Fatty acid overproduction by gut commensal microbiota exacerbates obesity

Tadashi Takeuchi1, Keishi Kameyama2, Eiji Miyauchi3

  • 1Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.

Cell Metabolism
|January 18, 2023
PubMed

Insights

Gut bacteria like Fusimonas intestini promote obesity by producing fatty acids that damage the gut barrier. This leads to metabolic endotoxemia and facilitates diet-induced obesity in humans and mice.

Area of Science:

  • Microbiology
  • Metabolic Diseases
  • Gut Microbiome Research

Background:

  • Gut microbes influence obesity and related conditions.
  • The precise mechanisms, particularly involving microbial metabolites, remain unclear.

Purpose of the Study:

  • To investigate the role of specific gut microbes and their metabolites in obesity.
  • To elucidate the mechanistic link between gut commensals and diet-induced obesity.

Main Methods:

  • Analysis of Fusimonas intestini colonization in obese humans and mice.
  • Investigating microbial gene expression related to lipid production (e.g., fadR).
  • Monocolonization experiments with engineered E. coli to assess lipid metabolism impact.

Main Results:

  • Fusimonas intestini is abundant in obese and hyperglycemic individuals.
  • This microbe produces long-chain fatty acids, including elaidate, promoting obesity.
  • Altered microbial lipid metabolism, specifically FadR regulation, exacerbates metabolic phenotypes.
  • Microbe-derived fatty acids compromise intestinal barrier integrity, leading to metabolic endotoxemia.

Conclusions:

  • Gut commensals can drive obesity through the overproduction of specific lipids.
  • Fusimonas intestini and its lipid metabolites represent a novel mechanistic link to obesity.
  • Targeting microbial lipid metabolism may offer therapeutic strategies for obesity and related metabolic disorders.

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