Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by...Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.展开更多
Blueberry anthocyanins(VA)and blackberry anthocyanins(RA)showed benefits on metabolic syndrome(MS)induced by high-fat diet(HFD)in mice.In this study,we investigated whether the therapeutic effects of VA and RA were ac...Blueberry anthocyanins(VA)and blackberry anthocyanins(RA)showed benefits on metabolic syndrome(MS)induced by high-fat diet(HFD)in mice.In this study,we investigated whether the therapeutic effects of VA and RA were achieved by the gut microbiota regulation and whether these effects could be replicated through fecal microbiota transplantation(FMT)using the HFD caused MS model in pseudo-germ-free mice.The results demonstrated that the beneficial effects of VA and RA on MS,including reducing body weight gain and fat accumulation,improving glucose and lipid metabolism,and mitigating intestinal barrier damage,were attributed to the gut microbiota and could be replicated by FMT.16S r RNA sequencing analysis suggested that FMT from donor mice supplemented with VA and RA could regulate the gut microbiota composition.Particularly,FMT from RA supplemented mice displayed the potential to restore the diversity of gut microbiota and the ratio of Firmicutes to Bacteroidetes.Meanwhile,FMT from VA supplemented mice appeared to exert its effects by selectively influencing specific gut microbiota,such as the genus Akkermansia.Furthermore,our analysis identified 10 common differential amplicon sequence variants(ASVs)among groups compared to HFD-HFD group.Notably,ASV_36450 was negatively associated with metabolic parameters,suggesting that Lactobacillus might be the potential bacteria in regulating MS.Overall,our study demonstrated that FMT from VA and RA supplemented mice could ameliorate MS induced by HFD in mice through regulating specific gut microbiota.展开更多
Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believe...Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.展开更多
Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glut...Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.展开更多
Crohn’s disease(CD)is an idiopathic,chronic,and recurrent inflammatory condition of the gastrointestinal tract.Recent studies suggest a potential role of gut microbiota in CD,particularly dysbiosis—an imbalance in g...Crohn’s disease(CD)is an idiopathic,chronic,and recurrent inflammatory condition of the gastrointestinal tract.Recent studies suggest a potential role of gut microbiota in CD,particularly dysbiosis—an imbalance in gut bacteria.While dysbiosis is consistently observed in CD,it remains uncertain whether it is a cause or a consequence of the disease.Given its association with CD,the therapeutic potential of fecal microbiota transplantation(FMT)has been explored.This review examines the role of gut microbiota in CD,evaluates the therapeutic potential of probiotics and FMT,and highlights current research findings and limitations.Key studies on the relationship between gut dysbiosis,probiotics,and FMT in CD were analyzed,with a focus on randomized trials,meta-analyses,and clinical observations.Dysbiosis is a consistent feature of CD,but its causative role remains unclear.Probiotics,prebiotics,and synbiotics have shown no efficacy in inducing or maintaining remission in CD.FMT shows potential as a therapeutic option for CD,but its efficacy remains inconsistent and inconclusive.The variability in outcomes,including diminished effects over time despite repeated FMT,underscores the need for larger,well-controlled trials.Only one randomized controlled trial(RCT)has compared FMT with sham transplantation,but the sample size was very small.Other studies are limited by factors such as small sample sizes,lack of control groups,short follow-up periods,and inconsistent methodologies,making it challenging to draw definitive conclusions.While gut dysbiosis likely plays a role in CD pathogenesis,its causative role remains uncertain.Current evidence does not support FMT as a reliable treatment for inducing or maintaining remission in CD,though it appears generally safe.Larger,standardized,RCTs are necessary to clarify the therapeutic role of FMT in CD management.展开更多
BACKGROUND Simultaneous assessment of gut microbiota in stool and tissue samples is crucial for a better understanding of their role in Crohn’s disease(CD),yet most reports have focused on fecal microbiota alone.Addi...BACKGROUND Simultaneous assessment of gut microbiota in stool and tissue samples is crucial for a better understanding of their role in Crohn’s disease(CD),yet most reports have focused on fecal microbiota alone.Additionally,gut microbiota may serve as a clinically useful diagnostic biomarker of CD although data on this is limited.AIM To evaluate gut microbiota in tissue and stool samples in patients with active CD to understand the structure and function compared to healthy controls(HC).We also assessed their utility as a diagnostic biomarker of CD.METHODS Adult patients with active CD and HC were prospectively recruited for this study.The clinical and investigation details were recorded.Rectal mucosal biopsy and stool samples were obtained to assess the bacterial population.DNA was extracted,the V3-V4 region of the 16S rRNA gene was amplified,and library preparation was done and sequenced on the Illumina MiSeq platform.The bacterial diversity,composition,dysbiosis,predicted function,and predictors of disease state were estimated using the QIIME 2 pipeline and R packages.RESULTS We recruited 66 patients with CD(age 39.7±11.1 years,65.2%males)and 69 HC.Comparison of tissue with fecal microbiota in active CD showed significant differences in composition and predicted function.Both tissue and fecal microbiota from active CD showed reduced microbial diversity and compositional differences compared to HC,and disease state was a key determinant of bacterial population.Differences(CD vs HC)were noted in the abundance of several predicted synthetic and degradation pathways in both tissue and stool bacteria.Tissue microbiota was a superior predictor of active CD than stool(area under receiver operating characteristic curve 0.8 vs 0.62).CONCLUSION Gut microbial characteristics revealed significant structural and functional differences between CD and HC in both tissue and stool.Tissue bacteria performed well as a microbial biomarker for clinical diagnosis of CD.展开更多
Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascul...Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.展开更多
Chronic liver disease has become a global health crisis,with increasing incidence and mortality rates placing a substantial burden on healthcare systems worldwide.A key factor in the progression of chronic liver disea...Chronic liver disease has become a global health crisis,with increasing incidence and mortality rates placing a substantial burden on healthcare systems worldwide.A key factor in the progression of chronic liver disease is intestinal microbiota dysbiosis,which influences liver function via the intricate liver-gut axis.This axis plays a central role in various physiological processes,and disruptions in microbial composition can exacerbate liver pathology.Fecal microbiota transplantation(FMT)has emerged as a promising therapeutic strategy,with the potential to restore the composition and metabolic functions of the intestinal microbiota.Supported by encouraging findings from clinical trials and animal studies,FMT has demonstrated therapeutic benefits,including improvements in clinical symptoms,objective indicators,and long-term prognosis.These benefits encompass reductions in hepatic lipid deposition and inflammation,mitigation of complications in advanced liver disease,promotion of hepatitis B e antigen seroconversion,and enhancement of cognitive function.Although clinical evidence remains preliminary,current data underscore the transformative potential of FMT in managing chronic liver diseases.Nonetheless,challenges persist,including the need for standardized procedures,variability among donors,potential risks,and concerns regarding long-term safety.This review provides a comprehensive evaluation of the current literature on the efficacy and safety of FMT,while exploring future research directions to expand its application in liver disease management.展开更多
Objective To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation(FMT)in patients with type 2 diabetes mellitus(T2DM),and to preliminarily identify the traditional Chinese ...Objective To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation(FMT)in patients with type 2 diabetes mellitus(T2DM),and to preliminarily identify the traditional Chinese medicine(TCM)syndrome element characteristics of FMT in the treatment of T2DM.Methods Between March 25,2023 and September 30,2024,T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine.Participants received oral microbiota capsules as an adjunct to metformin therapy.Information obtained by four diagnostic methods of TCM,along with clinical and laboratory parameters,was collected before and after the intervention.Metagenomic sequencing was employed to analyze the gut microbiota,and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera.According to the post-treatment reduction in glycosylated hemoglobin(HbA1c),patients were categorized into a response(R)group and a non-response(NR)group.Treatment outcomes,safety indicators,gut microbiota changes,and TCM syndrome element features were compared between the two groups.Results A total of 53 T2DM patients were included in the final analysis,and 30 patients were assigned to R group and 23 to NR group.After treatment,the R group exhibited significant reductions in HbA1c,fasting plasma glucose(FPG),and 2-hour postprandial glucose(2hPG)(P<0.05 or P<0.01).The NR group also showed significant decreases in HbA1c and FPG levels P<0.01 or P<0.05.Compared with the NR group,after treatment,FPG level in the R group demonstrated significant reductions(P<0.01).As compared with before treatment,pancreatic islet function demonstrated enhancement in the R group,a significant increase in the 2-hour pastprandial C-peptide(2hC-P)levels in R group(P<0.05),whereas no marked change was observed in the NR group.Regarding body composition indicators,the R group showed significantly lower waist-hip ratio(WHR),visceral fat(VF),and subcutaneous fat(SF)levels compared with the NR group(P<0.01).After treatment,the NR group exhibited a significant elevation in aspartate aminotransferase(AST)levels(P<0.05).Other safety-related indicators fluctuated within normal reference ranges,and no other adverse events,such as diarrhea,fever,or nausea,were reported.Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota,remodeling its overall structure.At the phylum level,the abundance of p_Firmicutes decreased significantly(P<0.01),while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly(P<0.01).At the family level,among the 125 identified taxa,the abundances of f_Bacteroidaceae,f_Lactobacillaceae,and f_Sutterellaceae were significantly elevated,whereas six families,including f_Lachnospiraceae,f_Ruminococcaceae,and f_Coriobacteriaceae,were significantly decreased(all P<0.05).Among the 367 taxa at the genus level,the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella,and significantly decreased abundances in eight genera,including g_Faecalibacterium,g_Ruminococcus,g_Blautia,and g_Collinsella(all P<0.05).Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters,g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide(FC-P)and 2hC-P(P<0.05).HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger(P<0.05)and a significantly negative correlation with g_Bacteroides and g_Collinsella(P>0.05).Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness,phlegm,and Yang deficiency.Before treatment,statistically significant reductions in syndrome element scores were observed for dampness,Yang deficiency,spleen,phlegm,Qi deficiency,Qi stagnation,and Yin deficiency(P<0.01),as well as for heat and liver(P<0.05).The NR group was mainly featured with Qi deficiency and Yin deficiency.Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency(P<0.01),and for spleen,Qi stagnation,liver,and blood deficiency(P<0.05).In this group,the score changes for Yang deficiency,Yin deficiency,heat,and dampness were not statistically significant(P>0.05).Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM.Patients with T2DM presented with specific TCM syndrome element characteristics,notably dampness,phlegm,and Yang deficiency,represent a highly responsive population to FMT therapy.展开更多
Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,...Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.展开更多
AIM To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS A rat model of HE was establis...AIM To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha was examined. RESULTS FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating proinflammatory factors such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. CONCLUSION FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.展开更多
The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbi...The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals.However,there are still no definitive microbial pathogens linked to the onset of IBD.The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients.The special alterations of gut microbiota associated with IBD remain to be evaluated.The microbial interactions and hostmicrobe immune interactions are still not clarified.Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy,few available strains and no standardized administration.Fecal microbiota transplantation(FMT)may restore intestinal microbial ho-meostasis,and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection.Additionally,synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD.However,FMT-related barriers,including the mechanism of restoring gut microbiota,standardized donor screening,fecal material preparation and administration,and long-term safety should be resolved.The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germfree/human flora-associated animals and chemostat gut models.展开更多
Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations....Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.展开更多
BACKGROUND Emerging evidence has demonstrated that fecal microbiota transplantation(FMT)has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis(UC),although the mechan...BACKGROUND Emerging evidence has demonstrated that fecal microbiota transplantation(FMT)has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis(UC),although the mechanism of FMT is unclear.AIM To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota,through association analysis of gut microbiota with colon transcriptome in mice.METHODS Dextran sodium sulfate(DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage.Severity of colon inflammation was measured by body weight,disease activity index,colon length and histological score.Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing.The differentially expressed genes(DEGs)in the colon were obtained by transcriptome sequencing.The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.RESULTS Compared with the DSS group,the weight loss,colon length shortening and inflammation were significantly alleviated in the FMT group.The scores of disease activity index and colon histology decreased obviously after FMT.FMT restored the balance of gut microbiota,especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter.In the transcriptomic analysis,128 DEGs intersected after DSS treatment and FMT.Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation.In the DSS group,there was an increase in colonic T helper CD4^(+)and T cytotoxic CD8^(+)cells by flow cytometry.FMT selectively downregulated the ratio of colonic CD4^(+)and CD8^(+)T cells to maintain intestinal homeostasis.Furthermore,Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G,CCL8 and IDO1.CONCLUSION FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.展开更多
BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations sho...BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and fibrosis.AIM To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in CD.METHODS Intestinal tissue and MAT were collected from 12 patients with CD.Histological manifestations and protein expression levels were analyzed to determine lesion characteristics.Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice.The intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.RESULTS Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota structure.Fetal microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD symptoms.Notably,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and adipokines.Furthermore,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.CONCLUSION Gut microbiota play a critical role in the histopathology of CD.Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.展开更多
