The Role of the Gut Microbiome in Mediating Obesity

Connie Hsiao

 Introduction.  Obesity is a condition characterized by excessive adipose tissue and increases an individual’s risk for health, social and mental issues. Obesity is a major issue in the United States, where more than one-third of Americans are clinically obese (BMI ≥ 30 kg/m2).1 Environmental and genetic factors both affect an individual’s propensity for weight gain and obesity.2-5 Research has implicated the gut microbiome as a critical determinant of nutrient uptake, metabolism and weight.6 Studies have suggested that diet can account for up to 57% of microbial variation. Increased levels of Firmicutes, decreased levels of Bacteroidetes, and chronic low-grade inflammation associated with a loss of Actinobacteria have been correlated with increased weight and fat mass.7-10 Further research into the role of the gut microbiome may be critical to understanding and treating obesity.  Methods.  Germ-free mice were colonized with uncultured fecal microbiota from each member of four twin mice pairs discordant for obesity. Recipient mice were fed one of three diets that varied in fat, plant polysaccharide, fruit and vegetable content. Lean or obese mice were cohoused 5 days after colonization. Body composition changes were defined by quantitative magnetic resonance. Microbiota or microbiome structure, gene expression, and metabolism were assayed by 16S ribosomal RNA profiling, whole-community shotgun sequencing, RNA- sequencing, and mass spectrometry. Host gene expression and metabolism were also characterized.  Results.  Obese mice conveyed significantly greater increases in body mass and adiposity than lean mice. Differences in body composition were correlated with increased short-chain fatty acids (SCFA), increased plasma lipopolysaccharide (LPS) and increased cytokine production in obese mice.7-9 An increased Firmicutes to Bacteroidetes ratio is correlated to increased SCFA levels, leading to enhanced lipogenesis and storage of calories as fat.8 High fat diets increased gut permeability to LPS, causing metabolic endotoxemia and systemic inflammation, which was associated with a loss of gut Actinobacteria.7,8 Cohousing lean and obese mice prevented development of increased adiposity and body mass in obese mice and transformed their microbiota’s metabolic profile to a leanlike state.10 The transformation from an obese to lean profile correlated with invasion of Bacteroidetes and was diet-dependent.  Conclusions.  Studies have revealed that transmissible and modifiable interactions between diet and microbiota can influence host weight gain and adiposity. A microbiota characterized by increased Firmicutes and decreased Bacteroidetes and Actinobacteria levels contribute to an obese metabolic profile by increasing SCFA production, plasma LPS levels, and inflammation.

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