The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

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Gut Microbiome: Profound Implications for Diet and Disease

Osteoarthritis (OA) is the most frequent form of arthritis and a leading cause of pain and disability worldwide. OA can affect any synovial joint, although the hip, knee, hand, foot and spine are the most commonly affected sites. Knowledge about the occurrence and risk factors for OA is important to define the clinical and public health burden of the disease to understand mechanisms of disease occurrence and may also help to inform the development of population-wide prevention strategies. In this article, we review the occurrence and risk factors for OA and also consider patient-reported outcome measures that have been used for the assessment of the disease.

Update on the epidemiology, risk factors and disease outcomes of osteoarthritis

We live in a world with an ever-increasing ageing population. Studying healthy ageing and reducing the socioeconomic impact of age-related diseases is a key research priority for the industrialised and developing countries, along with a better mechanistic understanding of the physiology and pathophysiology of ageing that occurs in a number of age-related musculoskeletal disorders. Arthritis and musculoskeletal disorders constitute a major cause of disability and morbidity globally and result in enormous costs for our health and social-care systems. By gaining a better understanding of healthy musculoskeletal ageing and the risk factors associated with premature ageing and senescence, we can provide better care and develop new and better-targeted therapies for common musculoskeletal disorders. This review is the outcome of a two-day multidisciplinary, international workshop sponsored by the Institute of Advanced Studies entitled “Musculoskeletal Health in the 21st Century” and held at the University of Surrey from 30th June-1st July 2015. The aim of this narrative review is to summarise current knowledge of musculoskeletal health, ageing and disease and highlight strategies for prevention and reducing the impact of common musculoskeletal diseases.

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Strategies for optimising musculoskeletal health in the 21st century.

Osteoarthritis is a complex joint disease in which all involved tissues play an important role in its onset and progression. It has been suggested that osteoarthritis is likely to be a systemic disease involving stromal cell differentiation and lipid metabolism while altered lipid metabolism has been implicated as a critical player in its pathogenesis. As excessive accumulation of free cholesterol is toxic for the cells, the accumulation of lipids in chondrocytes may signify a causal relationship to development and/or progression of osteoarthritis; therefore we investigated the expression of genes regulating reverse cholesterol transport, as ABCA1, ApoA1, LXRa, LXR_, in human osteoarthritic chondrocytes. We also investigated the effect of an LXR agonist on ABCA1 and ApoA1 expression and, for the first time, on cholesterol effiux and lipid accumulation in osteoarthritic chondrocytes. Articular cartilage samples were obtained from femoral condyles and tibial plateaus of patients with primary OA undergoing knee replacement surgery while normal cartilage was obtained from eight individuals undergoing fracture repair surgery, with no history of joint disease. Total cellular RNA was extracted from all samples and ABCA1, ApoA1, and LXRα and LXRβ mRNA and protein expression levels were evaluated using real-time PCR and Western blot analysis respectively. The effect of the synthetic LXR agonist TO-901317 was studied after treatment of osteoarthritic chondrocytes and subsequent investigation of ABCA1 and ApoA1 mRNA expression levels. Cholesterol effiux was evaluated in osteoarthritic chondrocytes radiolabeled with [1,2(n)-3H] cholesterol after LXR treatment, while intracellular lipid accumulation was studied after Oil-red-O staining. ApoA1 and ABCA1 mRNA levels were significantly lower in osteoarthritic cartilage compared to normal (p Our findings suggest that impaired expression of genes regulating cholesterol effiux may be a critical player in osteoarthritis, while the ability of the LXR agonist to facilitate cholesterol effiux suggests that it may be a target for therapeutic intervention in osteoarthritis.

Impaired expression of genes regulating cholesterol efflux in human osteoarthritic chondrocytes

Epidemiology of osteoarthritis

As current treatment options in OA are very limited, OA patients would benefit greatly from some ability to self-manage their condition. Since diet may potentially affect OA, we reviewed the literature on the relationship between nutrition and OA risk or progression, aiming to provide guidance for clinicians. For overweight/obese patients, weight reduction, ideally incorporating exercise, is paramount. The association between metabolic syndrome, type-2 diabetes and OA risk or progression may partly explain the apparent benefit of dietary-lipid modification resulting from increased consumption of long-chain omega-3 fatty-acids from oily fish/fish oil supplements. A strong association between OA and raised serum cholesterol together with clinical effects in statin users suggests a potential benefit of reduction of cholesterol by dietary means. Patients should ensure that they meet the recommended intakes for micronutrients such as vitamin K, which has a role in bone/cartilage mineralization. Evidence for a role of vitamin D supplementation in OA is unconvincing.

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Heather Browne

Papers

What is the evidence for a role for diet and nutrition in osteoarthritis