With the development of microbiology and metabolomics,the relationship between the intestinal microbiome and intestinal diseases has been revealed.Fecal microbiota transplantation(FMT),as a new treatment method,can af...With the development of microbiology and metabolomics,the relationship between the intestinal microbiome and intestinal diseases has been revealed.Fecal microbiota transplantation(FMT),as a new treatment method,can affect the course of many chronic diseases such as metabolic syndrome,malignant tumor,autoimmune disease and nervous system disease.Although the mechanism of action of FMT is now well understood,there is some controversy in metabolic diseases,so its clinical application may be limited.Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection,and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases.However,the initial results are varied,suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT.The success of FMT depends on the microbial diversity and composition of donor feces.Therefore,clinical trials may fail due to the selection of ineffective donors,and not to faulty indication selection for FMT.A new understanding is that FMT not only improves insulin sensitivity,but may also alter the natural course of type 1 diabetes by modulating autoimmunity.In this review,we focus on the main mechanisms and deficiencies of FMT,and explore the optimal design of FMT research,especially in the field of cardiometabolic diseases.展开更多
To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).METHODSWe searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed litera...To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).METHODSWe searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles.RESULTSA total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration.CONCLUSIONData on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.展开更多
This study aimed to reveal the microbial diversity in the fecal samples of bactrian camels using the 16 S r RNA sequencing analysis on the Illumina Mi Seq platform. Three fecal samples were collected from two geograph...This study aimed to reveal the microbial diversity in the fecal samples of bactrian camels using the 16 S r RNA sequencing analysis on the Illumina Mi Seq platform. Three fecal samples were collected from two geographical regions in China. Operational taxonomic unit（OTU） clustering was performed by identifying an OTU at 97% sequence identity. The alpha and beta diversities were applied to estimate the differences in microbial diversity among the three fecal samples. Totally, 4409, 3151 and 4075 OTUs in the fecal samples were identified in the Lop Nor wild camel（Camelus ferus）, the domestic camel（C. bactrianus） and Dunhuang wild camel（C. ferus）, respectively. The majority of bactreria were affiliated with phylum Firmicutes and Bacteroidetes in the three samples. The wild camels had higher gastrointestinal tract microbial diversity than the domestic one, while the microbial composition of the Lop Nor wild camel shared higher similarity with domestic camel at the genus and family levels than that of the Dunhuang wild camel did. Our results may provide a theoretical basis for assessing their health conditions and may thus be useful for protecting the critically endangered species of C. ferus.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A grow...BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.展开更多
Background:Diarrhea is a major cause of morbidity and mortality in young calves,resulting in considerable economic loss for dairy farms.To determine if some gut microbes might have resistance to dysbiotic process with...Background:Diarrhea is a major cause of morbidity and mortality in young calves,resulting in considerable economic loss for dairy farms.To determine if some gut microbes might have resistance to dysbiotic process with calf diarrhea by dictating the microbial co-occurrence patterns from birth to post-weaning,we examined the dynamic development of the gut microbiota and diarrhea status using two animal trials,with the first trial having 14 Holstein dairy calves whose fecal samples were collected 18 times over 78 d from birth to 15 d post-weaning and the second trial having 43 Holstein dairy calves whose fecal samples were collected daily from 8 to 18 days of age corresponding to the first diarrhea peak of trial 1.Results:Metataxonomic analysis of the fecal microbiota showed that the development of gut microbiota had three age periods with birth and weaning as the separatrices.Two diarrhea peaks were observed during the transition of the three age periods.Fusobacteriaceae was identified as a diarrhea-associated taxon both in the early stage and during weaning,and Clostridium_sensu_stricto_1 was another increased genus among diarrheic calves in the early stage.In the neonatal calves,Prevotella_2(ASV4 and ASV26),Prevotella_9(ASV43),and Alloprevotella(ASV14)were negatively associated with Clostridium_sensu_stricto_1(ASV48),the keystone taxa of the diarrhea-phase module.During weaning,unclassified Muribaculaceae(ASV28 and ASV44),UBA1819(ASV151),Barnesiella(ASV497),and Ruminococcaceae_UCG-005(ASV254)were identified being associated with non-diarrheic status,and they aggregated in the non-diarrhea module of co-occurrence patterns wherein unclassified Muribaculaceae(ASV28)and Barnesiella(ASV497)had a direct negative relationship with the members of the diarrhea module.Conclusions:Taken together,our results suggest that the dynamic successions of calf gut microbiota and the interactions among some bacteria could influence calf diarrhea,and some species of Prevotella might be the core microbiota in both neonatal and weaning calves,while species of Muribaculaceae might be the core microbiota in weaning calves for preventing calf diarrhea.Some ASVs affiliated with Prevotella_2(ASV4 and ASV26),Prevotella_9(ASV43),Alloprevotella(AVS14),unclassified Muribaculaceae(ASV28 and ASV44),UBA1819(ASV151),Ruminococcaceae_UCG-005(ASV254),and Barnesiella(ASV497)might be proper probiotics for preventing calf diarrhea whereas Clostridium_sensu_stricto_1(ASV48)might be the biomarker for diarrhea risk in specific commercial farms.展开更多
基金the 2026 Health Commission Fund of Guizhou Province,China.the freestatistics suite for its technical support.
