Chinese researchers identify mechanism behind obesity-inducing bacteria

BEIJING -- In daily life, some people can eat voraciously and still appear slim, while others seem to gain weight with every bite and are naturally prone to obesity.

This observation is now backed by a recent finding from Chinese researchers, published in the journal Cell Host & Microbe, which suggests that the underlying cause might be Megamonas, a family of obesity-causing bacteria.

A team of researchers from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, BGI Research, and the Institute of Intelligent Medical Research under BGI Genomics has identified the potential obesity-causing bacteria and revealed the underlying mechanisms in a large-scale cohort of obese individuals in China, the China Science and Technology Daily reported Monday.

IDENTIFYING BACTERIA

Numerous studies have highlighted the critical roles of gut probiotics in obesity. However, the specific microbes contributing to obesity and the underlying mechanisms remain undetermined.

The research team conducted shotgun metagenomic sequencing on fecal samples from a cohort of 631 obese individuals and 374 normal-weight controls, identifying a Megamonas-dominated cluster of microbes enriched in the obese subjects.

The researchers identified three enterotype-like clusters among the 1,005 samples — Bacteroides, Prevotella and Megamonas. Individuals enriched with Megamonas exhibited higher Body Mass Index (BMI) and a greater proportion of obesity compared to the other two types.

Further analysis revealed that three species of Megamonas are all positively correlated with body weight, waist circumference, and BMI. Therefore, the research team determined a significant association between Megamonas and obesity.

GENETIC RISK

Based on the findings about obesity-inducing Megamonas, the research team investigated the impact of Megamonas in populations with different genetic risks for obesity.

The study found that in the population with low genetic risk for obesity, the impact of Megamonas on BMI is significantly higher than in the population with high genetic risk.

Furthermore, the differences in gut microbiota between the obese group and the normal control group are more obvious in the population with a low genetic risk for obesity.

According to Wu Chao, the first author of the study and a researcher at Shanghai Jiao Tong University School of Medicine, the findings indicate that for populations with a low genetic risk for obesity, the impact of gut microbiota on the occurrence of obesity is greater than for those with a high genetic risk.

UNDERLYING MECHANISM

To unveil the mechanism behind the obesity-causing bacteria, the research team conducted further experiments using various models such as specific-pathogen-free (SPF) mice, germ-free (GF) mice, and small intestinal organoids, with M. rupellensis, a representative species of Megamonas, serving as the experimental feeding agent.

Animal experiments revealed that M. rupellensis had no significant effect on the body weight of SPF mice fed a normal diet, but it significantly promoted weight gain and fat accumulation in SPF mice on a high-fat diet.

In the GF mouse model on a high-fat diet, M. rupellensis also significantly increased body weight and could markedly promote intestinal fatty acid transport and lipid absorption.

The team of researchers has also verified the ability of M. rupellensis to degrade inositol both in vitro and in vivo. Inositol can inhibit the efficiency of fatty acid transport. This suggests that the obesity-inducing effect of M. rupellensis may be mediated through the degradation of inositol.

According to Yang Fangming, the co-first author of the article and a researcher at BGI, the study revealed a strong association between Megamonas and the occurrence of obesity and clarified the mechanism by which Megamonas induces obesity.

Yang said that the study is expected to provide a new target bacteria for the diagnosis and treatment of obesity in the future.