Severe Obesity, Psychopathologies, and Gut Microbiota: Insights into Bariatric Surgery Outcomes

Background: Severe obesity is associated with alterations in gut microbiota (GM), yet the influence of co-occurring psychological factors on GM composition and weight-loss outcomes following bariatric surgery (BS) remains insufficiently understood. Objective: This study aimed to determine whether psychological variables—including adverse childhood experiences (ACEs), depression, and binge eating—are associated with baseline GM profiles and whether they collectively contribute to variability in postoperative weight-loss outcomes. Methods: We prospectively included 132 individuals with severe obesity (mean age=48.3±0.1 years, mean BMI=44.3±0.02 kg/m²), who underwent BS and had a follow-up of at least one-year post-BS. GM profiles were analyzed using nanopore sequencing technology. Baseline clinical and psychopathological phenotypes, including depression, eating disorders, and past traumatic history, were collected as well as weight-loss trajectories using K-means clustering. Results: ACEs, but not depression or binge eating, were significantly associated with reduced microbial richness (p=0.017), with a dose-response relationship observed based on the number of reported ACEs. Nineteen species-level genome bins (SGBs), including several Bifidobacterium spp., were depleted in patients with ACEs. Depression and eating disorders were not associated with distinct GM metagenomic signatures, yet no differences in GM richness. While, weight-loss outcomes were not influenced by psychological factors, distinct GM signatures were associated with different weight-loss trajectories. Conclusion: ACEs are associated with GM alterations in individuals with severe obesity but do not adversely affect weight-loss outcomes following BS. Rather, specific preoperative GM compositions, independent of psychological status, may potentially serve as predictive biomarkers for both short- and mid-term surgical success. These findings highlight the potential of integrating microbiome profiling into preoperative assessments to guide future personalized therapeutic strategies.