文摘Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.
基金financially supported by grants from the National Natural Science Foundation of China(32170377,81973463)the Primary Research&Development Plan of Jiangsu Province(BE2020344,BE2022371)。
文摘Blueberry anthocyanins(VA)and blackberry anthocyanins(RA)showed benefits on metabolic syndrome(MS)induced by high-fat diet(HFD)in mice.In this study,we investigated whether the therapeutic effects of VA and RA were achieved by the gut microbiota regulation and whether these effects could be replicated through fecal microbiota transplantation(FMT)using the HFD caused MS model in pseudo-germ-free mice.The results demonstrated that the beneficial effects of VA and RA on MS,including reducing body weight gain and fat accumulation,improving glucose and lipid metabolism,and mitigating intestinal barrier damage,were attributed to the gut microbiota and could be replicated by FMT.16S r RNA sequencing analysis suggested that FMT from donor mice supplemented with VA and RA could regulate the gut microbiota composition.Particularly,FMT from RA supplemented mice displayed the potential to restore the diversity of gut microbiota and the ratio of Firmicutes to Bacteroidetes.Meanwhile,FMT from VA supplemented mice appeared to exert its effects by selectively influencing specific gut microbiota,such as the genus Akkermansia.Furthermore,our analysis identified 10 common differential amplicon sequence variants(ASVs)among groups compared to HFD-HFD group.Notably,ASV_36450 was negatively associated with metabolic parameters,suggesting that Lactobacillus might be the potential bacteria in regulating MS.Overall,our study demonstrated that FMT from VA and RA supplemented mice could ameliorate MS induced by HFD in mice through regulating specific gut microbiota.
文摘Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.
基金Funding support was from the Novo Nordisk Foundation with the project's grant number NNFSA210073688.
文摘Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.
文摘Crohn’s disease(CD)is an idiopathic,chronic,and recurrent inflammatory condition of the gastrointestinal tract.Recent studies suggest a potential role of gut microbiota in CD,particularly dysbiosis—an imbalance in gut bacteria.While dysbiosis is consistently observed in CD,it remains uncertain whether it is a cause or a consequence of the disease.Given its association with CD,the therapeutic potential of fecal microbiota transplantation(FMT)has been explored.This review examines the role of gut microbiota in CD,evaluates the therapeutic potential of probiotics and FMT,and highlights current research findings and limitations.Key studies on the relationship between gut dysbiosis,probiotics,and FMT in CD were analyzed,with a focus on randomized trials,meta-analyses,and clinical observations.Dysbiosis is a consistent feature of CD,but its causative role remains unclear.Probiotics,prebiotics,and synbiotics have shown no efficacy in inducing or maintaining remission in CD.FMT shows potential as a therapeutic option for CD,but its efficacy remains inconsistent and inconclusive.The variability in outcomes,including diminished effects over time despite repeated FMT,underscores the need for larger,well-controlled trials.Only one randomized controlled trial(RCT)has compared FMT with sham transplantation,but the sample size was very small.Other studies are limited by factors such as small sample sizes,lack of control groups,short follow-up periods,and inconsistent methodologies,making it challenging to draw definitive conclusions.While gut dysbiosis likely plays a role in CD pathogenesis,its causative role remains uncertain.Current evidence does not support FMT as a reliable treatment for inducing or maintaining remission in CD,though it appears generally safe.Larger,standardized,RCTs are necessary to clarify the therapeutic role of FMT in CD management.
基金Supported by the Science and Engineering Research Board,No.EMR/2016/007033.
文摘BACKGROUND Simultaneous assessment of gut microbiota in stool and tissue samples is crucial for a better understanding of their role in Crohn’s disease(CD),yet most reports have focused on fecal microbiota alone.Additionally,gut microbiota may serve as a clinically useful diagnostic biomarker of CD although data on this is limited.AIM To evaluate gut microbiota in tissue and stool samples in patients with active CD to understand the structure and function compared to healthy controls(HC).We also assessed their utility as a diagnostic biomarker of CD.METHODS Adult patients with active CD and HC were prospectively recruited for this study.The clinical and investigation details were recorded.Rectal mucosal biopsy and stool samples were obtained to assess the bacterial population.DNA was extracted,the V3-V4 region of the 16S rRNA gene was amplified,and library preparation was done and sequenced on the Illumina MiSeq platform.The bacterial diversity,composition,dysbiosis,predicted function,and predictors of disease state were estimated using the QIIME 2 pipeline and R packages.RESULTS We recruited 66 patients with CD(age 39.7±11.1 years,65.2%males)and 69 HC.Comparison of tissue with fecal microbiota in active CD showed significant differences in composition and predicted function.Both tissue and fecal microbiota from active CD showed reduced microbial diversity and compositional differences compared to HC,and disease state was a key determinant of bacterial population.Differences(CD vs HC)were noted in the abundance of several predicted synthetic and degradation pathways in both tissue and stool bacteria.Tissue microbiota was a superior predictor of active CD than stool(area under receiver operating characteristic curve 0.8 vs 0.62).CONCLUSION Gut microbial characteristics revealed significant structural and functional differences between CD and HC in both tissue and stool.Tissue bacteria performed well as a microbial biomarker for clinical diagnosis of CD.
