Gut Microbiota and Serum Metabolites in Individuals with Class III Obesity Without Type 2 Diabetes Mellitus: Pilot Analysis.

Background: Gut microbial composition seems to change in association with prediabetes. The purpose of this prospective cross-sectional study was to compare the composition of gut microbiota and energy metabolites between individuals with class III obesity but without type 2 diabetes mellitus (OB) and healthy normal weight controls. Methods: The subjects of this prospective cross-sectional study were participants recruited from a previous clinical trial (No: NCT02325804), with intervention focused on weight loss. We recruited 19 OB [mean age ± standard deviation (SD) was 35.4 ± 7.0 years, mean body mass index (BMI) ± SD was 48.8 ± 6.7 kg/m 2 ] and 23 controls (mean age ± SD was 31.7 ± 14.8 years, mean BMI ± SD was 22.2 ± 1.7 kg/m 2 ). Their fecal microbiota was categorized using specific primers targeting the V1-V3 region of 16S rDNA, whereas serum metabolites were characterized by nuclear magnetic resonance spectroscopy. Multivariate statistical analysis and Random Forest models were applied to discriminate predictors with the highest variable importance. Results: We observed a significantly lower microbial α-diversity ( P  = 0.001) and relative abundance of beneficial bacterium Akkermansia ( P  = 0.001) and the short-chain fatty acid-producing bacteria Eubacterium hallii ( P  = 0.019), Butyrivibrio ( P  = 0.024), Marvinbryantia ( P  = 0.010), and Coprococcus ( P  = 0.050) and a higher abundance of the pathogenic bacteria Bilophila ( P  = 0.018) and Fusobacterium ( P  = 0.022) in OB compared with controls. Notably, the Random Forest machine learning analysis identified energy metabolites (citrate and acetate), HOMA-IR, and insulin as important predictors capable of discriminating between OB and controls. Conclusions: Our results suggest that changes in gut microbiota and in serum acetate and citrate are additional promising biomarkers before progression to Type 2 diabetes. The non-invasive manipulation of gut microbiota composition in OB through a healthy lifestyle, thus, offers a new approach for managing class III obesity and associated disorders. ClinicalTrials.gov identifier: NCT02325804.