The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses.The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6-to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline-versus vehicle-treated germfree mice had similar alveolar bone loss outcomes, implying that antimicrobialdriven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring