Antibiotic disruption of the gut microbiome dysregulates skeletal health.
The gut is colonized by diverse microorganisms that form a microbial community known as the gut microbiota. Research suggests that gut microbiota immunomodulatory effects influence pathologic conditions centered in the gut, and distant anatomical sites such as the liver, brain, heart, and skeleton. Now, a study from researchers at the University of South Carolina shows that antibiotic disruption of the gut microbiota induced a pro-inflammatory response which led to increased activity of osteoclasts, cells which degrade and resorp bone. The team state their data introduces antibiotics as a critical modulator of gut microbiota osteoimmune response during post-pubertal skeletal development. The opensource study is published in the journal American Journal of Pathology.
Previous studies show that the post-pubertal phase of development is a critical window which supports the accrual of approximately 40% of a person’s peak bone-mass with work showing that the gut microbiota also contributes to skeletal health. Antibiotic perturbation of the normal gut microbiota during postnatal skeletal development has been shown to influence bone mass and its mechanical properties as well, yet the osteoimmune mechanisms linking antibiotic effects and the gut microbiota on skeletogenesis are unknown. The current study investigates the impact of disrupting the healthy gut microbiome with antibiotics on post-pubertal skeletal development.
The current study treats mice with a cocktail of three antibiotics to determine the impact of antibiotics on the gut microbiota in post-pubertal skeletal development. Results show that antibiotic treatment led to major alterations in the gut microbiota, resulting in specific changes to large groups of bacteria. Data findings show that antibiotic-induced changes in the microbiota had little impact on cortical bone; however, there were significant changes to the trabecular bone, the type of bone which undergoes high rates of bone metabolism.
The group explain that bone metabolism is controlled through a balance of bone-resorbing, osteoclast, and bone-building, osteoblast, cells. They go on to add they observed there were no changes to the osteoblasts, while osteoclast cell number, size and activity were increased. Results show that levels of pro-osteoclastic signaling molecules were increased in the circulation of antibiotic-treated animals, suggesting that increased osteoclast activity is the result of a specific immune response to a change in the microbiota. Examination of immune cell populations in the bone marrow revealed a significant increase in myeloid-derived suppressor cells (MDSCs) of antibiotic-treated animals, MDSCs are known to regulate the innate and adaptive immune response during various diseases. To conclude, antigen presentation and processing were suppressed in the bone marrow upon antibiotic treatment.
The team surmise their data shows that antibiotic disruption of the gut microbiota dysregulates communication between immune cells and bone cells, leading to disruption of skeletal development. For the future, the researchers state studies will incorporate an antibiotic regimen to better translate human antibiotic treatments, which in turn could lead to clinical trials aimed at defining the impact of specific antibiotics on the gut microbiome.