๐ก While the impact of host genetics on gut microbial diversity and specific taxa abundance is well-established, understanding how host genetics regulates the genetic diversity of gut microorganisms remains largely unexplored. This study conducted a meta-analysis investigating associations between human genetic variation and gut microbial structural variation in a large cohort, revealing novel insights into the reciprocal hostโmicrobiome relationship.
๐ Methods and Cohorts:
๐ Study Design: Meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Replication of findings in a Tanzanian cohort to account for different genetic backgrounds and lifestyles.
๐ SV Detection and Analysis: Utilized SGV-Finder to identify structural variations (SVs) in 108 gut microbial species, including deletions (dSVs) and variable SVs (vSVs). Selection of 3,552 SVs from 49 bacterial taxa for association analyses after applying stringent criteria.
๐ Heritability Estimates: Estimated heritability of SVs using family-based analyses, revealing a heritable dSV in ๐. ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช with an estimated h2 of 0.38. Detected nominally significant heritability for additional dSVs and vSVs, indicating a genetic component in microbial SV variation.
๐ Key Findings:
๐ ABO Blood Group Association: Identified a strong association between the human ABO-encoded A blood group and a genomic fragment in ๐. ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช harboring a GalNAc metabolism gene cluster.
Replicated this association in a Tanzanian cohort, emphasizing the robustness of the findings across diverse populations.
๐ GalNAc Utilization Pathway: Conducted in vitro experiments demonstrating that GalNAc can serve as the sole carbohydrate source for ๐. ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช strains carrying the GalNAc-metabolizing pathway. Revealed that genomic inversion in ATCCโ27768 affected the expression of GalNAc uptake genes, influencing pathway functionality.
๐ Cardiometabolic Health Associations: Associated GalNAc utilization genes with the hostโs cardiometabolic health, particularly in individuals with mucosal A-antigen. Suggested potential implications for microbial diversity, richness, and associations with blood glucose, Bristol stool type, and general health.
๐ Implications for Human Health: Highlighted the relevance of the ABO locus in human health through its impact on the gut microbiome, expanding the known mechanisms associated with ABO blood groups. Proposed potential benefits of increasing GalNAc-utilizing strains like ๐. ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช ๐ข๐ฏ๐ฅ ๐. ๐ข๐ฆ๐ณ๐ฐ๐ง๐ข๐ค๐ช๐ฆ๐ฏ๐ด to enhance microbial diversity and promote overall health, especially in individuals with mucosal A-antigen.
๐ This study provides a comprehensive analysis of host genetic associations with gut microbial structural variations, uncovering the impact of the ABO blood group on ๐. ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช and its GalNAc utilization pathway. The findings expand our understanding of the intricate interplay between host genetics and the gut microbiome, offering potential avenues for targeted interventions to promote microbial diversity and improve human health.
Link to the Article : http://tinyurl.com/5fx8p79e
