Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis.

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.

Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia.

PURPOSE: Probiotics, as live microorganisms that improve intestinal microbial balance, have been implicated in the modulation of neurodegenerative diseases via the microbiome-gut-brain axis by improving gut dysbiosis. This review examines the association between probiotics and neurocognitive function in age-related dementia. METHODS: We searched MEDLINE, Embase, Scopus, Web of Science and Cochrane library for in vivo studies using equivalent combinations of "probiotics" and "dementia" as per PRISMA. From the 52 in vivo studies identified, 5 human and 22 animal studies with comparable quantitative outcomes on neurocognitive/behavioural function were meta-analysed by forest plots, subgroup analysis and meta-regression. The analysis of biomarkers, risk of bias and publication bias were also performed. RESULTS: In elderly humans, probiotics correlates with a non-significant difference of neurocognitive function in Mini-Mental State Examination, but with significant improvement only in those diagnosed with Alzheimer's disease. In animals, probiotics significantly improved neurocognitive function as measured by Morris Water Maze, Y-Maze, and Passive Avoidance. Further analysis by subgrouping and meta-regression found that the probiotics-neurodegeneration association is age dependent in humans but is neither dose dependent nor duration dependent in animals or humans. Analysis of biomarkers suggested that the neurocognitive effect of probiotics is associated with an altered gut microbiome profile, downregulated proteinopathic, inflammatory and autophagic pathways, and upregulated anti-oxidative, neurotrophic, and cholinergic pathways. CONCLUSION: Overall, we report promising results in animal studies but limited evidence of probiotics leading to neurocognitive improvement in humans. More research into probiotics should be conducted, especially on live biotherapeutic products for targeted treatment of gut dysbiosis and age-related dementia.