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.

Public Health Relevance

The proposed work examines osteoporosis. Micro-organisms in the gut have been linked to many of the potential causes of osteoporosis (low peak bone mass, bone loss at menopause, etc.) but very little is known about how organisms in the gut might influence bone mass and strength. A better understanding of the relationship between microorganisms in the gut and bone has the potential to lead to probiotic treatments for osteoporosis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Research Service Awards for Senior Fellows (F33)
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Special Emphasis Panel (ZRG1-F10B-S (20))
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Sharrock, William J
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Cornell University
Engineering (All Types)
Schools of Engineering
United States
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Guss, Jason D; Horsfield, Michael W; Fontenele, Fernanda F et al. (2017) Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties. J Bone Miner Res 32:1343-1353
Hernandez, Christopher J; Guss, Jason D; Luna, Marysol et al. (2016) Links Between the Microbiome and Bone. J Bone Miner Res 31:1638-46
Sun, Xuanhao; Weinlandt, William D; Patel, Harsh et al. (2014) A microfluidic platform for profiling biomechanical properties of bacteria. Lab Chip 14:2491-8