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/IL17Aâmediated 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: SFBâmonoassociated mice versus germâfree (GF) mice and specificâpathogenâfree (SPF) mice +/â SFB. SFB colonization was validated by 16S rDNA analysis, and SFBâinduced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFBâcolonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFBâcolonized mice had increased expression of proinflammatory chemokines and acuteâphase reactants in the liver. Lipocalinâ2 (LCN2), an acuteâphase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFBâcolonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gutâliverâbone axis. Proinflammatory TH17 and TH1 cells were increased in liverâdraining lymph nodes of SFBâcolonized mice, which further substantiates that SFB osteoimmuneâresponse effects may be mediated through the liver. SFBâinduction 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. Š 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.