Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort. Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration. Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences. VIDEO ABSTRACT.

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Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough-leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention. We demonstrate statistically significant interpersonal variability in the glycemic response to different bread types, suggesting that the lack of phenotypic difference between the bread types stems from a person-specific effect. We further show that the type of bread that induces the lower glycemic response in each person can be predicted based solely on microbiome data prior to the intervention. Together, we present marked personalization in both bread metabolism and the gut microbiome, suggesting that understanding dietary effects requires integration of person-specific factors.

The bimane fluorescent labels, monobromobimane, dibromobimane, and monobromotrimethylammoniobimane, are derivatives of syn-9,10-dioxabimane:1,5-diazabicyclo[3.3.0]octa-3,6-diene-2,8-dione. They efficiently label hemoglobin (reactive thiol groups), membrane proteins, and glutathione of normal human red cells under physiological conditions. Monobromobimane and dibromobimane are effective on intact cells while red cell membranes may be impermeable to the positively charged monobromotrimethylammoniobimane, the latter being effective only on lysed cells. These bimane labels provide a class of labeling agents that may have wide applicability in biological materials. syn-9,10-Dioxabimanes, a new class of compounds, are highly fluorescent (1). Exceptions to this generalization are the essentially nonfluorescent bromoderivatives, illustrated by a monobromobimane (mBBr) (I), a dibromobimane (bBBr) (II), and a monobromotrimethylammoniobimane (qBBr) (III). We have now found that these three bromobimanes are highly efficient labeling agents for cells, proteins, and small molecules like glutathione, giving rise to highly fluorescent derivatives. The fluorescent derivatives are very stable in air and under irradiation. The labeling procedures are simple and can be carried out rapidly under physiological conditions. We shall describe in the present article the use of these reagents on normal human red cells. MATERIALS AND METHODSBromobimanes. The synthesis of the bromobimanes is described elsewhere (1). mBBr and bBBr were dissolved in acetonitrile and the 50 mM stock solutions were stored in the dark; the solutions are stable for at least 2 months. The salt, qBBr, was dissolved in aqueous buffer (pH 7.4) shortly before use; the 1-4 mM solutions have a half-life at 220C of approximately 4 hr.Red Cells. Human blood, anticoagulated with heparin, was obtained from normal individuals. The buffy coat was removed after centrifugation; the red cells were washed twice with 135 mM NaCI/10 mM phosphate buffer, pH 7.4, and resuspended in the same buffer to a packed cell volume of 5-10%. Ghosts were obtained from the cells by the procedure of Steck and Kant (2). Hemoglobin solutions were prepared by the centrifugation of lysed red cells at 22,000 X g for 30 min, followed by dialysis of the membrane-free supernatants against 10 mM phosphate buffer, pH 7.4.Reactions of Bromobimanes with Intact Cells, Lysates, and Hemoglobin Solutions. The reagents were added in a ratio of 5-20 ,umol of reagent per ml of packed red cells (1-4 moles of reagent per mole of hemoglobin). Usually 10-20 Aul of the stock solution was used per ml of cell suspension of 5-10% packed cell volume. The reagent solution was placed in a dry test tube and the-sample (cell suspension, hemoglobin solution) was added with rapid mixing. A stock solution (50 mM) of the mBBr reagent could be diluted with buffer to 1-2 mM before it was mixed with a sample. The bBBr compound, which is less soluble in water, was not diluted. qBBr was dissolved in buffer immediately before use...