The Effect Inulin-type Fructans Supplement On Gut Microbiota: A Randomized Controlled Clinical Study

Background:Intestinal microflora disorder is related to the development of many metabolic diseases.Manipulating intestinal flora is an important strategy for prevention and treatment of metabolic diseases.Prebiotics intervention is one of the effective ways to modulate intestinal microbiota.Prebiotics is a kind of non-digestible dietary fiber,which can specific stimulate probiotics growth,such as Bifidobacterium and Lactobacillus,producing short chain fatty acids and other beneficial substances,thereby promoting human health.Studies have shown that prebiotics not only play a proliferation effect on Bifidobacteria and Lactobacillus,but may also affect the whole intestinal microecology.Previous studies about prebiotics on intestinal microflora are mostly based on non-sequencing technology.Few prebiotics have been applied to the study the human intestinal microecosystem impact using high-throughput sequencing.Objectives:1.To investigate the effects of FOS and inulin on glucose parameters,lipid profile,uric acid,homocysteine,C-reactive protein,gut microbiota structure and function in Chinese healthy populations;2.To compare the effects of different source of inulin-type fructans on intestinal flora and clinical parameters;3.To establish machine learning models based on initial gut microbiota for predicting the variation of glucose metabolism,uric acid and other blood parameters after prebiotic intake,which might provide a guidance to personalized diet strategy.Methods:A randomized double-blind placebo-controlled study was conducted with 135 healthy adults with FOS and inulin supplement for 4 weeks(15g/d).Blood samples were taken before and after the intervention,fecal sampling were performed at the beginning,midterm and the end of the study.Oral glucose tolerance test and anthropometry were performed before and after intervention.16S rDNA microbiota profiling was applied to assess the composition and function of gut microbiota.Machine learning models base on initial gut microbiota data were used to establish the prediction model about blood parameters.Results:Four weeks intake of FOS and inulin,but not placebo,markedly increased abundance of Bifidobacterium with significant effects on overall microbial richness and diversity.Meanwhile,the manipulation of FOS and inulin on gut microbiota was also manifested in the decreased abundance of Roseburia,Phascolarctobacterium,Ruminococcus,Holdemania and Lachnospiraceae.We did not observe any differences in host anthropometric,lipid metabolism,blood glucose metabolism,nor insulin sensitivity after ITF intake.At the same time,we did not find any different effect between inulin and FOS consumption.In addition,using the baseline data of gut microbiota,the random forest model successfully classified the increased-responders and decreased-responders in OGTT,UA and HCY.The AUC of receiver operating characteristic(ROC)curve was 0.71,0.71 and 0.75,respectively.Further,we built an index to successfully predict the response of OGTT after FOS and inulin intervention.In the training model,index was positively correlated with glucose tolerance(r=0.41,p<0.01).In the validation model,index was positively correlated with glucose tolerance(r=0.39,p<0.05).Conclusions:Four-week supplementation of FOS and inulin indeed led to ecosystem-wide microbiota shifts,and this shifts had showed stably after 2 week,but this did not produce significant alteration in host lipid and glucose metabolism and uric acid,homocysteine,C-reactive protein.ITF from different source show similar effects on gut microbiota and clinical parameters.With the data of initial gut microbiome,machine-learning classification algorithm identified the increased-responders and decreased-responders on OGTT,UA and HCY.We could use this algorithm to predict the individualized response of OGTT after prebiotics intervention,which was potentially of practical value to nutritional strategy.