Associations between the gut microbiome and diet, body composition, and glycemic profiles: a cross-sectional post-hoc analysis of the Personal Diet Study.

BACKGROUND: The gut microbiome is implicated in obesity and type 2 diabetes (T2D), but how diet, body composition, glycemic status, and self-efficacy factors relate to the microbiome in high-risk individuals is not well characterized. The purpose of this post-hoc analysis is to examine the relationship between the gut microbiome and obesity-related metabolic factors, including body composition, resting energy expenditure (REE), and glycemic variability (GV). METHODS: Data for this post-hoc cross-sectional analysis were obtained from adults with prediabetes and obesity enrolled in The Personal Diet study, a 6-month behavioral weight loss study. Pre-intervention assessments (n = 95) included the collection of fecal microbiome profile, demographics, socioeconomic status, physical and metabolic characteristics [fat mass, fat free mass (FFM), continuous glucose monitoring-derived GV, REE], self-efficacy and dietary intake. Gut bacterial alpha diversity, beta diversity, and genus level abundances were associated with these host and lifestyle variables using multivariate regression, permutational multivariate analysis of variance, and correlation analyses. RESULTS: Participants were a mean age of 58 years old, mostly female (75.8%), with a mean BMI of 34.6 kg/m2 and mean HbA1c of 5.7%. Higher FFM was associated with greater alpha diversity, whereas higher BMI was associated with lower diversity (p < 0.05). Dietary factors were the most consistent correlates of gut microbial beta diversity. At the genus level, associations were observed for sex, metformin use, BMI, protein intake, and REE. The Prevotella/Bacteroides ratio was positively associated with total energy, sugar, and carbohydrate intake (g/day) and negatively associated with monounsaturated fat intake (g/day). Glycemic measures and self-efficacy were not associated with any genera. CONCLUSION: In adults with prediabetes and obesity, the gut microbiome at baseline was most strongly associated with diet, with additional associations observed for body composition and selected host characteristics. These findings underscore diet as a key correlate of gut microbiome structure in a high-risk metabolic population and support further development of microbiome-informed precision nutrition strategies for obesity prevention and management.