ABSTRACT: Previous studies indicated that populations consuming a Mediterranean diet rich in fiber, vegetables, and fruits have a significantly lower risk of cardiovascular and metabolic diseases than populations of industrialized societies consuming diets enriched in processed carbohydrates, animal proteins, and fats. To explore the potential contributions of gut microbiota to the observed diet-related metabolic effects, we conducted an integrative analysis of distal gut microbiota composition and functions and intestinal metabolites in Egyptian and U.S. teenagers. All Egyptian gut microbial communities belonged to the Prevotella enterotype, whereas all but one of the U.S. samples were of the Bacteroides enterotype. The intestinal environment of Egyptians was characterized by higher levels of short-chain fatty acids, a higher prevalence of microbial polysaccharide degradation-encoding genes, and a higher proportion of several polysaccharide-degrading genera. Egyptian gut microbiota also appeared to be under heavier bacteriophage pressure. In contrast, the gut environment of U.S. children was rich in amino acids and lipid metabolism-associated compounds; contained more microbial genes encoding protein degradation, vitamin biosynthesis, and iron acquisition pathways; and was enriched in several protein- and starch-degrading genera. Levels of 1-methylhistamine, a biomarker of allergic response, were elevated in U.S. guts, as were the abundances of members of Faecalibacterium and Akkermansia, two genera with recognized anti-inflammatory effects. The revealed corroborating differences in fecal microbiota structure and functions and metabolite profiles between Egyptian and U.S. teenagers are consistent with the nutrient variation between Mediterranean and Western diets. IMPORTANCE The human gastrointestinal microbiota functions as an important mediator of diet for host metabolism. To evaluate how consumed diets influence the gut environment, we carried out simultaneous interrogations of distal gut microbiota and metabolites in samples from healthy children in Egypt and the United States. While Egyptian children consumed a Mediterranean diet rich in plant foods, U.S. children consumed a Western diet high in animal protein, fats, and highly processed carbohydrates. Consistent with the consumed diets, Egyptian gut samples were enriched in polysaccharide-degrading microbes and end products of polysaccharide fermentation and U.S. gut samples were enriched in proteolytic microbes and end products of protein and fat metabolism. Thus, the intestinal microbiota might be selected on the basis of the diets that we consume, which can open opportunities to affect gut health through modulation of gut microbiota with dietary supplementations.
