Gut microbiome shapes the immune system, which in turn regulates bone mass

by Nancy Walsh, Senior Staff Writer, MedPage Today
October 03, 2018

MONTREAL — Probiotic treatment for 12 months led to significant improvements in lumbar spine bone mineral density (BMD) among postmenopausal women, a researcher reported at the annual meeting of the American Society for Bone and Mineral Researchhere.

In a double-blind randomized trial, women who received placebo had significant lumbar spine BMD loss after a year (-0.77%, P=0.0006), whereas those who were given the probiotic therapy experienced no significant loss (-0.17%, P=0.40), according to Claes Ohlsson, MD, PhD, of the University of Gothenberg in Sweden.

“In 2009 we hypothesized that the gut microbiota might influence bone metabolism, because we know that the gut microbiota has the capacity to shape the immune system, and we also know that the immune system can regulate bone mass,” he said. This new research field has been termed osteomicrobiology, “bridging the gap between bone physiology, gastroenterology, immunology, and microbiology,” he explained.

In the subsequent years, a number of rodent studies demonstrated that the gut microbiota could indeed regulate bone mass. For example, in studies of mice raised in a germ-free environment, bone mass was significantly increased but returned to normal mass once the animals were colonized with the conventional gut microbiota. This colonization, he wrote in Trends in Endocrinology and Metabolism, “led to a normalization of both trabecular and cortical bone mass and the frequency of CD4+ T cells and osteoclast precursor cells in bone marrow.”

His group then conducted experiments with estrogen-depleted mice in which three anti-inflammatory strains of Lactobacillus were found to be protective against bone loss.

Subsequently, two small studies showed some limited effects of probiotics in older women. In one study that included 50 patients, the treatment reduced bone resorption markers but had no effect on BMD, while in the second, which included 70 older women with osteopenia, the probiotic treatment alleviated bone loss in the distal tibia but had no effect on the lumbar spine or hip. Both of the studies were underpowered to clearly demonstrate benefits, Ohlsson said.

So he and his colleagues undertook a multicenter, placebo-controlled trial known as the ProBone study that enrolled 234 healthy women in early menopause, with the active treatment consisting of daily capsules containing Lactobacillus paracasei DSM 13434, L. plantarum DSM 15312, and L. plantarum DSM 15313 (the same strains used in the murine studies).

Participants’ mean age was 59, time since menopause was 2 to 12 years, BMI was 24 kg/m², and T scores were above -2.5. Fewer than half of the women were osteopenic at baseline, and none had osteoporosis.

After 12 months, the change in lumbar spine BMD evaluated on DXA was small but statistically significant in the probiotic group, he noted. Adverse events were similar in the probiotic and placebo groups.

The greatest protective effect was seen among women who were less than 6 years postmenopause, whose lumbar spine BMD loss was -0.18% compared with -1.21% in the placebo group (P=0.0001).

There were no changes in BMD at the hip or trochanter, and only slight reductions in bone loss at the femoral neck. “The protective effect seems to be site-specific, and further studies will be needed to determine the mechanism of possible bone site-specific effects,” he said.

“I think our work is unique in that we went from animal studies first published in 2014 to the current results from a large clinical study,” in 2018, he commented.

LAST UPDATED 10.03.2018