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Li et al. Post menopausal bone loss: could probiotics help?

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DOI:10.1038/bonekey.2016.67

Li et al. reveal that mice treated with drugs to block the production of sex steroids exhibited an increased permeability of the gut, an expanded population of Th17cells and upregulation of tumor necrosis factor alpha (TNF), IL-17 and RANKL in the small intestine and the bone marrow.

The findings exactly the opposite in germ-free mice with no gut microbiotia. Blocking sex hormone production did not increase expression of cytokines, did not stimulate bone resorption and did not lead to loss of trabecular bone. The authors consider this a clear demonstration that bone loss after removal of sex steroids is mediated by the microorganisms in the gut.

Support for this theory was further obtained by giving probiotic preparations that reduce gut permeability to mice deficient in sex hormones. Mice treated with Lactobacillus rhamnosus GG or the probiotic supplement VSL#3 were completely protected from hormone-dependent bone loss and the signals for inflammation in the gut and bone marrow were significantly reduced.

Editor’s comment: This study proposes that estrogen deficiency increases the intestinal epithelial permeability and enhances antigenic stimulation to immune cells by intestinal microbiota. The authors also demonstrate that probiotics tighten intestinal barrier integrity and protect mice from bone loss. The question arises whether the primary effect of estrogen is on the intestinal tight junction or on the microbota.

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