The gut microbiota is a transmissible determinant of skeletal maturation

• Type of Material: Article
• Authors: Abdul Malik Tyagi, Emory University; Trevor M. Darby, Emory University; Emory Hsu, Emory University; Mingcan Yu, Emory University; Subsashis Pal, Emory University; Hamid Dar, Emory University; Jau-Yi Li, Emory University; Jonathan Adams, Emory University; Rheinallt Jones, Emory University; Roberto Pacifici, Emory University
• Language: English
• Date: 2021-01-12
• Publisher: ELIFE SCIENCES PUBLICATIONS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2021, Tyagi et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.64237
• Title of Journal or Parent Work: ELIFE
• Volume: 10
• Start Page: 1
• End Page: 21
• Grant/Funding Information: This paper was supported by the following grants: National Institutes of Health DK112946 to Roberto Pacifici. National Institutes of Health DK108842 to Roberto Pacifici. National Institutes of Health RR028009 to Roberto Pacifici. National Institutes of Health DK098391 to Rheinallt M Jones.
• Keywords: INTERLEUKIN-17; Life Sciences & Biomedicine; MICE; SEGMENTED FILAMENTOUS BACTERIA; DIVERSITY; Science & Technology; TH17 CELLS; SEQUENCES; Life Sciences & Biomedicine - Other Topics; BONE-FORMATION; Biology; INDUCTION; DIFFERENTIATION
• Research Categories: Health Sciences, Medicine and Surgery; Biology, General; Biology, Microbiology

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.