Anatomy promotes neutral coexistence of strains in the human skin microbiome

Abstract

What enables strains of the same species to coexist in a microbiome? Here, we investigate if host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin. We reconstruct on-person evolution and migration using 947 C. acnes colony genomes acquired from 16 subjects, including from individual skin pores, and find that pores maintain diversity by limiting competition. Although strains with substantial fitness differences coexist within centimeter-scale regions, each pore is dominated by a single strain. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity. We therefore propose that pore anatomy imposes random single-cell bottlenecks during migration into pores and subsequently blocks new migrants; the resulting population fragmentation reduces competition and promotes coexistence. Our findings imply that therapeutic interventions involving pore-dwelling species should focus on removing resident populations over optimizing probiotic fitness.