Common Probiotic Stimulates Bone Formation in Mice, Study Says

A widely used probiotic, Lactobacillus rhamnosus GG (LGG), stimulated bone formation in mice, according to a recent study.

In this study, LGG, increased bone mass in mice by increasing the serum levels of the short-chain fatty acid butyrate. Butyrate increased the frequency of regulatory T, or Treg, cells in the intestine and bone marrow. The Treg cells stimulated CD8+ T cells to secrete the protein Wnt10b, which helps create bone formation by activating Wnt signaling in osteoblasts.

In contrast, mice that received treatments that inhibited the expansion of regulatory T cells prevented bone formation induced by LGG and butyrate. The findings still have to be replicated in humans, but the authors said LGG and butyrate may represent new interventions for osteoporosis.

In a statement, the authors said that oral LGG supplementation for 4 weeks increased bone formation in female mice by stimulating the growth of butyrate-producing gut bacteria, including Clostridia. Supplementation did not increase bone mass in mice raised in a germ-free environment, suggesting that this probiotic indirectly exerts its effects through the metabolic activity of other intestinal microbes.

The authors wrote that small-scale studies in patients with osteoporosis have reported positive results from dietary supplementation with probiotics. In animals, probiotics can prevent bone loss, but their impact on the skeleton remains less clear.

LGG is a lactobacillus, the most common genus of bacteria with reported probiotic action, the authors said. They wrote that the action of LGG may be generalizable to lactic-acid bacteria.

Senior study author Roberto Pacifici of Emory University said the researchers are motivated to find an inexpensive way to prevent osteoporosis. Osteoporosis has surprisingly poorer treatment prevention initiatives compared with other chronic diseases, and adherence to osteoporosis medications is generally poor or medications aren’t even prescribed to patients who need them. For example, the majority of patients who suffer a heart attack receive a β-blocker to prevent the occurrence of another attack. However, only 23% of patients who suffer a hip fracture will receive a preventative osteoporosis medication to reduce the occurrence of a future fracture.

Many people will not know they have osteoporosis, a skeletal disorder characterized by loss of bone mass, deterioration of bone tissue, and decline in bone quality, until they have a fracture. In some cases, fractures can lead to disability, chronic pain, loss of independence, lower quality of life, and even death. About 21% to 30% of patients who experience a hip fracture die within 1 year.

This study was supported by grants from the National Institutes of Health, the Crohn's and Colitis Foundation of America, and the Office of Research and Development at the Department of Veterans Affairs.

Reference

Tyagi AM, Yu M, Darby TM, et al. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression. Immunity. 2018; 49(4):1-16. doi: 10.1016/j.immuni.2018.10.013