About this item:

416 Views | 554 Downloads

Author Notes:

Address correspondence to: Roberto Pacifici, Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, 101 Woodruff Circle, Room 1309, Atlanta, Georgia 30322, USA. Phone: 404.712.8420; E-mail: roberto.pacifici@emory.edu

JYL, MNW, JGM, ATG, RMJ, and RP designed the studies.

JYL, BC, AMT, CV, TL, JA, and TMD performed the research and analyzed the data.

RP and RMJ wrote the manuscript.

The authors have declared that no conflict of interest exists.

Subjects:

Research Funding:

This study was supported by grants from the NIH (R. Pacifici: R01AR54625, R01DK091780, DK007298, and RR028009; J.Y. Li: AR061453; R.M. Jones: R01DK098391; M.N. Weitzmann: R01AR059364, R01AG040013, R01AR068157, and R01AR068157).

B. Chassaing is a recipient of the Career Development award from the Crohn’s and Colitis Foundation of America (CCFA).

M.N. Weitzmann was also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • BLOOD MONONUCLEAR-CELLS
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • INTERMITTENT PTH TREATMENT
  • EARLY POSTMENOPAUSAL WOMEN
  • ESTROGEN-RECEPTOR-ALPHA
  • LOSS IN-VIVO
  • TNF-ALPHA
  • T-CELLS
  • GUT MICROBIOTA
  • INTESTINAL PERMEABILITY

Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics

Show all authors Show less authors

Tools:

Journal Title:

Journal of Clinical Investigation

Volume:

Volume 126, Number 6

Publisher:

, Pages 2049-2063

Type of Work:

Article | Final Publisher PDF

Abstract:

A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.

Copyright information:

© 2016, American Society for Clinical Investigation.

Export to EndNote