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

Abstract

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 Colidextribacter (R = 0.695, p = 0.001) and Faecalibaculum (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.

Depletion of gut microbiota influents glucose metabolism and hyperandrogenism traits of mice with PCOS induced by letrozole

“…This phenomenon impacted the gene expression of the intestinal cecum and the signaling of intestinal glucagon-like peptide 1 (GLP-1), facilitated the utilization of glucose by intestinal cells, and consequently led to an amelioration of blood glucose levels, insulin sensitivity, and liver gluconeogenesis. Additional research has corroborated the finding that mice with diet-induced obesity, subjected to high salt and antibiotic-induced microbiome depletion for a duration of 10 weeks, did not exhibit obesity (40). Further investigations into the underlying mechanisms revealed that the reduction of intestinal microbes following ABX treatment can enhance uptake of glucose in brown adipose tissue (BAT) and cecum (41).…”

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice

“…In line with this, we also noted a decreased abundance of the Colidextribacter genus in mice treated with essential oils, particularly among those receiving the highest dose of oregano-derived essential oil. Notably, the presence of this genus is considered indicative of obesity and T2DM [ 43 ].…”

How hypoxia affects microbiota metabolism in mice

“…In a high-fat diet-induced gut microbiota sequencing of obese mice, Colidextribacter and Faecalibacterium were found to be indicators of obesity and their abundance was positively correlated with obesity. Therefore, we speculate that the occurrence of obesity in the normoxic group may be related to the disruption of the gut microbiota induced by Faecalibacterium (Yu et al, 2022). Pyrimidine and purine nucleotide metabolism disorders predominate, suggesting that under conditions of cellular damage (inflammation, hypoxia, acute injury), ATP is rapidly released from cells into the extracellular compartment, causing a rapid increase in extracellular levels of ATP, ADP, or AMP, and adenosine produced by hydrolysis (Fredholm, 2007).…”