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. Read more
AÂ Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria â€“ lactobacilli â€“ activates the same ancient signaling pathway in intestinal cells in both insects and mammals.Â It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).
Asma Nusrat, MD
A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliverÂ that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.
This ideaÂ has advanced experimentally, as demonstrated byÂ twoÂ papers from Jones and Neishâ€™s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.
Nusrat told me Friday her team began investigatingÂ annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria areÂ activating the same molecular signals.Â (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)
In aÂ secondÂ Journal of Clinical Investigation paper published this February, NusratÂ and herÂ colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more