Genetic strategies for sex-biased persistence of gut microbes across human life

Abstract

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.

GH136‐encoding gene (perB) is involved in gut colonization and persistence by Bifidobacterium bifidumPRL2010

“…A previous study had identified per B (for Persistence of Bifidobacteria), predicted to encode a glycosyl hydrolase (GH), i.e., GH136 (Yamada et al., 2017), as a key genetic determinant involved in bifidobacterial gut persistence across human life (Tarracchini et al., 2023). A very similar enzyme, designated LnbX, originally identified in a B. longum subsp.…”

“…However, despite the role of per B/ lnb X in host‐derived glycan utilization, an analysis of all complete and well‐annotated publicly available genome sequences of bifidobacterial species commonly found in the infant gut microbiota, that is, B. bifidum , Bifidobacterium breve , B. longum subsp. longum , and Bifidobacterium pseudocatenulatum , highlighted the non‐ubiquitous nature of per B/ lnb X in bifidobacterial genomes (Tarracchini et al., 2023). While all examined B. bifidum and certain B. longum subsp.…”

“…However, in-depth insights into the amino acid length match coupled with a protein domain check for all genes with a sequence homology with perB revealed that the genomes of only eight bifidobacterial species, i.e., Bifidobacterium aerophilum, B. bifidum, Bifidobacterium colobi, Bifidobacterium imperatoris, Bifidobacterium leontopitheci, Bifidobacterium saguini, and Bifidobacterium samirii, together with a portion (111 out of the 312 tested genomes) of the B. longum subsp. longum strains (Tables S1 and S2) encompassed the GH136 catalytic region corresponding to the FIVAR domain (Tarracchini et al, 2023) and a full-length perB homologue in their genomes. Conversely, all other genomes with a perB homologue did not encode the FIVAR domain or the other domain identified in the perB gene, i.e., a secretion signal peptide, and various beta-helix and Rib domains (Tarracchini et al, 2023), except for the perB homologue of Bifidobacterium jacchi which encodes multiple Rib domains (Figure 2 and Figure S1).…”

“…Indeed, it has been demonstrated that bifidobacterial strains possessing a genetic repertoire for mucin metabolism, including Bifidobacterium bifidum and Bifidobacterium longum subsp. longum , show higher resilience and long‐term colonization in the human gut than strains lacking such genetically predicted ability (Katoh et al., 2023; Tarracchini et al., 2023). Specifically, the more efficient persistence of strains of B. bifidum and B. longum subsp.…”

“…Specifically, the more efficient persistence of strains of B. bifidum and B. longum subsp. longum was attributed to per B, a gene encoding an enzyme belonging to the glycosyl hydrolase family 136 (GH136), which is proposed to facilitate mucin degradation (Tarracchini et al., 2023).…”