Bifidobacteria compensate for genotype in lactose tolerance
The strongest evidence for recent selection on the human genome is the evolution of the lactase-persistence (LP) genotype, which allows lactase production in adults and confers lactose tolerance. Although gut microbes also produce lactose-hydrolyzing enzymes, considerable uncertainty remains about the microbiome's role in lactose tolerance in lactase-non-persistent individuals (LNP). Here we assess microbially-acquired lactose tolerance (MALT) in countries with high (Gabon, Vietnam) and low (Germany) LNP prevalence, and identify MALT-associated gut microbes. Genotyping and lactose-tolerance testing with H2/CH4 and blood glucose measurements in 480 individuals revealed 371 LNPs, 13% of which exhibited lactose tolerance by clinical criteria in each location. LNP subjects with MALT, whose microbiomes exhibited lactose fermentation in vitro, had significantly higher levels of Bifidobacterium compared to those without MALT. Our results indicate that Bifidobacteria confer MALT across populations with different histories of dairying. Detailed comparison of the carbohydrate utilization profiles of Bifidobacterium genomes, derived from isolates and metagenomes and belonging to 14 species, showed remarkable diversity that differed by species but not by location. Our results suggest that Bifidobacteria access an array of dietary carbohydrates similarly across populations. Bifidobacteria share a long evolutionary history with humans that precedes the evolution of LP. Our results indicate that by conferring MALT, Bifidobacteria facilitated dairying, set the stage for canalization by the human genome of adult lactose utilization, and imposed balancing selection for LP/LNP genotypes in dairying societies.