Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model

Collins, Kelsey H.; Paul, Heather A.; Reimer, Raylene A.; Seerattan, Ruth A.; Hart, David A.; Herzog, Walter

doi:10.1016/j.joca.2015.03.014

Cited by 186 publications

(222 citation statements)

References 47 publications

(46 reference statements)

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“…Gut microbiota were measured using qPCR according to previous methods15. Standard curves for microbial quantification were normalized to 16S rRNA gene copy numbers obtained from the rrnDB34.…”

Section: Methodsmentioning

confidence: 99%

“…Blood serum was collected, prepared, and analyzed for glucose and protein as previously described1536. Five markers were quantified in serum using a custom multiplex assay and Luminex®xMAP technology (Eve Technologies, Calgary, AB; Custom Luminex 5-plex: leptin, insulin, MCP-1, IL-6, TNF-alpha).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the gut microbiota may be a potential link between high-fat high-sucrose (HFS) diet, systemic chronic inflammation, and musculoskeletal integrity151617. For example, diet-dependent microbial products and co-metabolites have been suggested to influence metabolism of host tissues including muscle7.…”

mentioning

confidence: 99%

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A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

Collins

Paul

Hart

et al. 2016

Sci Rep

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The chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

Collins

Paul

Hart

et al. 2016

Sci Rep

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“…Additionally, while the study showed changes in the microbiota associated with prebiotic treatment, how the modifications to the gut microbiome lead to changes in the joint remains to be determined. Another study examined cartilage in rats with diet-induced obesity and found obese animals to have alterations in the composition of articular cartilage (increased Mankin score) as compared to lean animals and that the change in Mankin score was correlated with alterations in the constituents of the gut flora [26]. Although this study did not include frank osteoarthritis, the increase in Mankin score is indicative of changes in cartilage that are present prior to cartilage degradation and, together with the study by Schott and colleagues, suggests that the microbiome may influence osteoarthritis, particularly under conditions of obesity.…”

Section: Osteoarthritismentioning

confidence: 99%

The Microbiome and Bone and Joint Disease

Hernandez

2017

Curr Rheumatol Rep

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Purpose of Review Changes in the constituents and activity of the microbiome have been associated with a number of conditions linked to bone and joint disease. This review concentrates on ways in which the microbiome is known to influence osteoarthritis and osteoporosis. Recent Findings Animal studies have demonstrated that changes in the microbiome can mediate the effects of obesity on cartilage degeneration. Additionally, the microbiome influences the amount of bone (bone quantity), as well as bone tissue material properties (bone quality). Early clinical findings support the effects of the microbiome on osteoporosis and osteoarthritis. Summary Although animal studies implicate the microbiome in the development of bone and joint disease, available results are limited and can be conflicting. Further investigation of the mechanisms leading from changes in the microbiome to alterations in bones and joints are necessary.

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“…The relevance of obesity to dementia development may reside in the low grade inflammation/metabolic syndrome that many obese people exhibit, with excess expression of adipokines that can impact the brain [22,23]. Diet-induced obesity in rats is also reported to impact the brain in rats [24], as well as alter serum adipokine levels [25,26]. Thus, inflammation, as well as other comorbidities, may provide a unique risk for this subset of individuals with obesity to develop dementia.…”

Section: Introductionmentioning

confidence: 99%

Would Adding Low Doses of Lithium Salts and/or Prebiotic Fibre Interventions to an Effective Exercise Protocol Further Enhance Retention of Cognitive Integrity? Potential for Preventing Loss of Cognition with Aging Using Combinations of Low Cost Regimens

Hart¹

2018

JBiSE

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It is clear that loss of cognition is becoming epidemic in our aging society. Onset of dementia and diseases such as Alzheimer's are very prevalent and the prognosis is not optimistic that numbers will decrease in the coming decades. Thus, this epidemic is impacting the quality of life of a large number of people, primarily females, as well as the health care systems of many countries. Of relevance is the fact that large clinical trials of candidate drugs to treat these conditions have not been overwhelming successes, indicating that we may need to take new directions or focus on prevention. One conservative approach in this regard has been the use of exercise protocols to both retain cognition and inhibit progression of loss. With the optimization of exercise protocols, it may be time to step back and ask "how can these successes be augmented to further inhibit risk and stabilize loss early in the development of these conditions?" An example of how this could be approached is via supplementation with low doses of minerals such as lithium salts, or supplementation of the diet with prebiotics in patients with obesity and metabolic syndrome. Regarding the former, recent epidemiological studies have indicated that the content of Li in the drinking water is associated with lower incidences of cognitive diseases/conditions. While not definitive, such clues may warrant performing controlled studies using low doses of lithium salts plus exer- cise to further optimize impact on retention of cognition in those at risk, or those with early disease. Similarly, patients with obesity are at higher risk to develop dementia, and prebiotics can correct some of the metabolic derangements associated with the microbiome in such patients to impact risk. Thus, multiple low cost interventions plus exercise could further enhance retention of cognitive integrity in specific populations.

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Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model

Abstract: 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.

Cited by 186 publications

References 47 publications

A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

The Microbiome and Bone and Joint Disease

Would Adding Low Doses of Lithium Salts and/or Prebiotic Fibre Interventions to an Effective Exercise Protocol Further Enhance Retention of Cognitive Integrity? Potential for Preventing Loss of Cognition with Aging Using Combinations of Low Cost Regimens

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