The Dutch Microbiome Project defines factors that shape the healthy gut microbiome

Abstract

The gut microbiome is associated with diverse diseases, but the universal signature of an (un)healthy microbiome remains elusive and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. To fill this gap, we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We then correlated this to 241 host and environmental factors, including physical and mental health, medication use, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is primarily shaped by environment and cohousing. Only ∼13% of taxa are heritable, which are enriched with highly prevalent and health-associated bacteria. By identifying 2,856 associations between microbiome and health, we find that seemingly unrelated diseases share a common signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, of which numerous early-life and current factors are particularly linked to the microbiome. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

“…Another study found an increase in family Desulfovibrionaceae in individuals with high alcohol consumption 48 , and family Desulfovibrionaceae, genus Desulfovibrio and other related taxa were also associated with increased consumption of alcohol in our DMP cohort 16 , supporting a pleiotropic effect of this locus on both microbiome and alcohol intake. These studies, together with our findings, suggest that gut microbiota could indirectly influence an individual's food preferences by mediating the downstream effect of consumption of different products.…”

“…We further investigated the effect of diet at the LCT and ABO loci, taking into account the dominant inheritance model at LCT and the dependence on secretor status at ABO. From 21 dietary factors derived from a food questionnaire, we considered those previously found to be associated (FDR < 0.05) with the microbial taxa and pathway abundances showing genome-wide association signals in these two loci (see Methods) 16 . For the genus Collinsella and pathway LACTOSECAT-PWY, no dietary factors were found at this FDR threshold, we therefore considered the same diet factors associated to B. bifidum in the analyses, given that they showed similar patterns of genetic association.…”

“…We evaluated the robustness of genome-wide associated signals by incorporating the following potential confounders into our statistical model: medication usage, anthropometric data and stool frequency and consistency data (collection and processing was described in Gacesa et al 16 ). We Table 1) using the same software used for GWAS (SAIGE, Zhou et al 19 ).…”

“…In addition, the microbial variation explained by all the factors incorporated in models were also provided as adjusted r 2 . The diet factors used (Methods; Gacesa et al16 ) are: average daily Glycemic load (EXP.DIET.Amoungs.GlycLoadTotal), average daily total food intake kcal (EXP.DIET.Amounts.KcalTotal), average daily alcohol intake, energy corrected (g of alcohol per day * [kcal of alcohol / g of alcohol] / total food intake kcal) (EXP.DIET.ECorrected.AlchAll), DIET.ECorrected.CarbsAll), average daily intake of maltose, energy corrected (EXP.DIET.ECorrected.CarbsMaltose), average daily intake of polysaccharides, energy corrected (EXP.DIET.ECorrected.CarbsPoly), average daily intake of lactose, energy corrected (EXP.DIET.ECorrected.CarbsLactose), average daily intake of sucrose, energy corrected (EXP.DIET.ECorrected.CarbsSuchrose), average daily intake of protein (of any type), energy corrected (EXP.DIET.ECorrected.ProtAll), average daily intake of animal protein, energy corrected (EXP.DIET.ECorrected.ProtAnimal), carb to fat ratio = average daily intake of all carbs / average daily intake of all fats (EXP.DIET.Ratios.CarbToFat), carb to protein ratio = average daily intake of all carbs / average daily intake of protein (EXP.DIET.Ratios.CarbToProtein), low carb diet score (EXP.DIET.Scores.LowCarb) with data sorted into 10 deciles based on total carb…”

Gut Microbiome Dysbiosis is Associated with Increased Mortality following Solid Organ Transplantation

“…We also included 1,183 pro led metagenomes from identically processed samples from age-, sex-and BMImatched healthy DMP controls ( Fig. 1) 21 . To analyze the gut microbiome in end-stage disease, 87 ESLD and 78 ESRD patient samples were collected prior to transplantation.…”