A recent study published in Cell Host & Microbe identifies a potential obesity-linked bacterium, Megamonas, from a large-scale cohort of obese individuals in China. This research suggests potential strategies for future obesity management by illustrating how the bacterium degrades intestinal myo-inositol, enhances lipid absorption, and contributes to obesity.

towfiqu-barbhuiya-J6g_szOtMF4-unsplash (1)

The study is jointly conducted by Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, BGI Research, and BGI Genomics Institute of Intelligent Medical Research (IIMR).

READ MORE: Specific bacteria in your gut are involved in compulsive eating and obesity

READ MORE: Gut bacteria that strongly influence obesity are different in men and women, study finds

“Through a large-scale study of intestinal metagenome and host genome in obese Chinese, this research reveals a strong link between gut Megamonas and obesity,” said Dr. Yang Fangming, co-first author from BGI Genomics. Dr. Yang adds, “The research uncovers the mechanism by which Megamonas induces obesity, providing a new target bacterium for the diagnosis and treatment of obesity.”

Metagenomic sequencing

The researchers performed metagenomic sequencing on fecal samples from 1,005 individuals, including 631 obese individuals and 374 normal-weight individuals, and conducted whole-genome sequencing (WGS) on 814 of these participants. They reveal a strong link between Megamonas and obesity—the combination of Megamonas and host genetic risk factors significantly increased the likelihood of obesity.

In the analysis, comprising both obese and normal-weight participants, metagenomic sequencing showed a notable increase in Megamonas in the intestines of obese individuals. All of the samples were further categorized into three enterotypes based on core genera: Bacteroides, Prevotella, and Megamonas. Individuals with the Megamonas-dominated enterotype had higher BMI and a greater incidence of obesity.

Gut microbial imbalance

WGS was performed on 814 individuals to explore the influence of Megamonas across various genetic obesity risk backgrounds. The researchers discovered that gut microbial imbalance has a more significant impact on obesity in individuals with low genetic risk. They concluded that Megamonas has an additive effect with host genetics on obesity.

Low-Res_BGI Genomics Obesity Gut Microbiota

Source: BGI Genomics

Figure S1. Study design, data analysis and experimental strategy for linking the human gut microbiota, genetics, and obesity. Related to STAR Methods.(A) Basic information of a Chinese obese cohort (n = 1,005).(B) Shotgun metagenomic sequencing and taxonomic profiling analysis on 1,005 collected fecal samples.(C) Whole genome sequencing conducted on 814 collected blood samples, and the calculation of polygenic risk score (PRS) for BMI based on BMI-associated common variants.(D) Identification of obesity-enriched microbial taxa, and assessment of the impacts of gut microbiota and host genetics on obesity.(E) Experimental design of functional examination of M. rupellensis and E. coli with heterologous expression of a myo-inositol-degrading enzyme in vitro and in vivo.

The findings were further supported by animal studies. Megamonas rupellensis significantly increased weight and fat accumulation in mice on a high-fat diet. The bacterium degrades myo-inositol, a compound that effectively inhibits fatty acid transport. Its degradation enhances intestinal fat absorption, leading to obesity.

BGI Genomics’ whole genome sequencing (WGS) service detects the complete genome sequence at one time and provides a high-resolution, base-by-base view of the genome. This enables researchers to see both large and small variants and identify potential causative variants for further follow-on gene expression or regulation mechanism studies.

Topics