基金supported by the National Natural Science Foundation of China(No.82030016,No 82230011 and No.82200533).
文摘Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.
基金Supported by National Key R&D Program of China,No.2022YFC2304505 and No.2021YFC2301801the Beijing Municipal of Science and Technology Major Project,No.Z221100007422002+1 种基金the Capital Funds for Health Improvement and Research,No.CFH-2024-1-2181Beijing Igandan Foundation,No.iGandanF-1082023-GSH011.
文摘Chronic liver disease has become a global health crisis,with increasing incidence and mortality rates placing a substantial burden on healthcare systems worldwide.A key factor in the progression of chronic liver disease is intestinal microbiota dysbiosis,which influences liver function via the intricate liver-gut axis.This axis plays a central role in various physiological processes,and disruptions in microbial composition can exacerbate liver pathology.Fecal microbiota transplantation(FMT)has emerged as a promising therapeutic strategy,with the potential to restore the composition and metabolic functions of the intestinal microbiota.Supported by encouraging findings from clinical trials and animal studies,FMT has demonstrated therapeutic benefits,including improvements in clinical symptoms,objective indicators,and long-term prognosis.These benefits encompass reductions in hepatic lipid deposition and inflammation,mitigation of complications in advanced liver disease,promotion of hepatitis B e antigen seroconversion,and enhancement of cognitive function.Although clinical evidence remains preliminary,current data underscore the transformative potential of FMT in managing chronic liver diseases.Nonetheless,challenges persist,including the need for standardized procedures,variability among donors,potential risks,and concerns regarding long-term safety.This review provides a comprehensive evaluation of the current literature on the efficacy and safety of FMT,while exploring future research directions to expand its application in liver disease management.
基金National Natural Science Foundation of Joint Fund in China (U22A20376)。
文摘Objective To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation(FMT)in patients with type 2 diabetes mellitus(T2DM),and to preliminarily identify the traditional Chinese medicine(TCM)syndrome element characteristics of FMT in the treatment of T2DM.Methods Between March 25,2023 and September 30,2024,T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine.Participants received oral microbiota capsules as an adjunct to metformin therapy.Information obtained by four diagnostic methods of TCM,along with clinical and laboratory parameters,was collected before and after the intervention.Metagenomic sequencing was employed to analyze the gut microbiota,and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera.According to the post-treatment reduction in glycosylated hemoglobin(HbA1c),patients were categorized into a response(R)group and a non-response(NR)group.Treatment outcomes,safety indicators,gut microbiota changes,and TCM syndrome element features were compared between the two groups.Results A total of 53 T2DM patients were included in the final analysis,and 30 patients were assigned to R group and 23 to NR group.After treatment,the R group exhibited significant reductions in HbA1c,fasting plasma glucose(FPG),and 2-hour postprandial glucose(2hPG)(P<0.05 or P<0.01).The NR group also showed significant decreases in HbA1c and FPG levels P<0.01 or P<0.05.Compared with the NR group,after treatment,FPG level in the R group demonstrated significant reductions(P<0.01).As compared with before treatment,pancreatic islet function demonstrated enhancement in the R group,a significant increase in the 2-hour pastprandial C-peptide(2hC-P)levels in R group(P<0.05),whereas no marked change was observed in the NR group.Regarding body composition indicators,the R group showed significantly lower waist-hip ratio(WHR),visceral fat(VF),and subcutaneous fat(SF)levels compared with the NR group(P<0.01).After treatment,the NR group exhibited a significant elevation in aspartate aminotransferase(AST)levels(P<0.05).Other safety-related indicators fluctuated within normal reference ranges,and no other adverse events,such as diarrhea,fever,or nausea,were reported.Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota,remodeling its overall structure.At the phylum level,the abundance of p_Firmicutes decreased significantly(P<0.01),while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly(P<0.01).At the family level,among the 125 identified taxa,the abundances of f_Bacteroidaceae,f_Lactobacillaceae,and f_Sutterellaceae were significantly elevated,whereas six families,including f_Lachnospiraceae,f_Ruminococcaceae,and f_Coriobacteriaceae,were significantly decreased(all P<0.05).Among the 367 taxa at the genus level,the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella,and significantly decreased abundances in eight genera,including g_Faecalibacterium,g_Ruminococcus,g_Blautia,and g_Collinsella(all P<0.05).Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters,g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide(FC-P)and 2hC-P(P<0.05).HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger(P<0.05)and a significantly negative correlation with g_Bacteroides and g_Collinsella(P>0.05).Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness,phlegm,and Yang deficiency.Before treatment,statistically significant reductions in syndrome element scores were observed for dampness,Yang deficiency,spleen,phlegm,Qi deficiency,Qi stagnation,and Yin deficiency(P<0.01),as well as for heat and liver(P<0.05).The NR group was mainly featured with Qi deficiency and Yin deficiency.Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency(P<0.01),and for spleen,Qi stagnation,liver,and blood deficiency(P<0.05).In this group,the score changes for Yang deficiency,Yin deficiency,heat,and dampness were not statistically significant(P>0.05).Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM.Patients with T2DM presented with specific TCM syndrome element characteristics,notably dampness,phlegm,and Yang deficiency,represent a highly responsive population to FMT therapy.
