Search

Author(s): Francesco Asnicar [sup.1] , Sarah E. Berry [sup.2] , Ana M. Valdes [sup.3] [sup.4] , Long H. Nguyen [sup.5] , Gianmarco Piccinno [sup.1] , David A. Drew [sup.5] , [...], The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease. Analyses from the gut microbiome of over 1,000 individuals from the PREDICT 1 study, for which detailed long-term diet information as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements are available, unveil new associations between specific gut microbes, dietary habits and cardiometabolic health.

Diet is a modifiable risk factor for common chronic diseases and mental health disorders, and its effects are under partial genetic control. To estimate the impact of diet on individual health, most epidemiological and genetic studies have focused on individual aspects of dietary intake. However, analysing individual food groups in isolation does not capture the complexity of the whole diet pattern. Dietary indices enable a holistic estimation of diet and account for the intercorrelations between food and nutrients. In this study we performed the first ever genome-wide association study (GWA) including 173,701 individuals from the UK Biobank to identify genetic variants associated with the Dietary Approaches to Stop Hypertension (DASH) diet. DASH was calculated using the 24 h-recall questionnaire collected by UK Biobank. The GWA was performed using a linear mixed model implemented in BOLT-LMM. We identified seven independent single-nucleotide polymorphisms (SNPs) associated with DASH. Significant genetic correlations were observed between DASH and several educational traits with a significant enrichment for genes involved in the AMP-dependent protein kinase (AMPK) activation that controls the appetite by regulating the signalling in the hypothalamus. The colocalization analysis implicates genes involved in body mass index (BMI)/obesity and neuroticism (ARPP21, RP11-62H7.2, MFHAS1, RHEBL1). The Mendelian randomisation analysis suggested that increased DASH score, which reflect a healthy diet style, is causal of lower glucose, and insulin levels. These findings further our knowledge of the pathways underlying the relationship between diet and health outcomes. They may have significant implications for global public health and provide future dietary recommendations for the prevention of common chronic diseases. [ABSTRACT FROM AUTHOR]

Background: The Dietary Approaches to Stop Hypertension (DASH) diet is beneficial in reducing blood pressure; however, this may be a consequence of concurrent weight reduction. In the present study, we investigated whether body mass index (BMI) mediates the association between the DASH diet and hypertension and investigate common metabolic pathways. Methods: We included 2424 females from the cross‐sectional TwinsUK cohort, with blood pressure, BMI and dietary intake measured within 1.01 (SD = 0.68) years and serum metabolomics profiling (591 metabolites). We constructed a mediation model to test the mediation effects of BMI on the total effect of the DASH diet on hypertension. To identify a metabolite panel associated with the DASH diet and BMI, we built random forest models for each trait, and selected the common metabolic contributors using five‐fold cross‐validation error. Results: We found that BMI fully mediates the association between the DASH diet and hypertension, explaining 39.1% of the variance in hypertension. We then identified a panel of six common metabolites predicting both the DASH diet and BMI with opposing effects. Interestingly, at the univariate level, the metabolites were also associated with hypertension in the same direction as BMI. The strongest feature, 1‐nonadecanoyl‐GPC (19:0), was positively associated with the DASH diet (β [SE] = 0.65 [0.12]) and negatively with BMI (β [SE] = −1.34 [0.12]) and hypertension (odds ratio = 0.71, 95% confidence interval = 0.6–0.84). Conclusions: We highlight the role of BMI in the mechanisms by which the DASH diet influences hypertension and also highlight common metabolic pathways. Further studies should investigate the underlying molecular mechanisms to increase our understanding of the beneficial ways of treating hypertension. Key points: Adherence to the DASH diet can reduce blood pressure; however, this may be a consequence of concurrent weight reduction.In a large sample of 2424 females from TwinsUK, we report that BMI fully mediates the association between the DASH diet and hypertension, explaining 39.1% of the variance in hypertension.We also identify a panel of six common metabolites predicting both the DASH diet and BMI with opposing effects, highlighting common metabolic pathways.Further studies should investigate the underlying molecular mechanisms to increase our understanding of the beneficial ways of treating hypertension. [ABSTRACT FROM AUTHOR]

CVD is the leading cause of death worldwide and, after dementia, is the second biggest cause of death for women. In England, it accounts for one in four of all deaths. Lifestyle modifications represent the primary route both to reduce CVD risk factors and prevent CVD outcomes. Diet constitutes one of the key modifiable risk factors in the aetiology of CVD. We investigated the relationship between nine main dietary indices and a comprehensive range of CVD risk factors in 2590 women from TwinsUK. After adjustment for multiple testing, we found that the Dietary Approaches to Stop Hypertension (DASH) diet was inversely correlated with some of the most common CVD risk factors (BMI, visceral fat (VF), TAG, insulin, homoeostasis model assessment of insulin resistance (HOMA2-IR) and atherosclerotic CVD (ASCVD) risk) with PFDR ranging from 6·28 × 10−7 to 5·63 × 10−4. Similar association patterns were detected across most of the dietary indices analysed. In our post hoc investigation, to determine if any specific food groups were driving associations between the DASH score and markers of cardiometabolic risk, we found that increased BMI, VF, HOMA2-IR, ASCVD risk, insulin and TAG levels were directly correlated with red meat consumption (PFDR ranging from 4·65 × 10−9 to 7·98 × 10−3) and inversely correlated with whole-grain cereal consumption (PFDR ranging from 1·26 × 10−6 to 8·28 × 10−3). Our findings revealed that the DASH diet is associated with a more favourable CVD risk profile, suggesting that this diet may be a candidate dietary pattern to supplement current UK dietary recommendations for CVD prevention. [ABSTRACT FROM AUTHOR]

