MON-825 Sexual Dimorphism of Small Intestinal Microbial Communities

Abstract Disclosure: M. Rashid: None. G. Leite: None. G. Parodi: None. G.M. Barlow: None. A. Hosseini: None. D. Brimberry: None. D. Flor: None. M. Sanchez: None. I. Rivera: None. M. Pimentel: None. R. Mathur: None. There has been growing interest in the sexual dimorphism of the small bowel microbiome, particularly how sex hormones affect microbial communities and lead to the development of disease. While single microbial species can undoubtedly have effects, complex interactions between multiple species within a community (networks) often play more significant roles. Here we compared the duodenal microbial networks of male and female adults. Methods: Duodenal aspirates (DA) were collected from subjects undergoing upper endoscopy without colon prep using a protected double-lumen catheter to avoid cross-contamination from the upper gastrointestinal tract. Males (M) and females (F) were matched for age (±3yrs) and BMI (±3kg/m2). Subjects with gastric bypass surgery, small intestinal bacterial overgrowth, diabetes, current metformin use or antibiotics within 3 months of endoscopy were excluded. DA DNAs were isolated using MagAttract PowerSoil DNA Kits, and V3/V4 libraries were sequenced on a MiSeq. Sparse correlations for compositional data (SparCC) were used to analyze microbial networks, and Gephi was used for statistical analysis and visualization of networks. Results: 133 M (age=55.6±14.7 yrs, BMI=25.1±4.6 kg/m2) and 133 F (age=55.6±14.9 yrs, BMI=24.8±5.0 kg/m2) were compared. Six distinct duodenal microbial communities were identified in M and five in F. Despite having more communities, network diameters were smaller in M (6) than in F (7) and exhibited increased interconnectivity between microbes, with greater closeness to centrality (P<0.0001), but network eccentricity was significantly higher in F vs M (P<0.0001). Each leader/authority of a microbial community was identified. In M, genus Catonella, followed by the genera Fusobacterium, Prevotella, and Neisseria, were the authorities in one of the most important communities. In F, genus Prevotella, followed by the genera Porphyromonas, Fusobacterium, and Campylobacter, were the authorities in the most critical microbial community. Further, the duodenal microbial network in F included a small but unique microbial community that was not found in M, and which included the genera Rothia and Escherichia/Shigella. In both M and F, the genus Prevotella had the most positive influence on network shape and connectivity. In M, the genera Pseudomonas and Serratia had the most negative influence, whereas the genus Lactobacillus had the most negative influence in F. Conclusion: The duodenal microbial network in F differs from M, with decreased microbial interconnectivity and greater eccentricity, which may be more susceptible to environmental disruption. In F, a unique microbial community is led by Rothia, a bacterial genus with species that produce sex-related hormones. More studies are warranted to understand how microbial communities impact sex-related metabolic pathways and how these changes relate to diseases and disorders. Presentation: Monday, July 14, 2025