Alterations to the Gut Microbiome Prevent Glucocorticoid Induced Osteoporosis

Glucocorticoids are important anti‐inflammatory drugs that can have significant side effects including glucocorticoid‐induced osteoporosis (GIO). Glucocorticoids directly induce apoptosis of osteoblasts and osteocytes but have also been shown to alter the gut microbiota composition. Previously, our lab and others have shown that the microbiota is involved in the regulation of bone density, however, little is known about the role of the gut in regulating GIO. Therefore, we investigated the role of microbiota alterations in GIO. Male C57BL/6J (16‐weeks‐old) mice received 8‐weeks of glucocorticoid treatment (GC, 2.5 mg/kg/day, slow release pellet subQ) with or without chronic antibiotic treatment (ABX, ampicillin and neomycin) to deplete the microbiota. Strikingly, the ABX‐GC mice did not lose bone, whereas the non‐ABX GC mice lost 40% trabecular bone volume. Based on this previously unknown link between microbiota and GIO, we examined if GIO can be prevented by using probiotics to modify the microbiota of the GC mice. Male mice were GC treated with or without oral Lactobacillus reuteri (LR; 108 cfu/day) supplementation. After 8 weeks, analyses of stool and colon samples revealed that LR treatment significantly alters the microbiota composition compared to GC treated mice. More importantly, LR treatment prevented GIO. Analyses of intestinal permeability established that GC treatment increases intestinal permeability, an outcome that was prevented by treatment with chronic ABX and LR. To determine if intestinal barrier function was mechanistically important for GIO, we treated GC‐mice with a mucus supplement (MDY). Strikingly, enhancement of barrier function prevented both GC‐induced barrier dysfunction and GIO. Together these data highlight the unappreciated role of the gut microbiota in GIO pathogenesis, and identify novel therapeutic targets for preventing GIO.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.