A recent study, led by Dr. Roberto Pacifici from Emory University in Atlanta (USA), suggests that probiotics may have potential as a therapeutic strategy for preventing steroid deficiency-associated bone loss in mice.
The researchers studied the relationship between gut bacteria and the bone loss induced by estrogen deficiency in three groups of female mice: germ-free, conventional and colonized mice (mice raised in a germ-free environment until 4 weeks of age and then colonized with conventional microbiota). Sex steroid deficiency was induced pharmacologically through treatment with leuprolide, which is a synthetic hormone used to decrease levels of certain hormones in mice produced by the testes and ovaries, including estrogens.
Germ-free (GF) mice were protected against the trabecular bone loss induced by sex steroid deficiency, showing higher trabecular numbers, lower trabecular space, and similar trabecular thickness as compared with conventional and colonized mice. Besides this, GF mice were also protected against the increase in bone turnover induced by sex steroid deprivation. Leuprolide treatment induced a significant increase in indices of bone resorption in conventional and colonized mice, but not in GF mice, which indicates that the gut microbiota is required for leuprolide to increase bone resorption. Sex steroid deficiency increased gut permeability, expanded Th17 cells (CD4+IL-17A+ cells), and increased levels of osteoclastogenic cytokines tumour necrosis factor alpha (TNF-a), receptor activator of nuclear factor kappa-B ligand (RANKL), and interleukin (IL)-17 in the small intestine and the bone marrow. These data revealed that GF mice were not only protected against the estrogen deficiency-induced bone loss, intestinal and bone marrow inflammatory responses, but also against increased gut permeability that occurred in conventional and colonized mice.
Furthermore, four-week treatment of conventionally raised mice with the probiotics Lactobacillus rhamnosus GG (LGG) or with a commercial probiotic containing eight strains of live bacteria –Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. bulgaricus, and Streptococcus thermophilus– protected against bone loss, increased gut permeability, and intestinal and bone marrow inflammation induced by estrogen deficiency. In contrast, treatment with non-probiotic strains of bacteria (a strain of Escherichia coli and a mutant LGG) did not prevent estrogen deficiency-induced bone loss.
In summary, gut bacteria may play a role in enhancing inflammatory responses induced by sex steroid deprivation. Treatment with probiotics may prevent the bone loss, the increase in gut permeability, and the intestinal and bone marrow inflammation induced by sex steroid depletion.
Li JY, Chassaing B, Tyagi AM, et al. Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest. 2016. doi:10.1172/JCI86062.