A groundbreaking study has illuminated how human blood group genetics intricately influence the oral microbiome, unveiling a complex molecular dialogue between host and bacterial genomes. Researchers have discovered that the common human ABO*A1 genotype exerts a profound effect on the prevalence of a specific bacterial gene cluster within Prevotella species, challenging longstanding assumptions about host-microbe interactions in the oral cavity.
Delving deep into the oral microbiome landscape, this investigation identified that individuals possessing the ABO*A1 allele have an elevated abundance of a glycoside hydrolase gene within Prevotella nanceiensis strains. This enzyme is hypothesized to cleave histo-blood group antigens, specifically those of the A type, thereby facilitating microbial adaptation and presumably providing a nutritional advantage to these bacteria. Strikingly, this association became evident only in persons who are genetic secretors, carrying functional FUT2 alleles, which enable the expression of histo-blood group antigens on mucosal surfaces.
The FUT2 enzyme, encoded by the FUT2 gene, governs the synthesis of type I H antigens on epithelial cells and in secretions. In secretor individuals, these antigens can be further glycosylated into A or B antigens according to the ABO genotype. The study uncovered that secretors with A or AB blood types manifested a 71-77% prevalence of the glycoside hydrolase gene in their oral microbiomes. In contrast, non-secretors or individuals with B or O blood types had significantly lower prevalence rates of 46-48%, underscoring a selective pressure exerted by the host glycosylation pattern on the microbial genetic repertoire.
Through meticulous genomic analysis, the glycoside hydrolase locus, initially annotated as a pseudogene due to presumed truncation, was found to exist as a full-length enzyme homologous to GH95 family α1,2-fucosidases present in Prevotella salivae. This revelation was based on assembly of unmapped reads, which suggested that the bacteria possess the enzymatic machinery to cleave α1,2-fucosyl bonds—components integral to the host’s glycan structures. This ability points toward a mechanism wherein Prevotella leverages host-derived glycans as substrates, thus tightly intertwining bacterial survival strategies with host blood group biology.
Intriguingly, the research indicated a graded influence of different ABO alleles on glycoside hydrolase gene presence, reflective of their varied capacities to produce A antigens. Individuals heterozygous for B alleles demonstrated an antagonistic effect on gene abundance when paired with A1 or A2 alleles, suggesting biochemical competition between A and B glycosyltransferases for modifying histo-blood group antigens. This nuanced genetic interplay highlights the sophistication of host-driven ecological niche construction in microbial communities.
Opposite to the findings in Prevotella, a parallel genomic locus in Rothia mucilaginosa demonstrated an inverse relationship with ABO blood groups, where A, B, and AB blood types correlated with absence rather than presence of specific genetic regions. This association intriguingly occurred irrespective of secretor status, suggesting alternative, FUT2-independent pathways in which ABO influences microbial landscape, possibly involving interactions with blood and endothelial cell-derived antigens synthesized via FUT1 pathways.
Further, the persistence of ABO*A1 genotype effects on microbiome composition in non-secretors implies that ABO blood group modulation of the oral microbial niche transcends FUT2-dependent antigen expression. This raises the prospect that host immune components, such as anti-A and anti-B antibodies produced by plasma cells infiltrating the oral mucosa, contribute to selective pressures shaping bacterial colonization and genetic adaptations. Indeed, bacteria might exploit or mimic host glycans to evade immune surveillance or facilitate colonization, representing a subtle battleground at the molecular interface of host and microbe.
The implications of these findings reverberate beyond academic curiosity; they underscore the intricate co-evolution of human genotypes and microbial communities. Understanding how host blood group antigens dictate bacterial gene content opens new avenues for predicting susceptibility to oral diseases, tailoring personalized dental care, and potentially manipulating microbiomes through glycan-targeting therapies. Prevotella’s enzymatic capacity to utilize A antigens hints at microbiome-mediated nutrient cycling intimately linked to host genotype, a paradigm shift in appreciating the oral ecosystem’s dynamic complexity.