A healthy diet is associated with the improvement or maintenance of health parameters, and several indices have been proposed to assess diet quality comprehensively. Twin studies have found that some specific foods, nutrients and food patterns have a heritable component; however, the heritability of overall dietary intake has not yet been estimated. Here, we compute heritability estimates of the nine most common dietary indices utilized in nutritional epidemiology. We analyzed 2590 female twins from TwinsUK (653 monozygotic [MZ] and 642 dizygotic [DZ] pairs) who completed a 131-item food frequency questionnaire (FFQ). Heritability estimates were computed using structural equation models (SEM) adjusting for body mass index (BMI), smoking status, Index of Multiple Deprivation (IMD), physical activity, menopausal status, energy and alcohol intake. The AE model was the best-fitting model for most of the analyzed dietary scores (seven out of nine), with heritability estimates ranging from 10.1% (95% CI [.02, .18]) for the Dietary Reference Values (DRV) to 42.7% (95% CI [.36, .49]) for the Alternative Healthy Eating Index (A-HEI). The ACE model was the best-fitting model for the Healthy Diet Indicator (HDI) and Healthy Eating Index 2010 (HEI-2010) with heritability estimates of 5.4% (95% CI [-.17, .28]) and 25.4% (95% CI [.05, .46]), respectively. Here, we find that all analyzed dietary indices have a heritable component, suggesting that there is a genetic predisposition regulating what you eat. Future studies should explore genes underlying dietary indices to further understand the genetic disposition toward diet-related health parameters. [ABSTRACT FROM AUTHOR]

Nutrition plays a key role in blood pressure (BP) regulation. Here, we examine associations between nutrient intakes and BP in a large predominantly female population-based cohort. We assessed the correlation between 45 nutrients (from food frequency questionnaires) and systolic BP/diastolic BP (SBP/DBP) in 3889 individuals from TwinsUK not on hypertensive treatments and replicated in an independent subset of monozygotic twins discordant for nutrient intake (17–242 pairs). Results from both analyses were meta-analysed. For significant nutrients, we calculated heritability using structural equation modelling. We identified and replicated 15 nutrients associated with SBP, 9 also being associated with DBP, adjusting for covariates and multiple testing. 14 of those had a heritable component (h2: 27.1–57.6%). Strong associations with SBP were observed for riboflavin (Beta(SE) = −1.49(0.38), P = 1.00 × 10−4) and tryptophan (−0.31(0.01), P = 5 × 10−4), while with DBP for alcohol (0.05(0.07), P = 1.00 × 10−4) and lactose (−0.05(0.0), P = 1.3 × 10−3). Two multivariable nutrient scores, combining independently SBP/DBP-associated nutrients, explained 22% of the variance in SBP and 13.6% of the variance in DBP. Moreover, bivariate heritability analysis suggested that nutrients and BP share some genetic influences. We confirm current understanding and extend the panel of dietary nutrients implicated in BP regulation underscoring the value of nutrient focused dietary research in preventing and managing hypertension. [ABSTRACT FROM AUTHOR]

Background: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber. Methods: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber intake in UK women (n = 1810) and in a small group of UK men (n = 64). Results: (Poly)phenol intakes correlated with microbiome alpha diversity (Shannon Index) after adjusting for confounders and fiber intake. Moreover, flavonoid intake was significantly correlated with the abundance of Veillonella, (a genus known to improve physical performance), and stilbene intake with that of butyrate-producing bacteria (Lachnospira and Faecalibacterium). Stilbene and flavonoid intake also correlated with lower odds of prevalent obesity (Stilbenes: Odds Ratio (95% Confidence Interval) (OR(95%CI)) = 0.80 (0.73, 0.87), p = 4.90 × 10−7; Flavonoids: OR(95%CI) = 0.77 (0.65, 0.91), p = 0.002). Formal mediation analyses revealed that gut microbiome mediates ~11% of the total effect of flavonoid and stilbene intake on prevalent obesity. Conclusions: Our findings highlight the importance of (poly)phenol consumption for optimal human health. [ABSTRACT FROM AUTHOR]

Objectives: Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection., Design: App-based community survey., Setting: 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373)., Main Exposure: Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020., Main Outcome Measures: SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020., Results: In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts., Conclusion: In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made., Competing Interests: Competing interests: TDS, AMV, ERL and SEB are consultants to Zoe Global Limited ('Zoe'). JW is an employee of Zoe. PCC has research funding from BASF AS and Bayer Consumer Care; is an advisor/consultant to BASF AS, DSM, Danone/Nutricia, Cargill, Smartfish, Nutrileads, Bayer Consumer Care and Pfizer (now GSK) Consumer Healthcare and has received travel reimbursement/speaking fees from Danone, Fresenius Kabi, Pfizer (now GSK) Consumer Healthcare, Smartfish, Biogredia and the California Walnut Commission. ATC has received consulting fees from Bayer Pharma, Pfizer and Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)