MON-582 Gavage of Rats with the Human Duodenal Microbe Rothia mucilaginosa Leads to Metabolic Disturbances that are Reversible on Cessation

Abstract Disclosure: G. Parodi: None. G. Leite: None. G. Barlow: None. I. Rivera: None. M. Sanchez: None. M. Villanueva Millan: None. S. Mahravar: None. A. Trujillo: None. B. Pedroza: None. C.M. Fajardo: None. M. Pimentel: None. R. Mathur: None. We have previously demonstrated that Rothia mucilaginosa, a Gram-positive bacterium commonly found in the human duodenum, produces testosterone in vitro. Furthermore, female rats gavaged with R. mucilaginosa developed metabolic disturbances including insulin resistance, independent of weight gain. Here, we attempt to prove Koch’s postulates and reverse the metabolic effects of R. mucilaginosa in female rats. Methods: Reproductive age female rats were gavaged with 108 CFU/mL R. mucilaginosa or PBS (controls) daily for 4 weeks. After 4 weeks, half of the R. mucilaginosa gavaged rats and half of the control rats were euthanized. All remaining rats were gavaged with PBS alone for another 4 weeks, followed by euthanasia. Rats were weighed and fasting serum was collected at each euthanasia. Fasting insulin and glucose were measured by ELISA, and HOMA-IR index was calculated. Results: After the initial 4-week gavage period, there was no significant difference in body weight between R. mucilaginosa gavaged rats (n=40, 227.40±10.71g ) and controls (n=40, 233.00±14.08g, P=0.17). R. mucilaginosa gavaged rats exhibited higher levels of fasting glucose (99.70±12.67 mg/dL vs. 89.17±15.73 mg/dL, P=0.0019) and fasting insulin (2.95±1.77 μIU/mL vs. 2.14±1.26 μIU/mL, P=0.025), and resulting higher HOMA-IR index (0.73±0.46 vs. 0.48±0.34, P=0.01), when compared to controls. 4 weeks after the last gavage with R. mucilaginosa, body weights remained similar in rats originally gavaged with R. mucilaginosa (n=20, 246.00±12.43g) and controls (n=20, 251.80±14.99g, P=0.19). At this timepoint, there were no significant differences between groups for fasting glucose levels (110.30±12.79 mg/dL vs. 106.60±10.25 mg/dL, P=0.32), fasting insulin levels (5.66±3.03 μIU/mL vs. 4.82±2.57 μIU/mL, P=0.36), or HOMA-IR index (1.57±0.93 vs. 1.28±0.71, P=0.29). Conclusion: Here we show that daily gavage with the Gram-positive duodenal bacterium R. mucilaginosa can induce metabolic consequences in rats, including higher fasting glucose, insulin, and HOMA-IR index. These effects are reversed following cessation of gavage with R. mucilaginosa. Presentation: Monday, July 14, 2025