• Interplay Between Host Genetics and Microbiome in Health and Disease
  • Seyed Mohammad Kasra Esfahani,1 Zahra Aghelan,2,* Kimia Sadat Esfahani,3
    1. Department of Medical Laboratory Sciences, TeMS.C., Islamic Azad University, Tehran, Iran
    2. Department of Clinical Biochemistry, TeMS.C., Islamic Azad University, Tehran, Iran
    3. Department of Genetics, Faculty of Advanced Sciences and Technology, TeMS.C., Islamic Azad University, Tehran, Iran


  • Introduction: The human microbiome represents a dynamic and intricate ecosystem of microorganisms that reside throughout the body and significantly influence overall health. Its composition is shaped by a complex interplay of host-related and environmental factors, including human genetic background. Microbial communities are highly diverse at the strain level, exhibiting notable genetic variation not only between individuals but also within the same host over time. Advances in metagenomic analyses have revealed that microbial populations in the human gut can undergo rapid evolutionary changes, driven by factors such as microbial competition and the introduction of novel strains. These adaptive shifts are often influenced by personalized and contextual elements, including dietary habits, geographic location, and antibiotic exposure. Notably, diet and regional environment play dominant roles in shaping microbial strain diversity and driving evolutionary processes. Emerging evidence highlights the significance of microbial genomic alterations—such as single-nucleotide polymorphisms (SNPs), structural variations (SVs), and copy number variations (CNVs)—in mediating microbiome function and their broader implications for human health. The aim of this study is to investigate the relationship between the microbiome and host genetics in the context of certain diseases.
  • Methods: A total of twenty relevant articles investigating interplay between host genetics and microbiome in health and disease” were identified through searches on PubMed, Web of Science and Scopus databases using predefined keywords. These articles were then selected for review and analysis.
  • Results: Faecalibacterium prausnitzii is a common gut bacterium in healthy adults that displays substantial genetic diversity shaped by age, geography, lifestyle, and diet. A global analysis of metagenomic data identified 12 distinct species-level genome bins (SGBs) within this genus, with regional distribution patterns influenced by dietary habits. For example, starch-degradation genes were enriched in Chinese populations consuming fiber-rich, rice-based diets, while lactose and protein metabolism genes were less prevalent. Strain-level genetic variations in gut microbes have been linked to metabolic diseases such as type 2 diabetes (T2D). Although the abundance of Bacteroides coprocola did not differ between T2D patients and healthy individuals, SNP differences were observed in genes, including glycosyl hydrolases, which are involved in carbohydrate metabolism and T2D drug targeting. Similar strain-specific SNPs were detected in Eubacterium rectale and F. prausnitzii, affecting resistance and regulatory functions. A multi-cohort predictive model combining microbial species, genes, MAGs, and SNPs successfully differentiated gastrointestinal disease (GD) from healthy status, highlighting the diagnostic potential of microbial genomic variation.
  • Conclusion: This study highlights the intricate relationship between host genetics and the gut microbiome, emphasizing how strain-level microbial variations and genomic alterations contribute to human health and disease. Evidence from metagenomic analyses reveals that factors such as diet, geography, and lifestyle shape the genetic diversity of key microbial species. Moreover, specific microbial genetic variants — including SNPs — are associated with diseases such as type 2 diabetes and gastrointestinal disorders. These findings underscore the potential of integrating microbial genomic data into precision medicine approaches, offering promising avenues for disease prediction, prevention, and personalized treatment strategies.
  • Keywords: Gut microbiome, Host genetics, Human microbiome, Microbial diversity