Lymphocytes mediate bone loss induced by gut microbiota repopulation following antibiotic use

Abstract

Recent studies link the gut microbiota, immune cells and bone health. We identified that treatment of mice with oral antibiotics followed by four weeks of natural repopulation leads to an altered gut microbiota composition as well as bone loss. To identify the role of lymphocytes in post‐ABX repopulation induced bone loss, we treated T and B lymphocyte‐deficient Rag knockout mice and corresponding wild‐type (WT) mice (male, C57BL/6J, 12 weeks of age) with antibiotics (ABX, ampicillin (1g/L) and neomycin (0.5g/L)) in the water for two weeks. Afterwards, mice received water without antibiotics for another 4 weeks to allow the repopulation of gut microbiota. Bone volume fraction (BVF) of the femurs were analyzed using microcomputed tomography. Our results demonstrate a significant decrease in post‐ABX WT mouse femoral trabecular BVF (relative to body weight (BW)) (WT:0.98±0.05, WT‐ABX: 0.69±0.07, n=14–17). Strikingly, this effect was not observed in the RAG‐KO (BVF/BW KO: 1.57±0.07, KO‐ABX: 1.49±0.11, n=9–11) mice. Analysis by diversity metrics (Bray‐Curtis) showed similar changes in gut microbiota repopulation in both the WT and RAG‐KO group. However, several operational taxonomic units (OTUs) classified as Lactobacillales were significantly higher in the repopulated RAG‐KO group when compared to the WT group (WT‐ABX: 0.24±.07, KO‐ABX:2.63±.31, n=11–14). This suggests that Lactobacillales might play a protective role in preventing bone loss during post‐ABX repopulation in the RAG‐KO mice. To test this possibility, we administered Lactobacillus reuteri 6475 for 4 weeks to post‐ABX‐treated WT mice. Our data establish that Lactobacillus reuteri 6475 can colonize the gut in the WT mice and more importantly, it prevents bone loss induced by post‐ABX repopulation. Together, our results demonstrate an important role for lymphocytes in regulating bone health and for the role of Lactobacillus reuteri 6475 to prevent bone loss in ABX‐treated mice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.