Biology subjects

Yaffe, E.

Publications and source records attributed to Yaffe, E..

5 recordsLinked to original sources

bioRxiv2026

Path-dependent recovery of the gut microbiome after antibiotics emerges from coupled ecological and evolutionary dynamics

Recovery of the gut microbiome after antibiotic exposure is often incomplete and variable, and the processes underlying this variation remain unclear. We performed longitudinal shotgun metagenomic sequencing of 2876 daily fecal samples from replicated humanized and conventional mouse cohorts exposed to controlled antibiotic perturbations. Metagenomic profiling recapitulated ecological trajectories previously observed by 16S sequencing, while revealing extensive strain-level dynamics, including reproducible sweeps of standing variants and de novo mutations in antibiotic target sites and regulatory loci. We also identified genetic changes whose effects depended on community composition, competitive release, and perturbation history. Cross-housing experiments revealed bidirectional strain transfer, with antibiotic-induced niche clearance enabling replacement of resident strains. In parallel, phage dynamics were heterogeneous and clustered by cage. Together, these findings show that post-antibiotic microbiome recovery is a path-dependent process shaped by selection, transmission, and phage activity, producing divergent outcomes even among closely matched communities exposed to the same perturbations.

microbiology↗

bioRxiv2023

A short course of antibiotics selects for persistent resistance in the human gut

Understanding the relationship between antibiotic use and the evolution of antimicrobial resistance is vital for effective antibiotic stewardship, yet animal models and in vitro experiments poorly replicate real-world conditions. To elucidate how resistance evolves in vivo, we exposed 60 human subjects to ciprofloxacin and used longitudinal stool samples and a new computational method to assemble genomes for 5665 populations of commensal bacterial species within subjects. Analysis of 2.27M polymorphic sequence variants revealed 513 populations that underwent selective sweeps. We found convergent evolution focused on DNA gyrase and evidence of dispersed selective pressure at other genomic loci. Nearly 10% of susceptible bacterial populations evolved towards resistance through sweeps that involved mutations in a specific amino acid in gyrase. Evolution towards resistance was predicted by population abundances before and during the exposure. 89% of gyrase sweeps and the majority of all sweeps persisted more than 10 weeks. This work quantifies the direct relationship between antibiotic usage and the evolution of resistance within the gut communities of individual human hosts.

evolutionary biology↗

bioRxiv2022

Profiling of the human intestinal microbiome and bile acids under physiologic conditions using an ingestible sampling device

The spatiotemporal structure of the human microbiome and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, we know little about the distribution of microbes and their products in the gut because of reliance on stool samples and limited access only to some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, we developed and evaluated a safe, ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. The collection of 240 intestinal samples from 15 healthy individuals using the device revealed significant differences between microbes and metabolites present in the intestines versus stool. Certain microbial taxa were differentially enriched, and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Overall, we identified heterogeneous intestinal profiles of bacterial taxa and metabolites indicating that non-invasive multi-regional sampling of the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

microbiology↗

bioRxiv2021

Precise genotyping of circular mobile elements uncovers human associated plasmids with surprisingly recent common ancestors

Mobile genetic elements with circular genomes play a key role in the evolution of microbial communities. These circular genomes correspond to cyclic paths in metagenome graphs, and yet, assemblies derived from natural microbial communities produce graphs riddled with spurious cycles, complicating the accurate reconstruction of circular genomes. We present an algorithm that reconstructs true circular genomes based on the identification of so-called dominant cycles. Our algorithm leverages paired reads to bridge gaps between assembly contigs and scrutinizes cycles through a nucleotide-level analysis, making the approach robust to mis-assembly artifacts. We validated the approach using simulated and reference data. Application of this approach to 32 publicly available DNA shotgun sequence data sets from diverse natural environments led to the reconstruction of hundreds of circular mobile genomes. Clustering revealed 20 clusters of cryptic, prevalent, and abundant plasmids that have clonal population structures with surprisingly recent common ancestors. This work enables the robust study of evolution and spread of mobile elements in natural settings.

genomics↗

bioRxiv2019

Tracking microbial evolution in the human gut using Hi-C

Despite the importance of horizontal gene transfer for rapid bacterial evolution, reliable assignment of mobile genetic elements to their microbial hosts in natural communities such as the human gut microbiota remains elusive. We used Hi-C (High-throughput chromosomal conformation capture), coupled with probabilistic modeling of experimental noise, to resolve 88 strain-level genomes of distal gut bacteria from two subjects, including 12,251 accessory elements. Comparisons of 2 samples collected 10 years apart for each of the subjects revealed extensive in situ exchange of accessory elements, as well as evidence of adaptive evolution in core genomes. Accessory elements were predominantly promiscuous and prevalent in the distal gut metagenomes of 218 adult subjects. This work provides a foundation and approach for studying microbial evolution in natural environments.

microbiology↗