K H Collins1, H A Paul2, R A Reimer3, R A Seerattan4, D A Hart5, W Herzog6. 1. Human Performance Laboratory, University of Calgary, AB, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, AB, Canada. Electronic address: khmcolli@ucalgary.ca. 2. Human Performance Laboratory, University of Calgary, AB, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, AB, Canada. Electronic address: haskochy@ucalgary.ca. 3. Human Performance Laboratory, University of Calgary, AB, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, AB, Canada. Electronic address: reimer@ucalgary.ca. 4. Human Performance Laboratory, University of Calgary, AB, Canada. Electronic address: rseerattan@kin.ucalgary.ca. 5. McCaig Institute for Bone and Joint Health, University of Calgary, AB, Canada; The Centre for Hip Health & Mobility, Department of Family Practice, University of British Columbia, Vancouver, BC, Canada. Electronic address: hartd@ucalgary.ca. 6. Human Performance Laboratory, University of Calgary, AB, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, AB, Canada. Electronic address: wherzog@ucalgary.ca.
Abstract
UNLABELLED: Osteoarthritis (OA) may result from intrinsic inflammation related to metabolic disturbance. Obesity-associated inflammation is triggered by lipopolysaccharide (LPS) derived from the gut microbiota. However, the relationship between gut microbiota, LPS, inflammation, and OA remain unclear. OBJECTIVE: To evaluate the associations between gut microbiota, systemic LPS levels, serum and local inflammatory profiles, and joint damage in a high fat/high sucrose diet induced obese rat model. METHODS: 32 rats were randomized to a high fat/high sucrose diet (diet-induced obese (DIO), 40% fat, 45% sucrose, n = 21) or chow diet group (12% fat, 3.7% sucrose n = 11) for 28 weeks. After a 12-week obesity induction period, DIO animals were stratified into Obesity Prone (DIO-P, top 33% by change in body mass, n = 7), and Obesity Resistant groups (DIO-R, bottom 33%, n = 7). At sacrifice, joints were scored using a Modified Mankin Criteria. Blood and synovial fluid analytes, serum LPS, and fecal gut microbiota were analyzed. RESULTS: DIO animals had greater Modified Mankin scores than chow animals (P = 0.002). There was a significant relationship (r = 0.604, p = 0.001) between body fat, but not body mass, and Modified Mankin score. Eighteen synovial fluid and four serum analytes were increased in DIO animals. DIO serum LPS levels were increased compared to chow (P = 0.031). Together, Lactobacillus species (spp.) and Methanobrevibacter spp. abundance had a strong predictive relationship with Modified Mankin Score (r(2) = 0.5, P < 0.001). CONCLUSIONS: Increased OA in DIO animals is associated with greater body fat, not body mass. The link between gut microbiota and adiposity-derived inflammation and metabolic OA warrants further investigation.
UNLABELLED: Osteoarthritis (OA) may result from intrinsic inflammation related to metabolic disturbance. Obesity-associated inflammation is triggered by lipopolysaccharide (LPS) derived from the gut microbiota. However, the relationship between gut microbiota, LPS, inflammation, and OA remain unclear. OBJECTIVE: To evaluate the associations between gut microbiota, systemic LPS levels, serum and local inflammatory profiles, and joint damage in a high fat/high sucrose diet induced obeserat model. METHODS: 32 rats were randomized to a high fat/high sucrose diet (diet-induced obese (DIO), 40% fat, 45% sucrose, n = 21) or chow diet group (12% fat, 3.7% sucrose n = 11) for 28 weeks. After a 12-week obesity induction period, DIO animals were stratified into Obesity Prone (DIO-P, top 33% by change in body mass, n = 7), and Obesity Resistant groups (DIO-R, bottom 33%, n = 7). At sacrifice, joints were scored using a Modified Mankin Criteria. Blood and synovial fluid analytes, serum LPS, and fecal gut microbiota were analyzed. RESULTS: DIO animals had greater Modified Mankin scores than chow animals (P = 0.002). There was a significant relationship (r = 0.604, p = 0.001) between body fat, but not body mass, and Modified Mankin score. Eighteen synovial fluid and four serum analytes were increased in DIO animals. DIO serum LPS levels were increased compared to chow (P = 0.031). Together, Lactobacillus species (spp.) and Methanobrevibacter spp. abundance had a strong predictive relationship with Modified Mankin Score (r(2) = 0.5, P < 0.001). CONCLUSIONS: Increased OA in DIO animals is associated with greater body fat, not body mass. The link between gut microbiota and adiposity-derived inflammation and metabolic OA warrants further investigation.
Keywords:
Gut microbiota and osteoarthritis; Inflammation and osteoarthritis; Metabolic osteoarthritis; Obesity and inflammation; Rat model osteoarthritis
Authors: Eric M Schott; Christopher W Farnsworth; Alex Grier; Jacquelyn A Lillis; Sarah Soniwala; Gregory H Dadourian; Richard D Bell; Madison L Doolittle; David A Villani; Hani Awad; John P Ketz; Fadia Kamal; Cheryl Ackert-Bicknell; John M Ashton; Steven R Gill; Robert A Mooney; Michael J Zuscik Journal: JCI Insight Date: 2018-04-19
Authors: Kelsey H Collins; Walter Herzog; Raylene A Reimer; Carol R Reno; Bryan J Heard; David A Hart Journal: Inflamm Res Date: 2017-10-26 Impact factor: 4.575
Authors: Kelsey H Collins; Kristin L Lenz; Eleanor N Pollitt; Daniel Ferguson; Irina Hutson; Luke E Springer; Arin K Oestreich; Ruhang Tang; Yun-Rak Choi; Gretchen A Meyer; Steven L Teitelbaum; Christine T N Pham; Charles A Harris; Farshid Guilak Journal: Proc Natl Acad Sci U S A Date: 2021-01-05 Impact factor: 11.205