Two modes of evolution shape bacterial strain diversity in the mammalian gut for thousands of generations

Abstract

How and at what pace bacteria evolve when colonizing healthy hosts remains unclear. Here, by monitoring evolution for more than six thousand generations in the mouse gut, we show that the successful colonization of an invader Escherichia coli depends on the diversity of the existing microbiota and the presence of a closely related strain. Following colonization, two modes of evolution were observed: one in which diversifying selection leads to long-term coexistence of ecotypes and a second in which directional selection propels selective sweeps. These modes can be quantitatively distinguished by the statistics of mutation trajectories. In our experiments, diversifying selection was marked by the emergence of metabolic mutations, and directional selection by acquisition of prophages, which bring their own benefits and costs. In both modes, we observed parallel evolution, with mutation accumulation rates comparable to those typically observed in vitro on similar time scales. Our results show how rapid ecotype formation and phage domestication can be in the mammalian gut.

Shared evolutionary path in social microbiomes

“…Parallel mutations, a sign of adaptive evolution, were noticed as previously (Barroso-Batista et al 2014; Frazão et al 2019; Barroso-Batista, Pedro, Sales-Dias, Catarina J.G. Pinto, et al 2020; Frazão et al 2022), being present in both the E. coli populations isolated from animals in social and asocial settings ( Table 5 ). Adaptive mutations, such as psuK/fruA and frlR , could be traced back by sequencing populations from previous sampling points.…”

“…Bacterial evolution in the mammalian intestine has been studied mainly under asocial conditions, where bacterial transmission among mammalian healthy hosts does not take place (Barroso-Batista et al 2014; Barroso-Batista et al 2015; Lourenço et al 2016; Lescat et al 2017; Sousa et al 2017; Frazão et al 2019; Ghalayini et al 2019; Ramiro et al 2020; Frazão et al 2022). To our knowledge, the evolution of E. coli in the presence versus absence of bacterial transmission in mice bearing a microbiota is compared here for the first time.…”

“…Emerging data in both mice and humans shows that significant evolutionary change can occur within strains of each microbiota species (Garud and Pollard 2020). In germ-free mice colonized with either a single or multiple strains of commensal bacteria (Li et al 2015; Barroso-Batista, Pedro, Sales-Dias, Catarina J. G. Pinto, et al 2020; Yilmaz et al 2021) or in mice with a native microbiota (Barroso-Batista et al 2014; Lescat et al 2017; Frazão et al 2019; Frazão et al 2022), evolutionary change has been observed within days, weeks or months. Time series data of human metagenomes also show that several adaptive evolutionary events can occur within months (Garud et al 2019; Zhao et al 2019).…”

Challenges and opportunities of strain diversity in gut microbiome research

“…Additionally, as strains are separated by time and space, some amount of genetic drift can occur further differentiating strains (Bolotin and Hershberg, 2016). Recent experimental models investigated E. coli evolution in the context of host colonization following antibiotic-mediated engraftment (Frazão et al, 2022). Even in time scales of weeks with an estimated >6,000 bacterial generations, the authors uncovered both diversifying selection supporting coexistence of strains and directional selective sweeps which were determined to predominantly arise from new mutations and prophage acquisition, respectively.…”

Native microbiome dominates over host factors in shaping the probiotic genetic evolution in the gut

“…Overall, strain-level diversity of both probiotic strains increased far more rapidly and more drastically within a short timeframe than many other tested bacterial strains, such as host-associated pathogens 9 . For example, Frazão et al took > 100 days (> 6,000 generations) to obtain two divergent lineages of E. coli by monitoring its evolution in mice 10 .…”