Dataset Information

The gut microbiota is a transmissible determinant of skeletal maturation.

ABSTRACT: Genetic factors account for the majority of the variance of human bone mass, but the contribution of non-genetic factors remains largely unknown. By utilizing maternal/offspring transmission, cohabitation, or fecal material transplantation (FMT) studies, we investigated the influence of the gut microbiome on skeletal maturation. We show that the gut microbiome is a communicable regulator of bone structure and turnover in mice. In addition, we found that the acquisition of a specific bacterial strain, segmented filamentous bacteria (SFB), a gut microbe that induces intestinal Th17 cell expansion, was sufficient to negatively impact skeletal maturation. These findings have significant translational implications, as the identification of methods or timing of microbiome transfer may lead to the development of bacteriotherapeutic interventions to optimize skeletal maturation in humans. Moreover, the transfer of SFB-like microbes capable of triggering the expansion of human Th17 cells during therapeutic FMT procedures could lead to significant bone loss in fecal material recipients.

SUBMITTER: Tyagi AM

PROVIDER: S-EPMC7803376 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The gut microbiota is a transmissible determinant of skeletal maturation.

Tyagi Abdul Malik AM Darby Trevor M TM Hsu Emory E Yu Mingcan M Pal Subhashis S Dar Hamid H Li Jau-Yi JY Adams Jonathan J Jones Rheinallt M RM Pacifici Roberto R

eLife 20210112

Genetic factors account for the majority of the variance of human bone mass, but the contribution of non-genetic factors remains largely unknown. By utilizing maternal/offspring transmission, cohabitation, or fecal material transplantation (FMT) studies, we investigated the influence of the gut microbiome on skeletal maturation. We show that the gut microbiome is a communicable regulator of bone structure and turnover in mice. In addition, we found that the acquisition of a specific bacterial st ...[more]

PMID: 33432923

Similar Datasets

Project description: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.

Dataset Information

The gut microbiota is a transmissible determinant of skeletal maturation.

Publications

The gut microbiota is a transmissible determinant of skeletal maturation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets