Research Paper Volume 12, Issue 10 pp 9173—9187

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

Yawen Zhang1,2, *, , Luyi Chen1,2, *, , Mengjia Hu1,2, *, , John J. Kim3, , Renbin Lin1,2, , Jilei Xu1,2, , Lina Fan1,2, , Yadong Qi1,2, , Lan Wang1,2, , Weili Liu1,2, , Yanyong Deng1, , Jianmin Si1,2, , Shujie Chen1,2, ,

  • 1 Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
  • 2 Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
  • 3 Division of Gastroenterology, Loma Linda University Health, Loma Linda, CA 92354, USA
* Equal contribution

Received: November 11, 2019       Accepted: April 17, 2020       Published: May 25, 2020
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


RS2: Type 2 resistant starch; HF: high-fat; HFRS: high-fat+20%RS2; MUC2: mucin2; RS: Resistant starch; SCFA: short chain fatty acid; NAFLD: non-alcoholic fatty acid disease; LPS: lipopolysaccharide; IL-2: interleukin-2; IL-4: interleukin-4; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1 β; COGs: clusters of orthologous groups; FER: food efficiency ratio; PBS: phosphate-buffered saline; H&E: hematoxylin and eosin; NAS: NAFLD activity score; PAS-AB: Periodic acid-Schiff-alcian blue; OTUs: operational taxonomic units; RDP: Ribosomal Database Project; QIIME: Quantitative Insights Into Microbial Ecology; PICRUSt: Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.