Strain-level analysis of Bifidobacterium spp. from gut microbiomes of adults of differing lactase persistence genotypes

Abstract

One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of Bifidobacterium in adults with lactase gene (LCT) SNPs associated with lactase-non persistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with varying lactase persistence genotypes. We further employed a novel genome-capture based enrichment of Bifidobacterium DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. B. adolescentis and B. longum were the most abundant Bifidobacterium species regardless of host LCT-genotype. LCT- genotypes could not be discriminated based on relative abundances of Bifidobacterium species or Bifidobacterium community structure. Metagenomic analysis of Bifidobacterium-enriched DNA revealed intra-individual temporal stability of B. longum, B. adolescentis, and B. bifidum strains against the background of a changeable microbiome. We also observed greater strain sharing within MZ twin pairs compared to unrelated individuals, and within GG compared to AA/AG individuals, but no effect of host LCTgenotype on Bifidobacterium strain composition. Our results support a "rising tide lift all boats" model for the dominant Bifidobacteria in the adult gut: their higher abundance in lactase-non persistent compared to lactase-persistent individuals results from an expansion at the genus level. Bifidobacterium species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood. IMPORTANCEWhen human populations domesticated animals to drink their milk they adapted genetically with the ability to digest milk into adulthood (lactase persistence). The gut microbiomes of lactase non-persistent people (LNP) differ from those of lactase-persistent people (LP) by containing more bacteria belonging to the Bifidobacteria. These beneficial gut bacteria, which fall into many species, are known to degrade milk in the baby gut. Here, we asked if adult LP and LNP microbiomes differ in the species of Bifidobacteria present. We studied the gut microbiomes of LP and LNP adults, including twins, sampled at several times. In particular, we used a technique to selectively pull out the DNA belonging to the Bifidobacteria: analysis of these DNA segments allowed us to compare Bifidobacteria at the strain level. Our results show that the LNP enhance the abundance of Bifidobacteria regardless of species. We also noted that a persons specific strains are recoverable several years later, and twins tend to share the same ones. Given that Bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long term, multi-generational inheritance.