Intestinal microbes are necessary for the actions of an important hormone regulating bone density, according to two papers from the Emory Microbiome Research Center. The papers represent a collaboration between Roberto Pacifici, MD and colleagues in the Department of Medicine and laboratory of Rheinallt Jones, PhD in the Department of Pediatrics.

Together, the results show how probiotics or nutritional supplementation could be used to modulate immune cell activity related to bone health. The two papers, published in Nature Communications and Journal of Clinical Investigation, are the first reports of a role for intestinal microbes in the mechanism of action of PTH (parathyroid hormone), Pacifici says.

PTH increases calcium levels in the blood and can either drive bone loss or bone formation, depending on how it is produced or administered. Continuous excessive production of PTH, or primary hyperparathyroidism, is a common endocrine cause of osteoporosis. Yet in another context, intermittent external PTH stimulates bone formation, and is an FDA-approved treatment for osteoporosis – also used off-label for fracture repair in athletes.

In mouse models, PTH drives bone loss only if a specific type of bacteria called segmented filamentous bacteria (SFB) is present in their intestines. These bacteria are needed to induce Th17 immune cells, which migrate from the gut to the bone marrow, where they cause bone loss. Th17 cells are also thought to promote autoimmunity. The Nature Communications study suggests that targeting SFB with antibiotics or blocking T cell traffic could be strategies for treating hyperparathyroidism.

In the context of intermittent PTH, a bacterial metabolite called butyrate — widely available as a nutritional supplement — is required for PTH to stimulate bone formation. Here butyrate is also acting to modulate immune cells, in this case regulatory T cells. The finding converges with previous work from Pacifici’s lab. In a 2018 Immunity paper, they showed that probiotic supplements increase butyrate levels by encouraging the growth of butyrate-producing Clostridium bacteria.