Evidence is mounting that the microbes residing in the human gut play a role in a range of physiologic functions, including immunity, metabolism, inflammation, and even mental health.

A new study led by Harvard Medical School researchers at Hebrew SeniorLife links the gut microbiome to yet another important aspect of human health: bone density and strength. The research, published August 2023 in Frontiers of Endocrinology, identified tantalizing links between certain bacteria and critical dimensions of bone health.

“We found patterns in which greater abundance of microbiota were associated with worse measures of bone density and microarchitecture,” said principal investigator Douglas Kiel, HMS professor of medicine and senior scientist at the Marcus Institute for Aging Research at Hebrew SeniorLife.

The researchers caution that the findings are only associations and do not demonstrate cause and effect. However, the findings do suggest that gut microbes modulate the strength, density, and composition of bones in indirect, yet powerful, ways.

Low bone density, along with deterioration of the internal structure, or microarchitecture, of bones, are factors that can increase the risk of developing osteoporosis.

“Some bacteria can lead to low levels of inflammation that may affect bone health.”

The research is believed to be the largest observational study to date exploring the possible link between gut bacteria and skeletal health using high-resolution imaging in men and women across a wide age range.

Researchers analyzed data from participants in two large studies: the Framingham Heart Study, which included 1,227 men and women of diverse ages, and the Osteoporosis in Men Study, which included 836 older men. High-resolution scans of the forearm and shin bones provided information on bone density, microarchitecture, and strength, while gene sequencing of stool samples offered insight into gut microbial makeup.

The researchers pinpointed dozens of bacterial classes associated with skeletal health measures. For example, they noted negative associations between the abundance of bacteria called Akkermansia and Clostridiales bacterium DTU089 with bone health as measured by bone density and bone composition. Previous studies had linked Akkermansia with obesity and DTU089 with lower physical activity and lower protein intake — which in turn are characteristics associated with worse skeletal health.

Interestingly, a greater number of bacterial types appeared negatively associated with bone density but positively associated with bone size. The researchers said this finding could indicate that certain microbes influence bone growth at the expense of bone density as a person ages.

The researchers caution that the study doesn’t prove that gut microbes directly lead to stronger or weaker bones. Nonetheless, the findings should provoke further investigation into the ways bacteria might influence skeletal health.

“Some bacteria can lead to low levels of inflammation that may affect bone health,” said Kiel. “Ultimately, if findings like this are confirmed, we may be able to target the gut microbiome to influence skeletal health.”

Authorship, funding, disclosures

Additional authors on the paper include Paul Okoro, Eric Orwoll, Curtis Huttenhower, Xochitl Morgan, Thomas Kuntz, Lauren McIver, Alyssa Dufour, Mary Bouxsein, Lisa Langsetmo, Samaneh Farsijani, Deborah Kado, Roberto Pacifici, and Shivani Sahni.

This study was supported by the National Institutes of Health (grants U01AG027810, U01AG042124, U01AG042139, U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, R01AG066671, UL1TR002369, and R01AR061445). The work was also funded by the National Heart, Lung, and Blood Institute’s Framingham Heart Study (HHSN268201500001I, N01-HC 25195, and R01HL131015). For a complete list of funding sources, please refer to the paper.

Orwoll consults for Amgen, Bayer, BioCon, and Radius and has received research support from Mereo and travel funding from the OI Foundation. Kiel has received grants to his institution from Amgen, Inc., and Radius Health, as well as consulting fees from Solarea Bio, Radius Health, and Pfizer for serving on scientific advisory boards, fees from Agnovos for serving on a data and safety monitoring committee, and royalties for publication in UpToDate by Wolters Kluwer. Sahni reports institutional grants from Dairy Management Inc. (ended September 2022) and Solarea Bio Inc. (ended March 2022) and has reviewed grants for the American Egg Board’s Egg Nutrition Center and National Dairy Council. Kado reports consulting fees from Amgen and Ultragenyx for serving on scientific advisory boards, royalties for publication in UpToDate by Wolters Kluwer, as well as grant funding from Starkey.

Adapted from a Hebrew SeniorLife news release and originally published in Harvard Medical School News.