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
The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbio...The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.展开更多
Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies w...Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.展开更多
Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substan...Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.展开更多
In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT...In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT)for irritable bowel syndrome(IBS),the factors which affect the outcomes of FMT in IBS patients,and challenges.FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS.The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials,yielding divergent outcomes.The current frontier in this field seeks to elucidate these variations,underscore the existing knowledge gaps that necessitate exploration,and provide a guideline for successful FMT implementation in IBS patients.At the same time,the application of FMT as a treatment for IBS confronts several challenges.展开更多
Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug h...Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.展开更多
As we are facing an aging society,anti-aging strategies have been pursued to reduce the negative impacts of aging and increase the health span of human beings.Gut microbiota has become a key factor in the anti-aging p...As we are facing an aging society,anti-aging strategies have been pursued to reduce the negative impacts of aging and increase the health span of human beings.Gut microbiota has become a key factor in the anti-aging process.Modulation of gut microbiota by fecal microbiota transplantation(FMT)to prevent frailty and unhealthy aging has been a hot topic of research.This narrative review summarizes the benefits of FMT for health span and lifespan,brains,eyes,productive systems,bones,and others.The mechanisms of FMT in improving healthy aging are discussed.The increased beneficial bacteria and decreased pathological bacteria decreased gut permeability and systemic inflammation,increased short-chain fatty acid(SCFA)and SCFA-producing bacteria,and other factors are listed as mechanisms of FMT to improve healthy aging.The points that need to be considered to ensure the optimal outcomes of FMT are also discussed,such as recipients’age,sex,genetic background,and gut microbiota after FMT.Although thisfield is still in its infancy,it has shown that FMT has great potential to improve healthy aging.展开更多
BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation(FMT)as a therapy for ulcerative colitis(UC).However,the treatment processes and outcomes of these studies vary.AIM ...BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation(FMT)as a therapy for ulcerative colitis(UC).However,the treatment processes and outcomes of these studies vary.AIM To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis.METHODS The inclusion criteria involved reports of adult patients with UC treated with FMT,while studies that did not report clinical outcomes or that included patients with infection were excluded.Clinical remission(CR)and endoscopic remission(ER)were the primary and secondary outcomes,respectively.RESULTS We included nine studies retrieved from five electronic databases.The FMT group had better CR than the control group[relative risk(RR)=1.53;95%confidence interval(CI):1.19-1.94;P<0.0008].ER was statistically significantly different between the two groups(RR=2.80;95%CI:1.93-4.05;P<0.00001).Adverse events did not differ significantly between the two groups.CONCLUSION FMT demonstrates favorable performance and safety;however,well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended.Furthermore,standardizing the FMT process is urgently needed for improved safety and efficacy.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 Metabolic syndrome is a multifactorial disease,and the gut microbiota may play a role in its pathogenesis.Obesity,especially abdominal obesity,is associated with insulin resistance,often increasing the risk...BACKGROUND Metabolic syndrome is a multifactorial disease,and the gut microbiota may play a role in its pathogenesis.Obesity,especially abdominal obesity,is associated with insulin resistance,often increasing the risk of type two diabetes mellitus,vascular endothelial dysfunction,an abnormal lipid profile,hypertension,and vascular inflammation,all of which promote the development of atherosclerotic cardiovascular disease.AIM To evaluate the outcomes of fecal microbiota transplantation(FMT)in patients with metabolic syndrome.METHODS This was a randomized,single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome.We selected 32 female patients,who were divided into eight groups of four patients each.All of the patients were submitted to upper gastrointestinal endoscopy.In each group,two patients were randomly allocated to undergo FMT,and the other two patients received saline infusion.The patients were followed for one year after the procedures,during which time anthropometric,bioimpedance,and biochemical data were collected.The patients also had periodic consultations with a nutritionist and an endocrinologist.The primary end point was a change in the gut microbiota.RESULTS There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure.However,we found no difference between the two groups in terms of the clinical parameters evaluated.CONCLUSION There were no significant differences in biochemical or anthropometric parameters,between the two groups evaluated.Nevertheless,there were significant postprocedural differences in the microbiota composition between the placebo group.To date,clinical outcomes related to FMT remain uncertain.展开更多
Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatt...Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatty liver hemorrhagic syndrome(FLHS)in laying hens and the underlying mechanisms remain to be elucidated.Here,we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet(HFD)-induced FLHS laying hen model by decreasing the levels of TG,TC,ALT and ALP.The lipid accumulation and pathological score of liver were also relieved after GBE treatment.Moreover,GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH,SOD,T-AOC,GSH-PX and reducing MDA,and downregulated the expression of genes related to lipid synthesis(FAS,LXRα,GPAT1,PPARγand Ch REBP1)and inflammatory cytokines(TNF-α,IL-6,TLR4 and NF-κB)in the liver.Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota,particularly elevated the abundance of Megasphaera in the cecum.Meanwhile,targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs,acetate and propionate,which were positively correlated with the GBE-enriched gut microbiota.Finally,we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation(FMT).Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota.Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
