Perturbation on gut microbiota impedes the onset of obesity in high fat diet-induced mice

• Published in: Frontiers in endocrinology (Lausanne) Vol. 13; p. 795371
• Main Authors: Yu, Zhongjia, Yu, Xiang-Fang, Kerem, Goher, Ren, Pei-Gen
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 09.08.2022
• Subjects: Animals; bioinformatic pipelines; Blood Glucose; Diabetes Mellitus, Type 2 - complications; Diet, High-Fat - adverse effects; Endocrinology; Gastrointestinal Microbiome; jejunal microbiota; Metabolic Diseases - complications; Mice; Mice, Obese; obesity; Obesity - etiology; Obesity - metabolism; perturbation; T2DM; bioinformatic pipelines; T2DM; jejunal microbiota; perturbation; obesity
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2022.795371

High-calorie intake has become one of the most common causes of dietary obesity, which eventually develops into type 2 diabetes mellitus (T2DM). Microbiota, along with the length of the gastrointestinal tract, is related to metabolic disorders, but its shifts and following impact on metabolic disorders due to external perturbation are still unclear. To evaluate shifts of microbiota from the proximal to the distal intestine and their impact on metabolic disorders, we profiled jejunal and colonic microbiota with the perturbation using high salt (HS) and antibiotic-induced microbiota depletion (AIMD) in diet-induced obesity (DIO) mice and analyzed the association with parameters of both obesity and blood glucose. After ten weeks of feeding DIO mice with HS intake and AIMD, they failed to develop obesity. The DIO mice with HS intake had T2DM symptoms, whereas the AIMD DIO mice showed no significant difference in blood glucose parameters. We observed that the jejunal and colonic microbiota had shifted due to settled perturbation, and jejunal microbiota within a group were more dispersed than colonic microbiota. After further analyzing jejunal microbiota using quantified amplicon sequencing, we found that the absolute abundance of  (R = 0.695, p = 0.001) and   (R = 0.631, p = 0.005) in the jejunum was positively correlated with the changes in BW and FBG levels. The predicted pathway of glucose and metabolism of other substances significantly changed between groups (p <0.05). We demonstrated that the onset of obesity and T2DM in DIO mice is impeded when the gut microbiota is perturbed; thus, this pathogenesis depends on the gut microbiota.