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. Read more
Probiotic supplements can protect female mice from the loss of bone density that occurs after having their ovaries removed, researchers at Emory and Georgia State reported a couple years ago.
Roberto Pacifici, MD
This finding, published in Journal of Clinical Investigation, had clear implications for the treatment of osteoporosis in post-menopausal women. Prompted by external emails, Lab Land learned that the Emory investigators are now continuing their research in the clinic.
Endocrinologist/osteoimmunologist Roberto Pacifici and colleague Jessica Alvarez are conducting a double-blind study for women aged 50-65, using VSL3, a widely available and inexpensive dietary supplement. Participants would take the supplement or placebo for a year. More information is available here.
In mice, the loss of estrogen increases gut permeability, which allows bacterial products to activate immune cells in the intestine. In turn, immune cells release signals that break down bone. It appears that probiotics both tighten up the permeability of the gut and dampen inflammatory signals that drive the immune cells. Read more
A common cause of bone loss is an overactive parathyroid gland, which doctors usually treat with surgery. New research on how excess parathyroid hormone affects immune cells suggests that doctors could repurpose existing drugs to treat hyperparathyroidism without surgery.
The results were publishedÂ October 8 inÂ Cell Metabolism. [My apologies for not posting thisÂ in October.]
“Surgery is sometimes not an appropriate remedy for hyperparathyroidism because of the condition of the patient, and it is also expensive,” says lead author Roberto Pacifici, MD. “Also, the one pharmacological treatment that is available, cinacalcet, is not always the ideal solution. This work could potentially lead to alternatives.”
Roberto Pacifici, MD
Researchers at Emory University School of Medicine led by Pacifici teamed up with doctors from the University of Turin in Italy, combining observations of human patients with an overactive parathyroid with experiments on mice.
The drugs identified as potential treatments are: calcium channel blockers, now used to treat high blood pressure, and antibodies that block the inflammatory molecule IL-17A, under development for the skin disease psoriasis. Clinical trials would be necessary to show that these drugs are effective against parathyroid hormone-induced bone loss in humans. Read more
I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.
However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.
Note for microbiome fans: connections between Th17 cells and intestinalÂ microbes (segmented filamentous bacteria) are strengthening. It gets complicated because gut microbiota, together with Th17 cells, mayÂ influenceÂ metabolic disease and Th17-like cells are also in the skin — location matters.