基金Supported by The Public Donated Grant"Intestine Initiative"National Nature Science Foundation of China,No.81670495
文摘Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.
文摘AIM To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha was examined. RESULTS FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating proinflammatory factors such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. CONCLUSION FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.
文摘The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals.However,there are still no definitive microbial pathogens linked to the onset of IBD.The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients.The special alterations of gut microbiota associated with IBD remain to be evaluated.The microbial interactions and hostmicrobe immune interactions are still not clarified.Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy,few available strains and no standardized administration.Fecal microbiota transplantation(FMT)may restore intestinal microbial ho-meostasis,and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection.Additionally,synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD.However,FMT-related barriers,including the mechanism of restoring gut microbiota,standardized donor screening,fecal material preparation and administration,and long-term safety should be resolved.The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germfree/human flora-associated animals and chemostat gut models.
基金Supported by Partially supported by the grant"Intestine Initiative"
文摘Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.
基金Scientific Research Project of Jiangsu Provincial Health Commission,No.H2018082Huai'an Natural Science Research Project,No.HAB201926Scientific Research Project of Translational Medicine Innovation Team of Huai'an First People's Hospital,No.YZHT201905。
文摘BACKGROUND Emerging evidence has demonstrated that fecal microbiota transplantation(FMT)has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis(UC),although the mechanism of FMT is unclear.AIM To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota,through association analysis of gut microbiota with colon transcriptome in mice.METHODS Dextran sodium sulfate(DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage.Severity of colon inflammation was measured by body weight,disease activity index,colon length and histological score.Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing.The differentially expressed genes(DEGs)in the colon were obtained by transcriptome sequencing.The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.RESULTS Compared with the DSS group,the weight loss,colon length shortening and inflammation were significantly alleviated in the FMT group.The scores of disease activity index and colon histology decreased obviously after FMT.FMT restored the balance of gut microbiota,especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter.In the transcriptomic analysis,128 DEGs intersected after DSS treatment and FMT.Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation.In the DSS group,there was an increase in colonic T helper CD4^(+)and T cytotoxic CD8^(+)cells by flow cytometry.FMT selectively downregulated the ratio of colonic CD4^(+)and CD8^(+)T cells to maintain intestinal homeostasis.Furthermore,Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G,CCL8 and IDO1.CONCLUSION FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.
基金Supported by the National Natural Science Foundation of China,No.82270590.
文摘BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and fibrosis.AIM To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in CD.METHODS Intestinal tissue and MAT were collected from 12 patients with CD.Histological manifestations and protein expression levels were analyzed to determine lesion characteristics.Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice.The intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.RESULTS Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota structure.Fetal microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD symptoms.Notably,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and adipokines.Furthermore,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.CONCLUSION Gut microbiota play a critical role in the histopathology of CD.Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.
