Research Paper Volume 12, Issue 17 pp 17480—17502
Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus
- 1 School of Traditional Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 2 Department of Emergency Medicine, Zhongshan Hospital, Dalian University, Dalian 116001, China
Received: February 25, 2020 Accepted: July 6, 2020 Published: September 12, 2020
https://doi.org/10.18632/aging.103756How to Cite
Abstract
Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.
Abbreviations
T2DM: type 2 diabetes mellitus; IR: insulin resistance; LP: leptin resistance; ZDF rats: Zucker Diabetic Fatty rats; FMT: fecal microbiota transplantation; OGTT: Oral Glucose Tolerance Test; ITT: Insulin Tolerance Test; OTU: Operational Taxonomic Units; PCoA: UniFrac principal coordinates analysis; PLS-DA: partial least squares discriminant analysis; KEGG: KEGG Pathway Database; COG: Cluster of Orthologous Groups of Proteins; Rfam: RNA families; PICRUSt: Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; GC-TOFMS: time-of-flight mass spectrometry system; OPLS-DA: Orthogonal Partial Least Squares Discriminant Analysis; JAK2: Janus Kinase Signal Transducers 2; IRS2: Insulin Receptor Substrate 2; Akt: Protein Kinase B; FOXO1: Forkhead Transcription Factor 1; IV: mucosal layer: microvilli on cell surface; mit: mitochondria; N: nucleus; BC: goblet cells; ER: endoplasmic reticulum.