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

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.

The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis

“…Diet modification and exercise are among the two most beneficial and conservative treatment approaches. Studies in rodents show promising results for the addition of high-fiber diets and the resultant increase in the gut microbiome production of short-chain fatty acids (SCFA), particularly butyrate [14], the primary metabolites of microbial fermentation in the gut [29]. SCFAs appear to protect against postmenopausal and inflammatory bone loss, repair intestinal barriers, and prevent the development of osteoporosis in mice [30][31][32].…”

“…Based on the abundance of metabolite and cell signaling molecules, particularly short-chain fatty acids such as butyrate [13], produced by the gut microbiota, it stands to reason that these states of unbalance may be connected and should be investigated. Furthermore, preclinical animal models have shown that alterations in the gut microbiota can decrease the quality and hence the strength of bone tissue [14], and in germ-free mice (i.e., mice without a gut microbiota), the number of osteoclasts was reduced, leading to increased bone mass [15].…”

Altered gut microbiota and metabolites profile are associated with reduced bone metabolism in ethanol‐induced osteoporosis

“… 39 Previous studies have shown that the bone strength is not affected by long‐term low‐glycemic diet containing antibiotics, but GM is significantly changed. 40 Here, we report that the bacterial community richness and evenness are lower in the faecal samples from ethanol and antibiotics treated rats using the Chao1 estimator. Moreover, the differences in bacterial community structure are further investigated by PCoA and ANOSIM, indicating the differences in the structure and composition of GM among groups, which highlights the induction of GM dysbiosis in chronic heavy ethanol consumption.…”

“…Meanwhile, antibiotics are applied in rats for 16 weeks as a GM dysbiosis matched group, which has been proven to reduce taxonomic richness and diversity and influence the abundance of bacterial taxa in faeces 39 . Previous studies have shown that the bone strength is not affected by long‐term low‐glycemic diet containing antibiotics, but GM is significantly changed 40 . Here, we report that the bacterial community richness and evenness are lower in the faecal samples from ethanol and antibiotics treated rats using the Chao1 estimator.…”

Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis

“…Bone is impacted by gut microbial dysbiosis that both impairs the intestinal absorption of calcium and dysregulates osteoclasts’ activity via the serum levels of insulin-like growth factor 1 (IGF-1) [ 17 ]. Moreover, microbiota alterations also reduce bone strength and quality [ 18 , 19 ], and affect the OPG/RANKL pathway in osteoclasts [ 20 ]. Furthermore, dysbiosis in mice also interferes with skeletal muscle mass and physical performance, altering the production of rapsyn and Lrp4—two crucial proteins in the functioning of neuromuscular junctions [ 21 ].…”