基金Supported by Shaanxi Province Natural Science Basic Research Program-General Project,No.2019JM-580 and No.2021SF-314Project of Shaanxi Administration of Traditional Chinese Medicine,No.2019-ZZ-JC010Shaanxi Provincial Hospital of Traditional Chinese Medicine,No.2018-04 and No.2021-07。
文摘With the development of microbiology and metabolomics,the relationship between the intestinal microbiome and intestinal diseases has been revealed.Fecal microbiota transplantation(FMT),as a new treatment method,can affect the course of many chronic diseases such as metabolic syndrome,malignant tumor,autoimmune disease and nervous system disease.Although the mechanism of action of FMT is now well understood,there is some controversy in metabolic diseases,so its clinical application may be limited.Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection,and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases.However,the initial results are varied,suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT.The success of FMT depends on the microbial diversity and composition of donor feces.Therefore,clinical trials may fail due to the selection of ineffective donors,and not to faulty indication selection for FMT.A new understanding is that FMT not only improves insulin sensitivity,but may also alter the natural course of type 1 diabetes by modulating autoimmunity.In this review,we focus on the main mechanisms and deficiencies of FMT,and explore the optimal design of FMT research,especially in the field of cardiometabolic diseases.
文摘To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).METHODSWe searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles.RESULTSA total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration.CONCLUSIONData on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.
基金supported by the Xinjiang Lop Nur Wild Camels National Reserve Comprehensive Scientific Research Projects by The Environmental Protection Agency of China (20100228)
文摘This study aimed to reveal the microbial diversity in the fecal samples of bactrian camels using the 16 S r RNA sequencing analysis on the Illumina Mi Seq platform. Three fecal samples were collected from two geographical regions in China. Operational taxonomic unit（OTU） clustering was performed by identifying an OTU at 97% sequence identity. The alpha and beta diversities were applied to estimate the differences in microbial diversity among the three fecal samples. Totally, 4409, 3151 and 4075 OTUs in the fecal samples were identified in the Lop Nor wild camel（Camelus ferus）, the domestic camel（C. bactrianus） and Dunhuang wild camel（C. ferus）, respectively. The majority of bactreria were affiliated with phylum Firmicutes and Bacteroidetes in the three samples. The wild camels had higher gastrointestinal tract microbial diversity than the domestic one, while the microbial composition of the Lop Nor wild camel shared higher similarity with domestic camel at the genus and family levels than that of the Dunhuang wild camel did. Our results may provide a theoretical basis for assessing their health conditions and may thus be useful for protecting the critically endangered species of C. ferus.
文摘BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.
基金the National Key Research and Development Program of China(2017YFD0500502)。
文摘Background:Diarrhea is a major cause of morbidity and mortality in young calves,resulting in considerable economic loss for dairy farms.To determine if some gut microbes might have resistance to dysbiotic process with calf diarrhea by dictating the microbial co-occurrence patterns from birth to post-weaning,we examined the dynamic development of the gut microbiota and diarrhea status using two animal trials,with the first trial having 14 Holstein dairy calves whose fecal samples were collected 18 times over 78 d from birth to 15 d post-weaning and the second trial having 43 Holstein dairy calves whose fecal samples were collected daily from 8 to 18 days of age corresponding to the first diarrhea peak of trial 1.Results:Metataxonomic analysis of the fecal microbiota showed that the development of gut microbiota had three age periods with birth and weaning as the separatrices.Two diarrhea peaks were observed during the transition of the three age periods.Fusobacteriaceae was identified as a diarrhea-associated taxon both in the early stage and during weaning,and Clostridium_sensu_stricto_1 was another increased genus among diarrheic calves in the early stage.In the neonatal calves,Prevotella_2(ASV4 and ASV26),Prevotella_9(ASV43),and Alloprevotella(ASV14)were negatively associated with Clostridium_sensu_stricto_1(ASV48),the keystone taxa of the diarrhea-phase module.During weaning,unclassified Muribaculaceae(ASV28 and ASV44),UBA1819(ASV151),Barnesiella(ASV497),and Ruminococcaceae_UCG-005(ASV254)were identified being associated with non-diarrheic status,and they aggregated in the non-diarrhea module of co-occurrence patterns wherein unclassified Muribaculaceae(ASV28)and Barnesiella(ASV497)had a direct negative relationship with the members of the diarrhea module.Conclusions:Taken together,our results suggest that the dynamic successions of calf gut microbiota and the interactions among some bacteria could influence calf diarrhea,and some species of Prevotella might be the core microbiota in both neonatal and weaning calves,while species of Muribaculaceae might be the core microbiota in weaning calves for preventing calf diarrhea.Some ASVs affiliated with Prevotella_2(ASV4 and ASV26),Prevotella_9(ASV43),Alloprevotella(AVS14),unclassified Muribaculaceae(ASV28 and ASV44),UBA1819(ASV151),Ruminococcaceae_UCG-005(ASV254),and Barnesiella(ASV497)might be proper probiotics for preventing calf diarrhea whereas Clostridium_sensu_stricto_1(ASV48)might be the biomarker for diarrhea risk in specific commercial farms.
