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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.

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Highlights d Human gut microbiome exhibits diurnal rhythmicity across populations and individuals d Obese and T2D individuals show disrupted circadian rhythms in the gut microbiome d Arrhytmic bacterial signatures contribute to risk classification and prediction of T2D d These risk signatures show regional differences in applicability across three cohorts

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.

The human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

This study investigated the volatile compounds produced by bacteria belonging to nine different bacterial groups: Lactobacillus sake, L. farciminis, L. alimentarius, Carnobacterium piscicola, Aeromonas sp., Shewanella putrefaciens, Brochothrix thermosphacta, Photobacterium phosphoreum and Enterobacteriaceae isolated from cold-smoked salmon. Each bacterial group was represented by several strains. In addition, combinations of the groups were examined as well. Sterile blocks of cold-smoked salmon were inoculated, vacuum-packed and stored at 6 degrees C. After 40 days of storage at 6 degrees C, aerobic viable count and pH were recorded, the volatile fraction of the samples was analysed by gas chromatography-mass spectrometry (GC-MS), and spoilage was assessed by sensory evaluation. Among the 81 volatile compounds identified by GC-MS, 30 appeared to be released as a result of bacterial metabolism. Some of the effects of inoculated bacterial strains on the composition of the volatile fraction seemed to be characteristic of certain bacterial species. Sensory analysis showed relationships between bacteria, the composition of the volatile fraction and the organoleptic quality of smoked salmon.