BACKGROUND Fecal microbiota transplantation(FMT)has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis(UC).FMT modulates the Toll-like receptor 4(TLR4)signaling ...BACKGROUND Fecal microbiota transplantation(FMT)has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis(UC).FMT modulates the Toll-like receptor 4(TLR4)signaling pathway to treat some other diseases.However,it remains unknown whether this modulation is also involved in the treatment of UC.AIM To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate(DSS)-induced mice and explain the mechanism of FMT on UC,through association analysis of gut microbiota with colon transcriptome in mice.METHODS A mouse colitis model was constructed with wild-type(WT)and TLR4-knockout(KO)mice.Fecal microbiota was transplanted by gavage.Colon inflammation severity was measured by disease activity index(DAI)scoring and hematoxylin and eosin staining.Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing.Gene expression in the mouse colon was obtained by transcriptome sequencing.RESULTS The KO(DSS+Water)and KO(DSS+FMT)groups displayed indistinguishable body weight loss,colon length,DAI score,and histology score,which showed that FMT could not inhibit the disease in KO mice.In mice treated with FMT,the relative abundance of Akkermansia decreased,and Lactobacillus became dominant.In particular,compared with those in WT mice,the scores of DAI and colon histology were clearly decreased in the KO-DSS group.Microbiota structure showed a significant difference between KO and WT mice.Akkermansia were the dominant genus in healthy KO mice.The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia.Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus.The top nine genes correlating with Akkermansia included Aqp4,Clca4a,Dpm3,Fau,Mcrip1,Meis3,Nupr1 L,Pank3,and Rps13(|R|>0.9,P<0.01).CONCLUSION FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway.TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment.Akkermansia bear great therapeutic potential for colitis.展开更多
Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbio...Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbiota contribute to im-mune system development,energy homeostasis and digestion.Exo-and endoge-nous factors can alter its composition.Disturbance of microbiota,also known as dysbiosis,is associated with various pathological conditions.Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool.GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections.Ad-ditionally,it can influence response to treatments,including those for cancers,by altering drug bioavailability.A thorough understanding of its function has per-mitted significant development in therapeutics,such as probiotics and fecal trans-plantation.Hence,GM should be considered as a ground-breaking biological parameter,and it is advisable to be investigated and reported in literature in a more consistent and systematic way.展开更多
Clostridioides difficile infection(CDI)is a global health problem.The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures,but there are still contradictions.In a retr...Clostridioides difficile infection(CDI)is a global health problem.The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures,but there are still contradictions.In a retrospective study entitled“Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes”published in World J Gastrointest Surg 2021,the author found that prior appendectomy affects the severity of CDI.Appendectomy may be a risk factor for increasing the severity of CDI.Therefore,it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.展开更多
Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly ...Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.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
BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transpl...BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical phenomena.However,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been reported.AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.METHODS We conducted a prospective,open-label,single-center clinical study.Eleven CD patients underwent WMT.Their clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the procedure.RESULTS Seven of the 11 patients(63.6%)showed an optimal clinical response three months post-WMT.Gut microbiome diversity significantly increased after WMT,consistent with improved clinical symptoms.Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia coli.In addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors.However,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after WMT.CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s microbiome.Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.展开更多
Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality o...Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality of life;therefore,safe and effective therapy with long-term benefits is urgently needed.Microbiota treatment has potential value for FC treatment.Microbiota treatments include modulators such as probiotics,prebiotics,synbiotics,postbiotics,and fecal micro-biota transplantation(FMT).Some probiotics and prebiotics have been adopted,and the efficacy of other microbiota modulators is being explored.FMT is con-sidered an emerging field because of its curative effects;nevertheless,substantial work must be performed before clinical implementation.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
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the National Natural Science Foundation of China,No.82104525the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.21KJB360009Health Commission of Zhejiang Province Scientific Research Foundation,No.2024KY247.
文摘The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.
文摘Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.
基金supported by the National Natural Science Foundation of China(32001652)Chinese Universities Scientific Fund(2452018062)Keypoint Research and Invention Program of Shannxi Province(2021ZDLNY05-06)。
文摘Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.
