Dataset Information

Modifiable Host Factors in Melanoma: Emerging Evidence for Obesity, Diet, Exercise, and the Microbiome.

ABSTRACT: PURPOSE OF REVIEW:We discuss how potentially modifiable factors including obesity, the microbiome, diet, and exercise may impact melanoma development, progression, and therapeutic response. RECENT FINDINGS:Obesity is unexpectedly associated with improved outcomes with immune and targeted therapy in melanoma, with early mechanistic data suggesting leptin as one mediator. The gut microbiome is both a biomarker of response to immunotherapy and a potential target. As diet is a major determinant of the gut microbiome, ongoing studies are examining the interaction between diet, the gut microbiome, and immunity. Data are emerging for a potential role of exercise in reducing hypoxia and enhancing anti-tumor immunity, though this has not yet been well-studied in the context of contemporary therapies. Recent data suggests energy balance may play a role in the outcomes of metastatic melanoma. Further studies are needed to demonstrate mechanism and causality as well as the feasibility of targeting these factors.

SUBMITTER: Warner AB

PROVIDER: S-EPMC7472428 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Modifiable Host Factors in Melanoma: Emerging Evidence for Obesity, Diet, Exercise, and the Microbiome.

Warner Allison Betof AB McQuade Jennifer L JL

Current oncology reports 20190701 8

<h4>Purpose of review</h4>We discuss how potentially modifiable factors including obesity, the microbiome, diet, and exercise may impact melanoma development, progression, and therapeutic response.<h4>Recent findings</h4>Obesity is unexpectedly associated with improved outcomes with immune and targeted therapy in melanoma, with early mechanistic data suggesting leptin as one mediator. The gut microbiome is both a biomarker of response to immunotherapy and a potential target. As diet is a major d ...[more]

PMID: 31263961

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Project description:AbstractBackgroundThe potential modifiable factors influencing irritable bowel syndrome (IBS) have not been thoroughly documented. We aimed to systematically investigate the modifiable factors associated with IBS, while accounting for the impact of unobserved confounders and coexisting disorders.MethodsGenetic correlation and Mendelian randomisation (MR) analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS. Subsequently, multiresponse MR (MR2) was employed to further examine these associations. Summary-level genome-wide association data were used. Modifiable factors and coexisting disorders (ie, gastrointestinal and psychiatric disorders) were identified based on evidence from cohort studies and meta-analysis. In all analyses, IBS was the primary outcome, while in the MR2 analysis, coexisting disorders were also treated as outcomes alongside IBS.ResultsMost identified modifiable factors and coexisting disorders exhibited genetic correlations with IBS. MR analyses revealed strong causation between IBS and multisite chronic pain (OR=2.20, 95% CI 1.82 to 2.66), gastro-oesophageal reflux disease (OR=1.31, 95% CI 1.23 to 1.39), well-being spectrum (OR=0.17, 95% CI 0.13 to 0.21), life satisfaction (OR=0.31, 95% CI 0.25 to 0.38), positive affect (OR=0.30, 95% CI 0.24 to 0.37), neuroticism score (OR=1.20, 95% CI 1.16 to 1.25) and depression (OR=1.50, 95% CI 1.37 to 1.66). Additionally, smoking, alcohol frequency, college or university degree, intelligence, childhood maltreatment, frailty index, diverticular disease of the intestine and schizophrenia were suggestively associated with IBS. Robust associations were found between multisite chronic pain and both IBS and coexisting disorders.ConclusionsOur study identified a comprehensive array of potential modifiable factors and coexisting disorders associated with IBS, supported by genetic evidence, including genetic correlation and multiple MR analyses. The presence of multisite chronic pain may offer a promising avenue for the concurrent prevention of IBS and its coexisting disorders.

Project description:BackgroundCurrent paradigms for predicting weight loss in response to energy restriction have general validity but a subset of individuals fail to respond adequately despite documented diet adherence. Patients in the bottom 20% for rate of weight loss following a hypocaloric diet (diet-resistant) have been found to have less type I muscle fibres and lower skeletal muscle mitochondrial function, leading to the hypothesis that physical exercise may be an effective treatment when diet alone is inadequate. In this study, we aimed to assess the efficacy of exercise training on mitochondrial function in women with obesity with a documented history of minimal diet-induced weight loss.MethodsFrom over 5000 patient records, 228 files were reviewed to identify baseline characteristics of weight loss response from women with obesity who were previously classified in the top or bottom 20% quintiles based on rate of weight loss in the first 6 weeks during which a 900 kcal/day meal replacement was consumed. A subset of 20 women with obesity were identified based on diet-resistance (n=10) and diet sensitivity (n=10) to undergo a 6-week supervised, progressive, combined aerobic and resistance exercise intervention.FindingsDiet-sensitive women had lower baseline adiposity, higher fasting insulin and triglycerides, and a greater number of ATP-III criteria for metabolic syndrome. Conversely in diet-resistant women, the exercise intervention improved body composition, skeletal muscle mitochondrial content and metabolism, with minimal effects in diet-sensitive women. In-depth analyses of muscle metabolomes revealed distinct group- and intervention- differences, including lower serine-associated sphingolipid synthesis in diet-resistant women following exercise training.InterpretationExercise preferentially enhances skeletal muscle metabolism and improves body composition in women with a history of minimal diet-induced weight loss. These clinical and metabolic mechanism insights move the field towards better personalised approaches for the treatment of distinct obesity phenotypes.FundingCanadian Institutes of Health Research (CIHR-INMD and FDN-143278; CAN-163902; CIHR PJT-148634).

Dataset Information

Modifiable Host Factors in Melanoma: Emerging Evidence for Obesity, Diet, Exercise, and the Microbiome.

Publications

Modifiable Host Factors in Melanoma: Emerging Evidence for Obesity, Diet, Exercise, and the Microbiome.

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