| Dysbiosis of the gut microbiota is not only the result of metabolic diseases such as obesity and type 2 diabetes but also is an important driving force for disease development.It is one of the effective ways to improve human health via manipulating gut microbiota with dietary intervention.In order to identify the relationship between gut microbiota and human health,and to realize the precise nutrition intervention,it is necessary to analyze the gut microbiome at strain level,which results from the fact that the bacterial function is strain-specific.In this study,based on clinical dietary intervention trials,we developed a metagenomic analyzing strategy,which adopted ecological theory and combined metabolic data,to explore how high fibre diet improve the health of obese children and type 2 diabetes adults via modulating gut microbiome,to find the potential gut microbial members having close relationship with the development of disease and to disclose the potential mechanisms.We found that the Prader-Willi syndrome(PWS)and simple obese(SO)children had similar gut microbial structure and function before the intervention.After receiving the dietary intervention with a diet rich in non-digestible carbohydrate,both cohorts got significant body weight loss and improvement of lipid homeostasis and inflammation etc.Meanwhile,their gut microbiome were changed significantly and the two groups showed similar changes.Among the 118 high-quality bacterial draft genomes,we found 22 genomes,which not only had correlations with indoxyl sulfate or trimethylamine N-oxide,but also had the genes involved in the production of their precursors.In addition,by performing co-abundance network and functional guild analysis,we obtained 18 guilds and identified the Bifidobacterium pseudocatenulatum-dominating one,which might play decisive roles in defining gut microbial structure and had significant correlation with improved human health.Five B.pseudocatenulatum strains were isolated from one post-intervention sample of a PWS child.Based on the whole genomes of the 5 strains and the metagenomes of this child,we found that the 5 strains showed differential responses during the intervention and strain-specific correlations with host health.Comparative genomics showed that genomic microdiversity,including the different copy numbers of core functional genes,might have contributed to these differences.When exploring the effects of diet on gut resistome,we found that both the richness and diversity of the gut resistome of the obese child were reduced after the intervention.We constructed the distribution network,which linked the antibiotic resistant genes with their carriers,and found that the carriers belonged to Klebsiella,Enterobacter and Escherichia were the hubs for multiple antibiotic resistances.They were reduced after the intervention.In addition,we found that the high dietary fibre diet also played a beneficial role in the healthy improvement of type 2 diabetes patients.The changes of gut microbiome were significantly correlated with the improved health in type 2 diabetes patients.We found that the short-chain fatty acid(SCFAs),which were produced by gut microbiota via utilizing dietary fibre,were the key bacterial metabolites for alleviating the type 2 diabetes mellitus phenotype.Despite the fact that 141/154 high quality draft genomes had the genetic capability to produce SCFAs,only 15 were enriched after the intervention,which were supposed to be active SCFAs producers.When the active SCFAs producers had greater diversity and total abundance,participants had better improvement in HbA1 c.Taken together,the metagenomic analyzing strategy established in this study can effectively analyze the changes of gut microbiome at strain/genome level.When adopting ecological theory and combing other omics data,it can systematically identify key gut microbiota having influence on human health,which might be a strategy applied in the disease studies and promote the gut microbiome application in clinical diagnosis and treatment. |
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