Dietary type 2 resistant starch improves systemic inflammation and intestinal permeability by modulating microbiota and metabolites in aged mice on high-fat diet

Yawen Zhang,Renbin Lin,John J Kim,Yadong Qi,Yanyong Deng,Luyi Chen,Lina Fan,Shujie Chen,Jianmin Si,Lan Wang,Weili Liu,Jilei Xu,Mengjia Hu

doi:10.18632/aging.103187

Yawen Zhang, Renbin Lin + Show 11 more

Open Access

https://doi.org/10.18632/aging.103187

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Abstract

Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged mice on high-fat diet. In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged mice on high-fat diet mediated by changes in gut microbiome and metabolites.

Highlights

Popularization of western dietary habits has led to higher consumption of energy-dense food, rich in fat, world-wide [1]
In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% Type 2 resistant starch (RS2) (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet
Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella

Summary

Introduction

Popularization of western dietary habits has led to higher consumption of energy-dense food, rich in fat, world-wide [1]. Consumption of high-fat diet is associated with aging and disease processes including metabolic syndrome, cardiovascular disease, and colon cancer [2,3,4]. There is growing interest in interventions aiming at prevention of ill-effects of high-fat diet in the middle-aged and elderly population. Resistant starch (RS), a type of dietary fiber, has been extensively studied for the past few decades conferring broad range of health benefits including improvement in www.aging-us.com glycemic control, weight loss in obesity, and reduction in the risk of colon cancer [9]. Recent studies demonstrated that RS2 may improve host responses and brain functions in aged animals [12,13,14]. Whether RS2 can improve host health in middle-aged and elderly population on high-fat diet is unclear and the underlying mechanism is largely unknown

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