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.

Scale-dependent tipping points of bacterial colonization resistance

“…The structure-induced stability supports the view that community assembly from potential colonizers are shaped by priority effects: whoever invades first enjoys colonization resistance against late invaders. The randomness induced by the order of strain arrival might contribute to the substantial host-to-host variability seen in some host-associated microbial communities 9, 16 .…”

“…In other systems, advection may have to be incorporated to describe chemotaxis (pervious point) or the influence of gravity or fluid flow. Fluid flow is a particularly important aspect in the lumen of the gut 45 but also can also arise in microscopic pores, for instance, in skin pores when sebum is exuded 16 . The setup is effectively one-dimensional . The concentration profile in the narrow crypts of our panflute device is approximately uniform along the directions perpendicular to the symmetry axis of the crypts.…”

“…In other systems, advection may have to be incorporated to describe chemotaxis (pervious point) or the influence of gravity or fluid flow. Fluid flow is a particularly important aspect in the lumen of the gut 45 but also can also arise in microscopic pores, for instance, in skin pores when sebum is exuded 16 .…”

“…The ubiquity of micro-habitat associated stability and colonization resistance raises the question of whether these features generically emerge in confined spaces, for example soil pores 13–15 , skin follicles 4, 16 , or crypts and folds in gut-like environments 5,17,18 . Previous studies have identified biological features, such as suppressed biofilm growth or the expression of specific adhesion molecules, that promote stability in specific systemsb 1, 7, 19–21 .…”

Detecting bacterial adaptation within individual microbiomes

“…It may seem surprising that, despite this potential, the first studies of within-person bacterial evolution in the microbiome at a genomic scale have only emerged within the past five years [8,[35][36][37][38]. Within-person adaptation is probably underappreciated because of both theoretical misconceptions and technical limitations of the most popular approaches in the microbiome field.…”