The gut microbiome is shaped by diet and influences host metabolism, but these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of >1,100 gut microbiomes from individuals with detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements. We found strong associations between microbes and specific nutrients, foods, food groups, and general dietary indices, driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across cohorts, and blood markers of cardiovascular disease and impaired glucose tolerance were more strongly associated with microbiome structure. While some microbes such as Prevotella copri and Blastocystis spp., were indicators of reduced postprandial glucose metabolism, several species were more directly predictive for postprandial triglycerides and C-peptide. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favourable cardiometabolic and postprandial markers, indicating our large-scale resource can potentially stratify the gut microbiome into generalizable health levels among individuals without clinically manifest disease. Fig. 1: The PREDICT 1 study associates gut microbiome structure with habitual diet and blood cardiometabolic markers. (A)The PREDICT 1 study assessed the gut microbiome of 1,098 volunteers from the UK and US via metagenomic sequencing of stool samples. Phenotypic data obtained through in-person assessment, blood/biospecimen collection, and the return of validated study questionnaires queried a range of relevant host/environmental factors including (1) personal characteristics, such as age, BMI, and estimated visceral fat; (2) habitual dietary intake using semi-quantitative food frequency questionnaires (FFQs);(3) fasting; and (4) postprandial cardiometabolic blood and inflammatory markers, total lipid and lipoprotein concentrations, lipoprotein particle sizes, apolipoproteins, derived metabolic risk scores, glycaemic-mediated metabolites, and metabolites related to fatty acid metabolism. (B) Overall microbiome alpha diversity, estimated as the total number of confidently identified microbial species in a given sample (richness), was correlated with HDL-D (positive) and estimated hepatic steatosis (negative). Up to ten strongest absolute Spearman correlations are reported for each category with q<0.05. Top species based on Shannon diversity are reported in Supplementary Fig. 1A and all correlations are in Supplementary Table 1. Microbial diversity and composition are linked with diet and fasting and postprandial biomarkersWe first leveraged a unique subpopulation of our study comprised of 480 twins to disentangle the confounding effects of shared genetics from other factors on microbiome composition. Our data confirmed that host genetics influences microbiome composition only to a small extent 18 , as intra-twin pair microbiome ...

The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability. While diet can induce a shift in the gut microbiota, these changes appear to be temporary. Whether prolonged dietary changes can induce permanent alterations in the gut microbiota is unknown, mainly due to a lack of long-term human dietary interventions, or long-term follow-ups of short-term dietary interventions. It is possible that habitual diets have a greater influence on the gut microbiota than acute dietary strategies. This review presents the current knowledge around the response of the gut microbiota to short-term and long-term dietary interventions and identifies major factors that contribute to microbiota response to diet. Overall, further research on long-term diets that include health and microbiome measures is required before clinical recommendations can be made for dietary modulation of the gut microbiota for health.

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.

ObjectivePoor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation.DesignWe used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively.ResultsOver 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation.ConclusionsA diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

Background and aimsGut transit time is a key modulator of host–microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the ‘blue dye’ method as an inexpensive and scalable technique to measure transit time.MethodsWe assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study.ResultsWe found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency.ConclusionsGut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.

ObjectivesDietary 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.DesignApp-based community survey.Setting445 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 exposureSelf-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 measuresSARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020.ResultsIn 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.ConclusionIn 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.

Personalised dietary modulation of the gut microbiota may be key to disease management. Current investigations provide a broad understanding of the impact of diet on the composition and activity of the gut microbiota, yet detailed knowledge in applying diet as an actionable tool remains limited. Further to the relative novelty of the field, approaches are yet to be standardised and extremely heterogeneous research outcomes have ensued. This may be related to confounders associated with complexities in capturing an accurate representation of both diet and the gut microbiota. This review discusses the intricacies and current methodologies of diet-microbial relations, the implications and limitations of these investigative approaches, and future considerations that may assist in accelerating applications. New investigations should consider improved collection of dietary data, further characterisation of mechanistic interactions, and an increased focus on -omic technologies such as metabolomics to describe the bacterial and metabolic activity of food degradation, together with its crosstalk with the host. Furthermore, clinical evidence with health outcomes is required before therapeutic dietary strategies for microbial amelioration can be made. The potential to reach detailed understanding of diet-microbiota relations may depend on re-evaluation, progression, and unification of research methodologies, which consider the complexities of these interactions.

ObjectivePoor metabolic health and certain lifestyle factors have been associated with risk and severity of coronavirus disease 2019 (COVID-19), but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its intersection with socioeconomic deprivation.DesignWe used data from 592,571 participants of the smartphone-based COVID Symptom Study. Diet quality was assessed using a healthful plant-based diet score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization with oxygen support, respectively.ResultsOver 3,886,274 person-months of follow-up, 31,815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR, 0.91; 95% CI, 0.88-0.94) and severe COVID-19 (HR, 0.59; 95% CI, 0.47-0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate for lowest vs highest quartile of diet score was 22.5 (95% CI, 18.8-26.3) and 40.8 (95% CI, 31.7-49.8; 10,000 person-months) among persons living in areas with low and high deprivation, respectively.ConclusionsA dietary pattern characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. These association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.