Title

Post-antibiotic gut dysbiosis-induced trabecular bone loss is dependent on lymphocytes.

Document Type

Article

Publication Date

2-21-2020

Publication Title

Bone

Abstract

Recent studies in mouse models have shown that gut microbiota significantly influences bone health. We demonstrated that 2-week oral treatment with broad spectrum antibiotics followed by 4 weeks of recovery of the gut microbiota results in dysbiosis (microbiota imbalance)-induced bone loss in mice. Because gut microbiota is critical for the development of the immune system and since both microbiota and the immune system can regulate bone health, in this study, we tested the role of the immune system in mediating post-antibiotic dysbiosis-induced bone loss. For this, we treated wild-type (WT) and lymphocyte deficient Rag2 knockout (KO) mice with ampicillin/neomycin cocktail in water for 2 weeks followed by 4 weeks of water without antibiotics. This led to a significant bone loss (31% decrease from control) in WT mice. Interestingly, no bone loss was observed in the KO mice suggesting that lymphocytes are required for dysbiosis-induced bone loss. Bray-Curtis diversity metrics showed similar microbiota changes in both the WT and KO post-antibiotic treated groups. However, several operational taxonomic units (OTUs) classified as Lactobacillales were significantly higher in the repopulated KO when compared to the WT mice, suggesting that these bacteria might play a protective role in preventing bone loss in the KO mice after antibiotic treatment. The effect of dysbiosis on bone was therefore examined in the WT mice in the presence or absence of oral Lactobacillus reuteri treatment for 4 weeks (post-ABX treatment). As hypothesized, mice treated with L. reuteri did not display bone loss, suggesting a bone protective role for this group of bacteria. Taken together, our studies elucidate an important role for lymphocytes in regulating post-antibiotic dysbiosis-induced bone loss.

PubMed ID

32061677

Volume

134

First Page

115269

Last Page

115269

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