Helpful intestinal bacteria may stimulate bone formation via butyrate, according to a recent paper in Immunity. Butyrate increases bone formation through its regulation of T cells, Emory researchers report.

The finding adds to evidence for beneficial effects of butyrate and other SCFA (short chain fatty acid) metabolites, which are produced by bacterial fermentation of fiber in the intestines.

Roberto Pacifici and colleagues had observed that probiotic supplements protected female mice from the loss of bone density occurring after ovary removal, a simulation of the hormonal changes of menopause. Probiotic bacteria could also stimulate bone formation in mice with intact ovaries, the researchers found.

The new Immunity paper shows how this effect is produced. The probiotic bacteria do not make butyrate themselves, but they encourage the growth of other Clostridum bacteria that do produce butyrate.

Butyrate has a complex set of effects depending on the cell type, but in this case, it appears to be acting through Wnt10b and regulatory T cells. Butyrate by itself can stimulate bone formation in germ-free mice, but the probiotic LGG bacteria can’t: other intestinal bacteria are necessary for the probiotics’ effect.

Among chemists, butyrate is known for its odor — like rancid butter.

The investigators also report that the mice disliked the taste of butyrate (it is well known for its odor), and had to slowly build up the dose so that they would get used to it.

The authors conclude:

An increase in the number of Treg cells is achievable by nutritional supplementation with the probiotic LGG, butyrate or other SCFAs. Thus, an increase in the number of Treg cells via nutritional supplementation may represent a therapeutic modality for increasing bone mass and preventing osteoporosis. Moreover, the use of probiotics or butyrate to increase the number of Treg cells may find wider applications, such as in transplant medicine or as a treatment for inflammatory and autoimmune conditions.