Effect Of Dietary Fiber On Obese People Based On Full Transcriptome Sequencing And Gut Microbiota

Objective: To evaluate the diagnostic value of different obesity indicators for extra body fat,to analysis obesity-related risk factors in behavior and diet,to investigate the effect of dietary fiber on gut microbiota,non-coding RNA and mRNA in obese individuals.To provide theoretical basis for the establishment of dietary fiber as a core element of the intervention that ultimately reduce the prevalence of obesity.Methods: 1)Questionnaire survey,physical examination,body composition measurement,blood test and diet survey were conducted among all the participants.We investigated the BMI,waist circumference,waist-to-height ratio,TMI,CMI,VAI,LAP,ABSI,BRI and other obesity indicators,behavior and diet of participants.We also used Lasso-Logistic regression to screen risk factors of obesity;2)We conducted a 5-days dietary fiber intervention study on thirty obese subjects obtained from epidemiological investigations,and collected fecal specimens from all of them before and after the intervention,detected changes on the gut microbiota of the subjects before and after the intervention.3)Another six obese subjects were also recruited for a 5-days dietary fiber intervention;Blood samples were collected before and after intervention to evaluated the changes on non-coding RNA and mRNA expression.The effect of dietary fiber on C2 expression was analyzed by measuring mRNA C2 level in blood samples before and after dietary fiber intervention among 30 subjects who were recruited in the second part of the intervention study.Results: 1.3287 subjects were included in the epidemiological survey.1)Among them 88.77%were obesity based on body fat percentage,32.55% were obesity based on body mass index,55.55% were obesity based on waist circumference,and 75.72% were obesity based on waist-to-height;2)The linear correlation between TMI,CMI,VAI,LAP,ABSI,BRI and body fat percentage showed that TMI and body fat percentage were best correlated regardless of gender.When evaluated the diagnostic value of different obesity indicators for extra body fat percentage,we found that TMI,LAP,and BRI have a better diagnostic value for exceeding body fat percentage.The AUCs and their 95% CI were 0.843（0.821⁰.866）,0.811（0.787⁰.834）and 0.852（0.831⁰.874）respectively;3)When establishing regression models based on different obesity indicators,we found smoking and work styles were associated with obesity.There also was a correlation between the intake frequency some types food and obesity.2.1)The 5-days dietary fiber intervention in this study did not cause changes in the diversity of gut microbiota;2)At the family level,Porphyromonadaceae and Propionibacteriaceae significantly increased after the intervention,dietary fiber promoted the growth of these two bacteria.At the genus level,12 types of bacteria were significant different before and after intervention.Sneathia,Pediococcus,Anaerofustis increased,while Odoribacter,Weissella,Enterobacter,Okibacterium,Anoxybacillus,Aerococcus decreased;At species level,32 species of bacteria were significant different before and after the intervention,of which 7 species decreased and 25 species increased after intervention;3)At phylum level,the number of Firmicutes decreased after the intervention,while the number of Bacteroidetes increased after the intervention,so the ratio of Firmicutes/Bacteroidete was decreased;At genus level,the number of beneficial bacteria Parabacteroides significant increased after intervention,and Parabacteroides_distasonis_ATCC₈503 increased after intervention.3.1)Full-transcriptome sequencing of RNA in blood samples showed that 5-days dietary fiber intervention had a significant effect on a variety of mRNAs and ncRNAs.The mRNAs affected by dietary fiber intervention in this study were SOGA1,ONECUT2,SIK1,ISX,and GIP.The gene functions involved in differential mRNA were increasing insulin sensitivity,regulating intestinal barrier function,maintaining blood glucose stability.2)The intervention caused 97 differentially expressed mRNAs,377 differentially expressed lncRNAs,86 differentially expressed circRNAs,13 differentially expressed known miRNAs,37 differentially expressed novel miRNAs,and formed 4 groups of lncRNA-miRNA-mRNA regulatory networks and 3 groups of circRNA-miRNA-mRNA,these two types of regulatory networks involved 2 target mRNAs: C2 and RAET1 E.3)Dietary fiber intervention can significantly down-regulate C2 expression.Conclusions: 1)There was a good correlation between BRI and BF%,it can be used as a substitute index for screening exceeding body fat percentage in epidemiological survey;2)Dietary fiber did not change the diversity of the gut microbiota,but can selectively change some bacteria at the family and genus level,promote the growth of beneficial bacteria,and inhibit the growth of harmful bacteria.The ratio of gut microbiota Firmicutes/Bacteroidetes decreased after intervention,suggesting that Firmicutes/Bacteroidetes may be the target bacteria of dietary fiber;At genus level,the number of beneficial bacteria Parabacteroides significant increased after intervention,and studies have confirmed that Parabacteroides_distasonis is a new type of probiotics;3)The gene functions of differential mRNA mainly involved increasing insulin sensitivity,regulating intestinal barrier function,maintaining blood glucose stability.Dietary fiber intervention can significantly down-regulate the expression of C2,which is one of the upstream genes in the complement family.The main physiological processes involved in the complement family are infection and inflammation.Down-regulation of C2 expression by dietary fiber suggests that dietary fiber can improve the inflammatory response in obese individuals then reverse or control the progress of obesity.