From the gut to the strut: where inflammation reigns, bone abstains
Jameel Iqbal, … , Li Sun, Mone Zaidi
Jameel Iqbal, … , Li Sun, Mone Zaidi
Published April 25, 2016
Citation Information: J Clin Invest. 2016;126(6):2045-2048. https://doi.org/10.1172/JCI87430.
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Commentary

From the gut to the strut: where inflammation reigns, bone abstains

Abstract

In this issue of the JCI, Li et al. show that germ-free mice, when chemically castrated, do not lose bone — a finding that unequivocally establishes a role of gut microbiota in mediating hypogonadal bone loss. Additionally and not unexpectedly, probiotics reversed hypogonadal osteopenia in sex steroid–deficient mice by preventing the disruption of gut barrier function and dampening cytokine-induced inflammation. The authors propose that TNFα is a key mediator; however, it is very likely that other molecules — including IL-1, IL-6, IL-17, RANKL, OPG, and CCL2 — modulate probiotic action. The results of this study highlight the potential for repurposing probiotics for the therapy of osteoporosis. Future placebo-controlled clinical trials will be required to establish safety and efficacy of probiotics in reducing fracture risk in people.

Authors

Jameel Iqbal, Tony Yuen, Li Sun, Mone Zaidi

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Figure 1

Gut microbiota play a fundamental role in bone mass regulation.

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Gut microbiota play a fundamental role in bone mass regulation. (A) Norm...
(A) Normal gut flora in the face of hypogonadism cause a proinflammatory immune response, leading to enhanced production of TNFα, IL-1β, RANKL, and CCL2 — among other cytokines and chemokines — from T cells and phagocytes. (B) These molecules in turn drive osteoclastic bone resorption and decrease bone mass. Estrogen serves to dampen this proinflammatory cascade via the gut through several mechanisms. It augments gap junction and cell-to-cell contacts, thus preventing the microbiota from inducing inflammation. It also directly suppresses proinflammatory T cell production and, indirectly, lowers FSH levels, thus attenuating FSH-induced TNFα production (6). (C) Probiotics decrease TNFα and IL-1β levels and increase the production of IL-10 and OPG. These effects are mediated, in part, through an increase in the number of Tregs and increased TGFβ1, which together can also enhance bone formation. An additional mechanism involves the secretion of estrogen-like compounds from probiotics. These compounds likely recapitulate many of the antiinflammatory actions of endogenous estrogen, such as augmenting epithelial cell contacts.