Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodolo...Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles.We aimed to estimate the impact of a reduction of dietary variation(dietary convergence)on faecal microbiota composition among individuals consuming a Western-type diet.Methods 18 healthy volunteers recruited in the region of Flanders(Belgium)were followed up for 21 days.Participants were allowed to consume their habitual diet during a baseline and follow-up period(7 and 8 days,respectively),intersected by a 6-day intervention during which dietary options were restricted to oat flakes,whole milk and still water.Faecal samples were collected on a daily basis.Quantitative microbiome profiles were constructed,combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting.Blood samples were taken at the beginning and end of each study week.Results While the intervention did not affect transit time(as assessed through the analysis of stool moisture),consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type.Microbial load and Faecalibacterium abundance decreased markedly.Despite dietary restrictions,no convergence of microbial communities(reduction of interindividual and intraindividual variation)was observed.The effect size(ES)of the intervention on genus-level microbiome community differentiation was estimated as 3.4%,but substantial interindividual variation was observed(1.67%–16.42%).Conclusion The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES,with notable individual exceptions.Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.展开更多
Background Metabolic dysfunction-associated steatotic liver disease(MASLD)is the leading cause of chronic liver disease globally,with rising prevalence linked to metabolic syndrome(MetS).Excessive liver fat accumulati...Background Metabolic dysfunction-associated steatotic liver disease(MASLD)is the leading cause of chronic liver disease globally,with rising prevalence linked to metabolic syndrome(MetS).Excessive liver fat accumulation(steatosis)worsens disease progression and MASLD prognosis.Moreover,gut microbiota dysbiosis might promote steatosis,accelerating the disease progression to severe stages.Identifying gut microbiota signatures specific to steatosis severity might improve its diagnosis and inform personalised interventions in MASLD.This study aimed to characterise associations between gut microbiota composition and hepatic steatosis severity in a cohort of patients with MASLD/MetS.Ultimately,we aimed to assess the potential for microbiota features to enhance the diagnosis of severe steatosis.Methods A cross-sectional cohort of 61 patients with MetS with extensive clinical history was recruited at different stages of MASLD.Transient elastography was used to evaluate liver fibrosis and steatosis severity.Participants’faecal microbiota were profiled using 16S rRNA gene sequencing.Statistical analyses first identified correlations between microbiota profiles and patients’phenotypes,while disentangling important confounders such as medication.Identified features were then used to build predictive models for diagnosing severe steatosis.Results High steatosis severity was distinctly associated with a higher prevalence of the inflammation-associated Bacteroides 2(Bact2)-enterotype,accompanied by a lower proportion of beneficial commensals(eg,Akkermansia)and a higher proportion of opportunistic bacteria(eg,Streptococcus).Patients harbouring a Bact2-enterotype reached severe steatosis at lower Fatty Liver Index(FLI)thresholds.Using Bact2-carrier status together with FLI in a predictive model significantly improved the classification of severe steatosis(accuracy 90%,receiver operating characteristics 96%)when compared with FLI alone.Conclusion Gut microbiota composition and dysbiosis(defined as Bact2-enterotype)are distinctly associated with steatosis severity in MASLD/MetS.Patient stratification by microbiota composition enhances the diagnostic classification of severe steatosis in MASLD,suggesting a potential for personalised interventions in patients with microbiota dysbiosis.展开更多
基金funded by CREA grant ZKC7861 of the KU Leuven.SV-S,GK,JFV-C,RYT and JS were funded by a(post)doctoral fellowship from Research Foundation Flanders(FWO-Vlaanderen)GF was funded by the ReALity Innovation Fund,a Research Initiative of the State of Rhineland-Palatinate,GermanyThe Raes Lab received funding from VIB,KU Leuven,the Rega Institute for Medical Research and Novo Nordisk(PRIMA project).
文摘Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles.We aimed to estimate the impact of a reduction of dietary variation(dietary convergence)on faecal microbiota composition among individuals consuming a Western-type diet.Methods 18 healthy volunteers recruited in the region of Flanders(Belgium)were followed up for 21 days.Participants were allowed to consume their habitual diet during a baseline and follow-up period(7 and 8 days,respectively),intersected by a 6-day intervention during which dietary options were restricted to oat flakes,whole milk and still water.Faecal samples were collected on a daily basis.Quantitative microbiome profiles were constructed,combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting.Blood samples were taken at the beginning and end of each study week.Results While the intervention did not affect transit time(as assessed through the analysis of stool moisture),consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type.Microbial load and Faecalibacterium abundance decreased markedly.Despite dietary restrictions,no convergence of microbial communities(reduction of interindividual and intraindividual variation)was observed.The effect size(ES)of the intervention on genus-level microbiome community differentiation was estimated as 3.4%,but substantial interindividual variation was observed(1.67%–16.42%).Conclusion The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES,with notable individual exceptions.Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.
基金funded by national funds through FCT-Portuguese Foundation for Science and Technology,under the scope of the Cardiovascular R&D Center-UnIC(UIDB/00051/2020 and UIDP/00051/2020)JC-L was supported by a travel grant fellowship from the Research Foundation Flanders(V465523N)SV-S is a principal investigator in the BMFTR Cluster4Future CurATime(CurATime project microbAIome,03ZU1202CB)funded by the Federal Ministry of Research,Technology and Space(BMFTR).
文摘Background Metabolic dysfunction-associated steatotic liver disease(MASLD)is the leading cause of chronic liver disease globally,with rising prevalence linked to metabolic syndrome(MetS).Excessive liver fat accumulation(steatosis)worsens disease progression and MASLD prognosis.Moreover,gut microbiota dysbiosis might promote steatosis,accelerating the disease progression to severe stages.Identifying gut microbiota signatures specific to steatosis severity might improve its diagnosis and inform personalised interventions in MASLD.This study aimed to characterise associations between gut microbiota composition and hepatic steatosis severity in a cohort of patients with MASLD/MetS.Ultimately,we aimed to assess the potential for microbiota features to enhance the diagnosis of severe steatosis.Methods A cross-sectional cohort of 61 patients with MetS with extensive clinical history was recruited at different stages of MASLD.Transient elastography was used to evaluate liver fibrosis and steatosis severity.Participants’faecal microbiota were profiled using 16S rRNA gene sequencing.Statistical analyses first identified correlations between microbiota profiles and patients’phenotypes,while disentangling important confounders such as medication.Identified features were then used to build predictive models for diagnosing severe steatosis.Results High steatosis severity was distinctly associated with a higher prevalence of the inflammation-associated Bacteroides 2(Bact2)-enterotype,accompanied by a lower proportion of beneficial commensals(eg,Akkermansia)and a higher proportion of opportunistic bacteria(eg,Streptococcus).Patients harbouring a Bact2-enterotype reached severe steatosis at lower Fatty Liver Index(FLI)thresholds.Using Bact2-carrier status together with FLI in a predictive model significantly improved the classification of severe steatosis(accuracy 90%,receiver operating characteristics 96%)when compared with FLI alone.Conclusion Gut microbiota composition and dysbiosis(defined as Bact2-enterotype)are distinctly associated with steatosis severity in MASLD/MetS.Patient stratification by microbiota composition enhances the diagnostic classification of severe steatosis in MASLD,suggesting a potential for personalised interventions in patients with microbiota dysbiosis.
