Associations between gut microbiota, flagellin production and bone microstructure

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DESCRIPTION (provided by applicant): The proposed work examines interactions between gut microbiota and bone. Early evidence suggests that the composition and function of the gut microbiota is correlated with most of the factors leading to the development of osteoporosis. This senior fellowship has two goals: the training goal is to provide the senior fellow with expertise in the study of the gut microbiome and experimental methods used to manipulate and examine the gut microbiome which he plans to apply to conditions of bone loss in the post-award period. The research objective is to test the hypothesis that alterations in gut microbiota associated with toll-like receptor 5 (TLR5) deficiency lead to reductions in bone mass. Chronic inflammation in the gut as seen in inflammatory bowel results in bone loss. TLR5 deficient mice display low level chronic inflammation in the gut as a result of changes in gut microbiota, but it s not known if TLR5 deficient mice also experience alterations in bone. Bone mass will be examined in the axial and appendicular skeleton of TLR5 deficient mice, wild type and in wild type mice receiving a transplant of gut microbiota from TLR5 deficient mice (a process known to transplant the state of chronic inflammation in the gut). The proposed work will provide the senior fellow with training in the use of a germ free facility, including transplantation of gut microbiota and analysis of the composition of the gut flora for future studies in bone.