文摘In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT)for irritable bowel syndrome(IBS),the factors which affect the outcomes of FMT in IBS patients,and challenges.FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS.The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials,yielding divergent outcomes.The current frontier in this field seeks to elucidate these variations,underscore the existing knowledge gaps that necessitate exploration,and provide a guideline for successful FMT implementation in IBS patients.At the same time,the application of FMT as a treatment for IBS confronts several challenges.
基金Supported by The Science and Technology Plan of Liaoning Province,China,No.2022JH2/101500063.
文摘Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.
基金This work was sponsored by Natural Science Foundation of Chongqing,China(cstc2021jcyjbshX0176 to Ting Gong)National Natural Science Foundation of China(81900980 to Huifen Ding).
文摘As we are facing an aging society,anti-aging strategies have been pursued to reduce the negative impacts of aging and increase the health span of human beings.Gut microbiota has become a key factor in the anti-aging process.Modulation of gut microbiota by fecal microbiota transplantation(FMT)to prevent frailty and unhealthy aging has been a hot topic of research.This narrative review summarizes the benefits of FMT for health span and lifespan,brains,eyes,productive systems,bones,and others.The mechanisms of FMT in improving healthy aging are discussed.The increased beneficial bacteria and decreased pathological bacteria decreased gut permeability and systemic inflammation,increased short-chain fatty acid(SCFA)and SCFA-producing bacteria,and other factors are listed as mechanisms of FMT to improve healthy aging.The points that need to be considered to ensure the optimal outcomes of FMT are also discussed,such as recipients’age,sex,genetic background,and gut microbiota after FMT.Although thisfield is still in its infancy,it has shown that FMT has great potential to improve healthy aging.
基金the Tianjin Health Science and Technology Project,No.TJWJ2021MS011.
文摘BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation(FMT)as a therapy for ulcerative colitis(UC).However,the treatment processes and outcomes of these studies vary.AIM To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis.METHODS The inclusion criteria involved reports of adult patients with UC treated with FMT,while studies that did not report clinical outcomes or that included patients with infection were excluded.Clinical remission(CR)and endoscopic remission(ER)were the primary and secondary outcomes,respectively.RESULTS We included nine studies retrieved from five electronic databases.The FMT group had better CR than the control group[relative risk(RR)=1.53;95%confidence interval(CI):1.19-1.94;P<0.0008].ER was statistically significantly different between the two groups(RR=2.80;95%CI:1.93-4.05;P<0.00001).Adverse events did not differ significantly between the two groups.CONCLUSION FMT demonstrates favorable performance and safety;however,well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended.Furthermore,standardizing the FMT process is urgently needed for improved safety and efficacy.
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.
文摘BACKGROUND Metabolic syndrome is a multifactorial disease,and the gut microbiota may play a role in its pathogenesis.Obesity,especially abdominal obesity,is associated with insulin resistance,often increasing the risk of type two diabetes mellitus,vascular endothelial dysfunction,an abnormal lipid profile,hypertension,and vascular inflammation,all of which promote the development of atherosclerotic cardiovascular disease.AIM To evaluate the outcomes of fecal microbiota transplantation(FMT)in patients with metabolic syndrome.METHODS This was a randomized,single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome.We selected 32 female patients,who were divided into eight groups of four patients each.All of the patients were submitted to upper gastrointestinal endoscopy.In each group,two patients were randomly allocated to undergo FMT,and the other two patients received saline infusion.The patients were followed for one year after the procedures,during which time anthropometric,bioimpedance,and biochemical data were collected.The patients also had periodic consultations with a nutritionist and an endocrinologist.The primary end point was a change in the gut microbiota.RESULTS There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure.However,we found no difference between the two groups in terms of the clinical parameters evaluated.CONCLUSION There were no significant differences in biochemical or anthropometric parameters,between the two groups evaluated.Nevertheless,there were significant postprocedural differences in the microbiota composition between the placebo group.To date,clinical outcomes related to FMT remain uncertain.
基金funded by the National Key Research and Development Program of China(2022YFA1304201)the Beijing Natural Science Foundation(6222032)+2 种基金the Starting Grants Program for Young Talents at China Agricultural Universitythe 2115 Talent Development Program of China Agricultural UniversityChinese Universities Scientific Fund。
文摘Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatty liver hemorrhagic syndrome(FLHS)in laying hens and the underlying mechanisms remain to be elucidated.Here,we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet(HFD)-induced FLHS laying hen model by decreasing the levels of TG,TC,ALT and ALP.The lipid accumulation and pathological score of liver were also relieved after GBE treatment.Moreover,GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH,SOD,T-AOC,GSH-PX and reducing MDA,and downregulated the expression of genes related to lipid synthesis(FAS,LXRα,GPAT1,PPARγand Ch REBP1)and inflammatory cytokines(TNF-α,IL-6,TLR4 and NF-κB)in the liver.Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota,particularly elevated the abundance of Megasphaera in the cecum.Meanwhile,targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs,acetate and propionate,which were positively correlated with the GBE-enriched gut microbiota.Finally,we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation(FMT).Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota.Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
基金the Scientific Research Project of Jiangsu Provincial Health Commission,No.H2018082Huai’an Natural Science Research Project Project,No.HAB201926Scientific Research Project of Translational Medicine Innovation Team of Huai’an First People’s Hospital,No.YZHT201905.
文摘BACKGROUND Fecal microbiota transplantation(FMT)has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis(UC).FMT modulates the Toll-like receptor 4(TLR4)signaling pathway to treat some other diseases.However,it remains unknown whether this modulation is also involved in the treatment of UC.AIM To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate(DSS)-induced mice and explain the mechanism of FMT on UC,through association analysis of gut microbiota with colon transcriptome in mice.METHODS A mouse colitis model was constructed with wild-type(WT)and TLR4-knockout(KO)mice.Fecal microbiota was transplanted by gavage.Colon inflammation severity was measured by disease activity index(DAI)scoring and hematoxylin and eosin staining.Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing.Gene expression in the mouse colon was obtained by transcriptome sequencing.RESULTS The KO(DSS+Water)and KO(DSS+FMT)groups displayed indistinguishable body weight loss,colon length,DAI score,and histology score,which showed that FMT could not inhibit the disease in KO mice.In mice treated with FMT,the relative abundance of Akkermansia decreased,and Lactobacillus became dominant.In particular,compared with those in WT mice,the scores of DAI and colon histology were clearly decreased in the KO-DSS group.Microbiota structure showed a significant difference between KO and WT mice.Akkermansia were the dominant genus in healthy KO mice.The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia.Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus.The top nine genes correlating with Akkermansia included Aqp4,Clca4a,Dpm3,Fau,Mcrip1,Meis3,Nupr1 L,Pank3,and Rps13(|R|>0.9,P<0.01).CONCLUSION FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway.TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment.Akkermansia bear great therapeutic potential for colitis.
文摘Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbiota contribute to im-mune system development,energy homeostasis and digestion.Exo-and endoge-nous factors can alter its composition.Disturbance of microbiota,also known as dysbiosis,is associated with various pathological conditions.Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool.GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections.Ad-ditionally,it can influence response to treatments,including those for cancers,by altering drug bioavailability.A thorough understanding of its function has per-mitted significant development in therapeutics,such as probiotics and fecal trans-plantation.Hence,GM should be considered as a ground-breaking biological parameter,and it is advisable to be investigated and reported in literature in a more consistent and systematic way.
文摘Clostridioides difficile infection(CDI)is a global health problem.The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures,but there are still contradictions.In a retrospective study entitled“Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes”published in World J Gastrointest Surg 2021,the author found that prior appendectomy affects the severity of CDI.Appendectomy may be a risk factor for increasing the severity of CDI.Therefore,it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.
文摘Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
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 Innovation Platform for Academicians of Hainan Province,No.YSPTZX202313Hainan Province Clinical Medical Center,No.2021818+3 种基金Hainan Provincial Health Industry Research Project,No.22A200078Hainan Provincial Postgraduate Innovation Research Project,No.Qhyb2022-133Hainan Medical University Graduate Student Innovative Research Project,No.HYYB2022A18Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine,No.2020-3HIM.
文摘BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical phenomena.However,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been reported.AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.METHODS We conducted a prospective,open-label,single-center clinical study.Eleven CD patients underwent WMT.Their clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the procedure.RESULTS Seven of the 11 patients(63.6%)showed an optimal clinical response three months post-WMT.Gut microbiome diversity significantly increased after WMT,consistent with improved clinical symptoms.Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia coli.In addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors.However,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after WMT.CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s microbiome.Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.
基金Supported by the Project of the National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,No.NCRCGPLAGH-2023005.
文摘Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality of life;therefore,safe and effective therapy with long-term benefits is urgently needed.Microbiota treatment has potential value for FC treatment.Microbiota treatments include modulators such as probiotics,prebiotics,synbiotics,postbiotics,and fecal micro-biota transplantation(FMT).Some probiotics and prebiotics have been adopted,and the efficacy of other microbiota modulators is being explored.FMT is con-sidered an emerging field because of its curative effects;nevertheless,substantial work must be performed before clinical implementation.
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.