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.

"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 a co-first author. The senior author adds, "The research uncovers the mechanism by which Megamonas induces obesity, providing a new target bacterium for the diagnosis and treatment of obesity."

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.

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.

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

https://www.cell.com/cell-host-microbe/abstract/S1931-3128(24)00230-0