Obesity: Is a bacterial fatty acid involved?

As the prevalence of obesity and associated metabolic disorders increases worldwide, dietary changes are not enough for many patients. Understanding the impact of other environmental factors is crucial to developing alternative treatment strategies. Numerous studies point to a link between dysbiosis of the gut microbiota and the development of obesity, which could at least partly explain the variations from one individual to another in terms of susceptibility to metabolic diseases. However, the molecular mechanisms and the causal link between the bacteria of the gut microbiota, especially their metabolites, and the development of obesity are not fully understood.

High-fat diet and Fusimonas intestini: A synergistic effect on weight gain

It is well accepted that a diet high in fat, especially saturated fat, increases the risk of obesity and its metabolic comorbidities. But we do not know to what extent certain metabolites (such as long-chain fatty acids) produced by the bacteria of the gut microbiota influence the pathogenesis of these conditions. A Japanese team looked at the Lachnospiraceae, a bacterial family in the gut microbiota linked with obesity and type 2 diabetes in previous studies. The team showed that one of the bacterial family’s commensal species, Fusimonas intestini, is significantly more present in cases of obesity and hyperglycemia, in both mice and humans.

To identify a potential causal link between this species and obesity, the researchers compared mice whose gut microbiota was colonized by Escherichia coli and F. intestini or by E. coli alone, fed a normal or high-fat diet. They found a significant increase in body weight and body fat only in those mice fed the high-fat diet and colonized with F. intestini, even in very small amounts. In addition, these mice had elevated levels of plasma cholesterol and of expression of pro-inflammatory TNF-α, lipopolysaccharide-binding proteins, and genes encoding for leptin. By colonizing gnotobiotic mice with F. intestini and 9 species representative of the human microbiota, the researchers found this fat gain. These results suggest that high dietary fat intake and F. intestini act synergistically to change the host metabolism.

Altered lipid metabolism and intestinal impermeability

The researchers found that F. intestini produced an abundance of various long-chain fatty acids. On the high-fat diet, the gut microbiota colonized by this bacteria contained twice as much elaidate, a trans fatty acid that is known to increase the risk of cardiovascular disease, obesity and insulin resistance. It also had more saturated fatty acids such as palmitate, stearate and margarate. According to the researchers, the high-fat diet leads to an overexpression of microbial genes involved in lipid production, in particular FadR (Fatty acid metabolism regulator), which regulates fatty acid metabolism. Their blood and tissue analyses suggest that metabolites of F. intestini degrade the intestinal barrier, leading to endotoxemia that promotes the development of obesity.