| Summary: | Obesity is best understood as a multifactorial metabolic imbalances disorder. In a cross-sectional study, we aimed to explore sociodemographic and dietary determinants of obesity in relation to brain-gut homeostasis among overweight and obese individuals. Multivariate logistic regression models were used to examine obesity and its association with sociodemographic and dietary factors. Biological variables examined included the gut microbiome, fecal amino acid metabolites and brain structural volumes. Among 130 participants, there were higher odds of obesity if individuals were Hispanic (adjusted odds ratio (aOR) 1.56, <i>p</i> = 0.014). Compared to non-Hispanics, Hispanics differed in gut microbial composition (<i>p</i> = 0.046) with lower microbial species richness (Chao1) (<i>p</i> = 0.032) and evenness (Shannon) (<i>p</i> = 0.0029). Fourteen of the twenty fecal amino acids including branch-chain- and aromatic- amino acids were increased among Hispanics (<i>q</i> < 0.05). Brain structural volumes in reward regions were decreased in Hispanics (pallidum, <i>q</i> = 0.036; brainstem, <i>q</i> = 0.011). Correlation patterns suggest complex brain-gut interactions differ by Hispanic ethnicity. In conclusion, Hispanics expressed a unique brain-gut microbial signature, which was associated with obesity despite sociodemographic and dietary differences. Addressing ethnic disparities guided by biologic phenotypes may unlock novel understanding of obesity heterogeneity and treatment strategies.
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