SUN-733 - Effects of Intranasal Oxytocin on Gut Microbiome Composition in A Clinical Trial of Adults with Obesity

Background:
Obesity is a state of metabolic dysregulation characterized by microbiome dysbiosis, which contributes to inflammation with long-term health consequences. Oxytocin (OT), an anorexigenic hypothalamic peptide under investigation for obesity treatment, has anti-inflammatory properties. In animal models of intestinal inflammation, OT signaling reduced gut inflammation. Whether microbiome changes underpin OT effects is unknown. To date, no study has investigated the effects of OT on gut microbiome composition in adults with obesity. In our randomized, double-blind placebo-controlled trial (RCT), we investigated whether intranasal OT induces anti-inflammatory shifts in microbiome composition, specifically by increasing alpha diversity (microbial diversity within an individual), shifting beta diversity (microbiome composition between individuals), increasing the relative abundance of anti-inflammatory microbial species, and reducing the abundance of pro-inflammatory species.
Methods
We performed an RCT of 8 weeks intranasal OT (24 IU 4 times daily) vs. placebo in 61 adults. Stool samples were collected in 47 participants (59% female, mean±SD age 33.6±6.2 years, mean BMI 36.9±4.9 kg/m2) at baseline and after 4 and 8 weeks of treatment and sequenced using shotgun metagenomics. Alpha and beta diversity were analyzed using Wilcoxon Rank Sum Test and PERMANOVA to assess microbiome composition. Relative abundance of microbial species was assessed with MaAsLin 3 using a mixed model for repeated measures, with fixed effect variables of time (categorical) and treatment and the interaction term of time and treatment, with sex as a covariate.
Results
Alpha diversity did not differ between groups at 4 or 8 weeks (p≥0.69). While there were no significant changes in beta diversity for gut microbiota composition at 4 and 8 weeks (p≥0.152), functional pathways differed between OT and placebo groups at week 4 (p=0.048). There were significant interaction effects of treatment × time showing: 1) an increased prevalence of Roseburia intestinalis in the OT group compared to placebo at week 8 (coefficient=[11.81], q=[0.043]); and 2) a decreased prevalence of Ruminococcus_B gnavus in the OT group compared to placebo at week 4 (coefficient =[-9.04], q<[0.0001]) and week 8 (coefficient=[-8.67], q=[0.0003]).
Conclusions
The significant changes in beta diversity of functional pathways suggests that intranasal OT induces anti-inflammatory shifts in microbiome function in adults with obesity. This anti-inflammatory effect is further supported by evidence that OT increases prevalence of the anti-inflammatory microbe Roseburia intestinalis and decreases prevalence of pro-inflammatory Ruminococcus_B gnavus. To improve our understanding of OT effects, future analyses will include additional measures of GI inflammation (e.g. stool consistency and fecal calprotectin).

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*