Dynamics of colonization and transmission in the human gut microbiome

Katherine Xue
David Relman lab and Dmitri Petrov lab, Stanford University
Primer: Tracking strains in the human gut microbiome

The human gut microbiome is a diverse, complex ecosystem that has important impacts on human health. Traditional genomic methods like 16S sequencing and metagenomic profiling provide genus- and species-level resolution of gut microbiome composition, but there is a growing appreciation that strains of the same species can play distinct functional roles in the gut microbiome. However, inferring the strain-level composition of the gut microbiome from metagenomic sequencing data remains a challenging bioinformatic problem. In this talk, we will discuss 1) why strain-level inference is important for understanding the function, ecology, and evolution of the gut microbiome, 2) the challenges associated with inferring strain-level microbiome composition from metagenomic sequencing data, 3) current methods for inferring strain-level microbiome composition, and 4) open problems for the field.

Meeting: Dynamics of colonization and transmission in the human gut microbiome

Humans constantly encounter new microbes, but few become long-term residents of the adult gut microbiome. Classical theories predict that colonization is determined by the availability of open niches, but it remains unclear whether other ecological barriers limit commensal colonization in natural settings. To disentangle these effects, we used a controlled perturbation with the antibiotic ciprofloxacin to investigate the dynamics of gut microbiome transmission in 22 households of healthy, cohabiting adults. Colonization was rare in three-quarters of antibiotic-taking subjects, whose resident strains rapidly recovered in the week after antibiotics ended. In contrast, the remaining subjects exhibited lasting responses to antibiotics, with extensive species losses and transient expansions of potential opportunistic pathogens. These subjects experienced elevated rates of commensal colonization, but only after long delays: many new colonizers underwent sudden, correlated expansions months after the antibiotic perturbation. Furthermore, strains that had previously transmitted between cohabiting partners rarely recolonized after antibiotic disruptions, showing that colonization displays substantial historical contingency. This work demonstrates that there remain substantial ecological barriers to colonization even after major microbiome disruptions, suggesting that dispersal interactions and priority effects limit the pace of community change. 

For more information visit: https://www.broadinstitute.org/mia.