The causal role of gut microbiota in development of osteoarthritis

Yu, Xinghao; Yang, Yuan; Cao, Rong-Rong; Bo, Lin; Lei, Shu‐Feng

doi:10.1016/j.joca.2021.08.003

Cited by 116 publications

(79 citation statements)

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“…19 studies were included in the final analysis, of which 10 were on animal models [ 31 – 38 ], 8 were human clinical or ex vivo studies [ 5 , 18 , 19 , 38 – 47 ], and one was based on analysis of publicly available databases [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…Finally, they presented evidence that this association was driven by local inflammation (synovitis and joint effusion) in the joint assessed through a subgroup MRI analysis in 373 patients. Interestingly, a recent study looking a publicly available sequencing data, used mendelian randomization approach to identify microbial taxa associated to OA in humans [ 40 ]. Their finding were in agreement with what previously reported.…”

Section: Resultsmentioning

confidence: 99%

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The relation between the gut microbiome and osteoarthritis: A systematic review of literature

et al. 2021

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Background Along with mechanical and genetic factors, emerging evidence suggests that the presence of low-grade inflammation has a role in the pathogenesis of osteoarthritis (OA) and seems to be related to the microbiome composition of the gut. Purpose To provide evidence whether there is clinical or preclinical evidence of gut-joint axis in the pathogenesis and symptoms of OA. Methods An extensive review of the current literature was performed using three different databases. Human, as well as animal studies, were included. The risk of bias was identified using ROBINS and SYRCLE tools, while the quality of evidence was assessed using GRADE and CAMADARES criteria. Results A total of nineteen articles were included. Multiple animal studies demonstrated that both obesity, and high-fat and high-sugar diets resulted in a gut dysbiosis status characterized by increased Firmicutes/Bacteroidetes (F/B) phyla ratio and increased permeability. These changes were associated with increased lipopolysaccharide serum levels, which consequently resulted in synovitis and OA severity. The administration of pre-and probiotics partially reversed this bacterial composition. In addition, in human studies, a decreased amount of gut Bacteroidetes, subsequent increased F/B ratio, have also been observed in OA patients. Conclusions Our review confirms preliminary yet sound evidence supporting a gut-joint axis in OA in primarily preclinical models, by showing an association between diet, gut dysbiosis and OA radiological severity and self-reported symptoms. Clinical studies are needed to confirm these findings, and to investigate whether interventions targeting the composition of the microbiome will have a beneficial clinical effect.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The relation between the gut microbiome and osteoarthritis: A systematic review of literature

et al. 2021

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“…Methanogens , the producers of methane, can inhibit intestinal transit and contractile activity ( Pimentel et al, 2006 ). Several studies have verified a positive association between the increased prevalence of Methanogens such as Methanosphaera and Methanobacteriaceae in the gut with intestinal inflammation and inflammatory bowel diseases ( Lecours et al, 2014 ; Yu et al, 2021 ). Clostridium methylpentosum may conduce to the gut microbiota dysbiosis-associated changes of the host during infection ( Do-Nascimento et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of glucose oxidase on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli

et al. 2022

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Glucose oxidase (GOD) could benefit intestinal health and growth performance in animals. However, it is unknown whether GOD can protect piglets against bacterial challenge. This study aimed to evaluate the protective effects of GOD on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli (ETEC). A total of 44 male weaned piglets around 38 days old were divided into four groups (11 replicates/group): negative control (NC), positive control (PC), CS group (PC piglets +40 g/t colistin sulfate), and GOD group (PC piglets +200 g/t GOD). All piglets except those in NC were challenged with ETEC (E. coli K88) on the 11th day of the experiment. Parameter analysis was performed on the 21st day of the experiment. The results showed that the ETEC challenge elevated (p < 0.05) the rectal temperature and fecal score of piglets at certain time-points post-challenge, reduced (p < 0.05) serum glucose and IgG levels but increased (p < 0.05) serum alanine aminotransferase activity, as well as caused (p < 0.05) intestinal morphology impairment and inflammation. Supplemental GOD could replace CS to reverse (p < 0.05) the above changes and tended to increase (p = 0.099) average daily gain during the ETEC challenge. Besides, GOD addition reversed ETEC-induced losses (p < 0.05) in several beneficial bacteria (e.g., Lactobacillus salivarius) along with increases (p < 0.05) in certain harmful bacteria (e.g., Enterobacteriaceae and Escherichia/Shigella). Functional prediction of gut microbiota revealed that ETEC-induced upregulations (p < 0.05) of certain pathogenicity-related pathways (e.g., bacterial invasion of epithelial cells and shigellosis) were blocked by GOD addition, which also normalized the observed downregulations (p < 0.05) of bacterial pathways related to the metabolism of sugars, functional amino acids, nucleobases, and bile acids in challenged piglets. Collectively, GOD could be used as a potential antibiotic alternative to improve growth and serum parameters, as well as attenuate clinical symptoms and intestinal disruption in ETEC-challenged piglets, which could be associated with its ability to mitigate gut microbiota dysbiosis. Our findings provided evidence for the usage of GOD as an approach to restrict ETEC infection in pigs.

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“…An extension to MR that is becoming more popular in the musculoskeletal field is multivariable MR. (1,4,40,(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75) When evidence of pleiotropy is observed, and there is a trait believed to explain the pleiotropy, multivariable MR can estimate the direct effect of the exposure on the outcome, independent of the additional trait. (76,77) For example, in our recent analysis, we used multivariable MR to identify a BMI-independent effect of BMD on OA, as we suspected that the pleiotropy we observed in our univariable analyses reflected pleiotropy via the shared causal factor, BMI.…”

Section: Multivariable and Two-step Mrmentioning

confidence: 99%

A Guide for Understanding and Designing Mendelian Randomization Studies in the Musculoskeletal Field

et al. 2022

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Mendelian randomization (MR) is an increasingly popular component of an epidemiologist's toolkit, used to provide evidence of a causal effect of one trait (an exposure, eg, body mass index [BMI]) on an outcome trait or disease (eg, osteoarthritis). Identifying these effects is important for understanding disease etiology and potentially identifying targets for therapeutic intervention. MR uses genetic variants as instrumental variables for the exposure, which should not be influenced by the outcome or confounding variables, overcoming key limitations of traditional epidemiological analyses. For MR to generate a valid estimate of effect, key assumptions must be met. In recent years, there has been a rapid rise in MR methods that aim to test, or are robust to violations of, these assumptions. In this review, we provide an overview of MR for a non-expert audience, including an explanation of these key assumptions and how they are often tested, to aid a better reading and understanding of the MR literature. We highlight some of these new methods and how they can be useful for specific methodological challenges in the musculoskeletal field, including for conditions or traits that share underlying biological pathways, such as bone and joint disease.

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The causal role of gut microbiota in development of osteoarthritis

Cited by 116 publications

References 50 publications

The relation between the gut microbiome and osteoarthritis: A systematic review of literature

The relation between the gut microbiome and osteoarthritis: A systematic review of literature

Effects of glucose oxidase on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli

A Guide for Understanding and Designing Mendelian Randomization Studies in the Musculoskeletal Field

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