HKBU multidisciplinary research team discovers population-specific patterns in the human gut microbiome

The human gastrointestinal tract hosts a complex ecosystem of microorganisms that plays a pivotal role in maintaining health and modulating disease. Often referred to as the body's "second genome", its composition varies substantially across global populations due to geography, diet, and lifestyle. However, previous research has focused predominantly on relative species abundance, largely ignoring the genomic fine-tuning represented by single nucleotide polymorphisms (SNPs). 

To address this gap, a multidisciplinary team led by Professor Lyu Aiping, Vice-President (Research and Development), and Professor Zhang Lu, Associate Professor from the Department of Computer Science, systematically compared the gut microflora of Han Chinese and non-Chinese populations using a new reference catalogue. 

Geography as the primary driver of microbial variation

In “Exploring differences in the human gut microbiome between Han Chinese and non-Chinese populations”, the researchers compiled the Human Gut Microbiome Reference Genome Catalog (HGMRGC), containing 271,480 non-redundant genomes across 5,785 species-level clusters, to examine population-level distinctions. By evaluating discovery and replication cohorts incorporating thousands of individuals across multiple countries, the study establishes that geographic origin is the primary determinant of gut microbial variation. Geographic location explained more variance in both taxonomic abundance and SNP profiles than age, sex, or body mass index. This dominant influence remains consistent both internationally and across distinct geographical sub-regions within China. 

Dietary adaptations and functional divergence

The underlying genetic differences between populations reflect distinct cultural and dietary habits. For instance, analysis of the genus Collinsella reveals 689 population-specific genome clusters. Han Chinese-specific clusters demonstrates significant enrichment in pathways for beta-glucoside utilisation, facilitating the breakdown of plant-derived fibres. Conversely, non-Chinese clusters are enriched for lactose utilisation pathways, aligning with traditional Western diets rich in dairy products. 

Further genomic adaptations were observed in individual bacterial species. Faecalibacillus intestinalis, a bacterium extremely responsive to dietary interventions, exhibits the strongest geographical divergence, driven by SNP variations in genes linked to carbohydrate metabolism. Similarly, genes involved in lactose processing within Escherichia coli C display reduced genetic variation in non-Chinese cohorts, pointing to stronger evolutionary selection. Meanwhile, Lawsonibacter asaccharolyticus, a species associated with coffee consumption, exhibits far higher genetic diversity among non-Chinese populations. 

Metabolic capabilities, resistance, and health

Beyond carbohydrate processing, 108 species show marked differences in prevalence between the two groups. Han Chinese-prevalent species display greater metabolic capacity for the de novo biosynthesis of B vitamins and vitamin K2, as well as increased glycolysis and glucose utilisation capabilities. However, these species were also enriched in genes conferring resistance to antimicrobial peptides and beta-lactam antibiotics, reflecting historical patterns of antibiotic exposure. Furthermore, Han Chinese-prevalent species carried pathways for trimethylamine production, a metabolite linked to cardiovascular disease risk, suggesting a complex metabolic landscape where protective vitamin synthesis coexists with disease-associated pathways. 

A divergence between abundance and genetic diversity

A crucial insight from the study is the contrasting nature of microbial diversity metrics. Non-Chinese individuals exhibit higher species-level alpha diversity based on microbial abundance. However, when evaluating diversity at the genomic level through SNPs, Han Chinese demonstrate appreciably higher intra-species genetic diversity. Beta diversity analyses further confirm that microbial communities differ far more between populations than within the same population, both in abundance and SNP variations. 

These findings underscore the necessity of incorporating high-resolution genomic data alongside traditional species profiling. By building reference catalogues that represent understudied populations adequately, researchers will better understand how localised evolutionary pressures shape the human microbiome and the broader implications for global health. 

Full paper on Genome Biology: https://pubmed.ncbi.nlm.nih.gov/41545888

Professor Lyu Aiping

School of Chinese Medicine

Professor Zhang Lu

Faculty of Science and Technology