By tracking the spread of adaptive genes in gut bacteria across continents, researchers have identified a significant evolutionary response to modern diets and lifestyles. A recent study published in Nature introduces an integrated linkage disequilibrium score (iLDS), a new tool for detecting adaptive alleles moving through human gut microbiomes via recombination and horizontal gene transfer.
Gut bacteria are known to evolve quickly, with new mutations becoming common in healthy adults within short periods. These changes can spread between individuals, especially through horizontal gene transfer—a process by which genes move between different bacterial strains or species. This mechanism is particularly important for the spread of antibiotic resistance genes.
The research team used simulations to determine whether positive selection increases genetic linkage between non-synonymous variants compared to synonymous ones. Their findings showed that such patterns only emerge under positive selection and not by chance, even when accounting for various evolutionary scenarios.
To see if these genetic signatures occur naturally, the researchers analyzed metagenomic data from 693 people across three continents. They examined 3,316 haplotypes from 32 species of gut bacteria and found that most species showed higher linkage among common non-synonymous variants—evidence of positive selection—while rare variants reflected purifying selection.
The iLDS statistic was designed to detect regions of recent positive selection by measuring overall and non-synonymous linkage disequilibrium. When tested on both simulated data and real-world samples of Clostridioides difficile, iLDS accurately pinpointed regions known for selective sweeps, such as tcdB and S-layer cassette loci.
In total, iLDS identified 155 selective sweeps affecting 447 genes across 32 gut microbiome species. Genes involved in carbohydrate metabolism and transport—including starch utilization genes susC/susD and glycoside hydrolases—were frequently targeted by selection. Notably, mdxE and mdxF genes related to maltodextrin transport were under strong selection in starch-metabolizing bacteria and showed evidence of recent recombination events.
Industrialization has been linked with reduced microbiome diversity but increased rates of gene transfer. The study’s scans revealed that while most selective sweeps were unique to specific populations—indicating local adaptation—some were globally widespread. Industrialized populations shared more sweeps among themselves than with non-industrialized groups, suggesting similar dietary pressures drive these changes.
Only three sweeps were shared between industrialized and non-industrialized groups; thirty-two were unique to one group or the other. For example, the Ruminococcus bromii mdxEF locus was under selection in all industrialized populations but not in non-industrialized ones—a possible sign of adaptation to modern diets.
Although hundreds of selective sweeps were detected using iLDS, researchers believe this may underestimate the true extent of positive selection due to conservative calibration methods. Further investigation into these loci could improve understanding of how microbiome genetics affect human health and guide development of disease diagnostics or targeted probiotics.
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