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Menaka Thounaojam, Allston Oxenrider, Tommy Bui, Ravirajsinh Jadeja, Pamela M Martin, Manuela Bartoli; Altered bile acids-gut microbiome axis in oxygen-induced retinopathy: potential implications for retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 2022;63(7):803 – F0362.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies by our group and others have shown a significant role of bile acids (BA) in various retinal diseases. Gut microbiota has been shown to profoundly affect BA metabolism and systemic composition due to bacterial bile salt hydrolases (BSH). Dysregulated BA-gut microbiome axis (BGA) contributes to various pathologic conditions, including diabetic retinopathy. In addition, exogenous administration of the BA ursodeoxycholic acid (UDCA) has been shown to balance gut microbiota and, from our studies, to ameliorate oxygen-induced retinopathy (OIR), an experimental model of retinopathy of prematurity (ROP). Here, we have investigated whether OIR in mice alters the BGA and whether treatment with UDCA could normalize it.
Seven days-old mice pups (P7) were subjected to OIR. A group of OIR mice was treated with 50 mg/kg/day of UDCA administered ip. from postnatal days 7 to 17 (P7–P17). Age-matched fully untreated (RA) mice were used as control. BA and microbiome composition was assessed in cecal samples of mice at P17 in all experimental groups, using LC-MS/MS and 16S sequencing, respectively. Spearman’s rank correlation coefficient was assessed to determine the specific association of altered BA profile with relative microbiome composition. In addition, levels of BSH activity and systemic insulin-like growth factor 1 (IGF-1) were analyzed in all experimental groups.
BA composition in cecal samples of OIR mice at P17 showed increased levels of unconjugated BA in OIR mice and decreased glycine and taurine conjugated BA, indicating dysregulated BA metabolism. In addition, microbiome composition in OIR mice was significantly disrupted with higher levels of Proteobacteria and lower composition of BSH-producing phyla such as Firmicutes and Bacteroidetes compared to control mice (RA). Furthermore, Spearman’s rank correlation coefficient analysis confirmed a significantly dysregulated BGA in OIR. Finally, UDCA treatment of OIR mice corrected the BA-gut microbiome dysregulation. These changes were further associated with a significant decrease in serum IGF-1 levels and increased cecal BSH enzymatic activity in OIR+UDCA mice compared to OIR mice.
Our experimental data evidence a potential correlation between dysregulated BGA and ROP and suggest UDCA as an effective therapy to correct BA-gut microbiome dysregulation in ROP.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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