Danfeng Lisa Wang

 Introduction. Obesity is a major risk factor contributing to the worldwide burden of disease¹. Recent studies show gut microbial composition differs between lean and obese phenotypes in mice and humans. Lean phenotypes tend to have a greater proportion of Bacteroidetes bacteria, while obese phenotypes tend to have a greater proportion of Firmicutes bacteria^2-3. Such differences in microbial composition may lead to differences in SCFA production, and thus, energy-harvesting abilities by interacting with the free fatty acid receptor 2 (FFAR2) in the colon^4-5. Therefore, human gut microbial composition has potential in clinical weight management. Methods. Cecal SCFAs of ob/ob (obese), ob/+ (lean), and +/+ (lean) littermates were identified and measured by gas-chromatography mass-spectrometry, and caloric content of fecal samples from each group were measured by a bomb calorimeter⁴. FFAR2-/- and FFAR2+/+ (WT) mice were fed high-fat diets that were either supplemented with inulin (fermentable carb) or cellulose (non-fermentable carb). MRI assessed whether weight gain was a function of adipocity levels. Radioimmunoassays quantified gut hormones. qPCR evaluated neuropeptide gene expression levels⁵. Results. Obese mice had more cecal SCFAs and lower fecal energy content than lean mice⁴. Inulin-supplemented mice had lower fat mass, lower liver triglyceride levels, improved glucose tolerance, and increased colonic PYY cells via FFAR2 as compared to their cellulose-supplemented counterparts⁵.  Conslusions. While strong evidence shows SCFAs may enhance energy harvesting to promote an obese phenotype, evidence also exists showing a SCFA-conducive diet increases satiety to promote a lean phenotype^4-5. Additionally, factors that alter the gut microbiome are current areas of research interest in the clinical management of obesity. For example, antibiotic exposure in early life may lead to adverse obesity-related effects such as increased weight gain and central adiposity^6-7, while investigations into the role of pre- and probiotics show mixed results⁸. This recurring complexity and controversial effects of SCFAs in microbial-mediated obesity challenges its efficacy as a potential therapeutic target for weight management and continues to be an active area of both basic and clinical investigation.

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