Moreover, this research bridges a critical gap by connecting glycosylation genetics—long studied in immunology and transfusion medicine—to microbial ecology and functional genomics. The notion that host blood type genes can sculpt microbial genetic architectures positions human genetics as an active architect of microbial community function, challenging simplistic views of host-microbe relationships and suggesting a woven evolutionary tapestry shaped by molecular recognition and metabolic interplay.
The study’s use of whole genome sequencing (WGS) metagenomic data, encompassing over 10,000 individuals, marks a significant methodological advance. High-resolution binning of genomic coverage exposed subtle yet pervasive host-genome-microbiome interactions, revealing key microbial genes influenced by human variation. This scalable approach heralds a new era in microbiome research, where integrating human and microbial genomes yields predictive frameworks for health and disease modulation.
Notably, the occurrence of specific glycoside hydrolase genes in bacteria aligns with the proposed enzymatic adaptation to host-derived carbohydrate motifs. The putative cleavage of α1,2-fucosyl linkages by Prevotella’s glycoside hydrolase underscores a tailored microbial strategy to exploit mucosal glycans, analogous to mechanisms reported in the gut microbiome where bacterial enzymes degrade host glycans for nutrition and colonization advantage. This conserved biochemical theme across anatomical sites points to a universal axis of host-microbiome crosstalk mediated through glycobiology.
Equally astonishing is the discovery that ABO effects in Rothia manifest independently of secretor status, a phenomenon demanding further exploration. The genes implicated in Rothia include a 3-isopropylmalate dehydrogenase involved in leucine biosynthesis and a protein with unknown function, suggesting non-canonical metabolic or signaling roles connected to host blood group. Unraveling these pathways could reveal novel microbial mechanisms responding to host factors beyond classic glycosylation landscapes.
Collectively, these revelations articulate a compelling narrative: human genetic variation, particularly in ABO blood group and FUT2 secretor status, orchestrate microbial gene prevalence and thereby shape the oral microbiome at a fine scale. This genetic choreography unravels a sophisticated interface where host glycan diversity not only defines antigenicity and immune recognition but also constructs ecological niches and selective pressures influencing bacterial genetic and functional diversity.
This innovative research sets a foundation for future inquiries into how blood group alleles influence susceptibility to oral diseases, modulate microbiome resilience, and interact with host immunity. By decrypting molecular dialogues at the host-microbiome frontier, science moves closer to harnessing the oral microbiome as a therapeutic target, personalized according to host genetic backgrounds.
In summary, the study vividly demonstrates that oral microbiomes reflect a complex genetic interplay between host blood group polymorphisms and bacterial genomic adaptations. The glycoside hydrolase gene in Prevotella emerges as a keystone functional trait governed by ABO and FUT2 genotypes, revealing how microscopic enzymatic functions resonate with macroscopic human phenotypes. Through such integrative insights, the path forward unfolds toward precision medicine and microbiome-informed health strategies.
Subject of Research: Interactions between human ABO blood group genetics, FUT2 secretor status, and the oral microbiome’s bacterial genomic content, focusing on Prevotella and Rothia species.
Article Title: Human and bacterial genetic variation shape oral microbiomes and health.
Article References:
Kamitaki, N., Handsaker, R.E., Hujoel, M.L.A. et al. Human and bacterial genetic variation shape oral microbiomes and health. Nature (2026). https://doi.org/10.1038/s41586-025-10037-7
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41586-025-10037-7
Keywords: ABO blood group, FUT2 secretor status, oral microbiome, Prevotella, glycoside hydrolase, host genetics, microbial adaptation, histo-blood group antigen, metagenomics, host-microbe interaction, glycosylation, microbial genomics
Tags: ABO*A1 genotype effectscomplex molecular dialogue in microbiomesFUT2 gene influencegenetic secretor statusglycoside hydrolase gene functionhisto-blood group antigenshost-microbe interactionshuman blood group geneticsmicrobial adaptation mechanismsnutritional advantages for bacteriaoral microbiome diversityPrevotella species abundance
