Alterations to the gut microbiome impair bone tissue strength in aged mice

Authors: MACY, CASTENADA - Cornell University; SMITH, KELSEY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; NIXON, JACOB - Cornell University; HERNANDEZ, CHRISTOPHER - Cornell University; ROWAN, SHELDON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Bone Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2021
Publication Date: 4/8/2021
Citation: Macy, C., Smith, K.M., Nixon, J.C., Hernandez, C.J., Rowan, S. 2021. Alterations to the gut microbiome impair bone tissue strength in aged mice. Bone Reports. 14:101065. https://doi.org/10.1016/j.bonr.2021.101065.
DOI: https://doi.org/10.1016/j.bonr.2021.101065

Interpretive Summary: As our population becomes older, the number of people living with age-related bone loss and fragility, known as osteoporosis, continues to increase. Osteoporosis leads to an increased risk of bone fracture, which can lead to hospitalization and permanent disability or death. Recent research has discovered that the bacteria and other microorganisms living in the gut, known as the gut microbiome, may modify the risk of osteoporosis, but it is not yet known if changes to the microbiome later in life can prevent bone disease. We tested this by feeding 12-month old mice (equivalent to middle age) different diets, some of which contained antibiotics to kill many kinds of beneficial gut bacteria. After an additional year of feeding, we analyzed bones to determine their shape and strength and we collected feces to measure gut bacteria. We found that gut microbiomes changed by diet and by antibiotic treatment. Mice given antibiotics had few beneficial bacteria, but expansion of potentially harmful antibiotic resistant bacteria. Antibiotic treatment also led to decreased whole bone strength - a problem related to bone tissue quality. This is, to our knowledge, the first published research showing that modifying the gut microbiome later in life can affect bone tissue properties and strength. Modifying the microbiome to promote bone health is a new intervention strategy currently being explored, and our results promisingly show that a microbiome intervention may still be effective, even in older adults.

Technical Abstract: Whole bone strength and resistance to fracture are determined by a combination of bone quantity and bone quality - key factors in determining risk for osteoporosis and age-related fractures. Recent preclinical studies have shown that alterations to the gut microbiome can influence bone quantity as well as bone tissue quality. Prior work on the gut microbiome and bone has been limited to young animals, and it is unknown if the gut microbiome can alter bone tissue strength in aged animals. Here we ask if alterations to the constituents of the gut microbiome influence bone strength in older mice (12-24 months of age). Male C57BL/6J mice raised on a standard chow diet until 12 months of age were assigned to one of three diets: high glycemic, low glycemic, or low glycemic diet containing antibiotics (ampicillin and neomycin) to modify the constituents of the gut microbiome. The group fed the low glycemic diet containing antibiotics showed reductions in whole bone strength that could not be explained by geometry, indicating reduced bone tissue strength (p < 0.007). The high glycemic diet group had larger bone cross-sectional area and moment of inertia and a corresponding greater bone strength as compared to the low glycemic groups, however tissue strength did not noticeably differ from that of the low glycemic group. These findings demonstrate that modifying the gut microbiome in aged mice can alter bone tissue quality.