in facilitating reptilian adaptation to rapid environmental changes across altitudinal gradients.Furthermore,this study provides critical insights into microbial mechanisms underpinning local adaptation and adaptative plasticity,offering a foundation for future research on host-microbiome interactions in evolutionary and ecological contexts.
文摘The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.
文摘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.
基金funds by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),China(Grant No.:2022-I2M-1e014)the National Natural Science Foundation of China(Grant No.:82293684)+1 种基金Beijing Natural Science Foundation,China(Grant No.:L232084)the National Key R&D Program of China(Grant No.:2022YFA0806400).
文摘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.
基金Supported by the Songjiang District Tackling Key Science and Technology Research Projects,No.20sjkjgg32the Excellent Young Talents Training Program of Songjiang Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,No.QNRC-004Science and Technology Project of Songjiang District,No.22SJKJGG81。
文摘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.
基金National Key Research and Development Program of China(2022YFC2303100)Central Plains Talent Program-Central Plains Youth Top Talents,the Young and Middle-aged Academic Leaders of Henan Provincial Health Commission(HNSWJW-2022013)+1 种基金Funding for Scientific Research and Innovation Team of the First Affiliated Hospital of Zhengzhou University(QNCXTD2023002 and ZYCXTD2023002)Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022001A and JNL-2022015B).
文摘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.
基金supported by the key project of the Natural Science Foundation of Chongqing(cstc2020jcyj-zdxmX0029)the Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN202100412).
文摘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.
基金supported by the Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)。
文摘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.
文摘The gut microbiome,a complex ecosystem of microorganisms in the digestive tract,has emerged as a critical factor in human health,influencing metabolic,immune,and neurological functions.This review explores the connection between the gut microbiome and orthopedic health,examining how gut microbes impact bone density,joint integrity,and skeletal health.It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis,suggesting microbiome modulation as a potential therapeutic strategy.Key findings include the microbiome’s role in bone metabolism through hormone regulation and production of short-chain fatty acids,crucial for mineral absorption.The review also considers the effects of diet,probiotics,and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health.While promising,challenges in translating microbiome research into clinical practice persist,necessitating further exploration and ethical consideration of microbiome-based therapies.This interdisciplinary research aims to link digestive health with musculoskeletal integrity,offering new insights into the prevention and management of bone and joint diseases.
文摘Adaptative strategies of the frog, Nanorana parkeri, to extreme environments at high altitude are linked with the evolution of their own genetic mechanisms and phenotypic traits. However, to date, the roles of symbiotic microbiomes in host adaptation to environmental extremes remain enigmatic. In the present study, the 16S rRNA gene amplicon coupled with metagenomic sequencing was used to explore composition as well as potential functions of microbiomes in the gut of N. parkeri collected at both low(3 400 m above sea level(a.s.l.)) and high(4 600 m a.s.l.)altitudes on the Qinghai-Xizang Plateau. We found that the phylum Firmicutes and genera,such as unclassified_Peptostreptococcaceae,unclassified_Lachnospiraceae, Breznakia, and unclassified_Ruminococcaceae, dominated the core gut microbiomes at both altitudes. High-altitude frogs have a lower alpha diversity of gut microbiome than low-altitude individuals. Moreover, two potentially butyrate-producing bacterial genera, Anaerovorax and Pygmaiobacter, exhibited higher relative abundances in high-altitude individuals versus low-altitude frogs.Notably, at high altitude, families such as antibacterial GH90 and GT103, associated with inflammation attenuation, showed a significantly high relative abundance, whereas GT48, contributing to the synthesis of fungal cell walls, exhibited a significant decrease in the relative abundance. The current study provides novel insights into the role of gut microbiomes in the adaptation of amphibians to high-altitude environments.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by National Science and Technology Major Project of China,No.2018ZX10302206.
文摘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.
基金Chan Zuckerberg Biohub Physician Scientist Scholar Awardand National Institutes of Health NIDDK Clinical Research Loan Repayment Program Award.
文摘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.
文摘Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to the liver via the portal vein,and has recently been identified as a predictor of liver disease state.Studies in NAFLD,cirrhosis and HCC have identified certain microbial signatures associated with these diseases,with the disease-associated microbiome changes collectively referred to as dysbiosis.The pathophysiologic underpinnings of these observations are an area of ongoing investigation,with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability(leaky gut)and activation of the innate immune system.In the innate immune system,pathogen recognition receptors(Toll like receptors)on resident liver cells and macrophages cause liver inflammation,fibrosis,hepatocyte proliferation and reduced antitumor immunity,leading to chronic liver disease and carcinogenesis.Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR(nuclear receptor),which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease.Longitudinal experimental and clinical studies are needed in different populations to examine these questions further.The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet,probiotics,fecal microbiota transplantation and prebiotics in improving liver disease in experimental models.Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis.The microbial profile is different in responders to cancer immunotherapy including liver cancer,but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.
基金funded by the grants from the National Key R&D Program of China(No.2022YFD1301004)National Natural Science Foundation of China(No.31601962)+1 种基金Fundamental Research Funds for the Central Universities(2662019QD021)Key Laboratory of Molecular Animal Nutrition of Zhejiang University(KLMAN202101 and KLMAN202205)。
文摘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.
文摘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.
