Reichlin, M. | bioRxiv Science

bioRxiv2024

Multi-layered ecological interactions determine growth of clinical antibiotic-resistant strains within human microbiomes

Understanding the spread of antibiotic-resistant bacteria in human-associated microbial communities, particularly in the gut microbiome, is critical for combating the global resistance crisis. However, the role of various ecological factors, such as intraspecies or interspecies interactions, in modulating this process is poorly understood. We hypothesized that different strains within the same species would exhibit distinct interactions with the resident microbiota, leading to variable invasion outcomes. To test this, we examined the population growth of multiple clinically relevant antibiotic-resistant E. coli strains carrying ESBL and carbapenemase resistance plasmids. We introduced these strains into human gut microbiome samples from healthy individuals, using replicated anaerobic microcosms treated or untreated with antibiotics. We found that while antibiotic exposure significantly influenced the growth of these incoming strains, some were successful even in the absence of antibiotics. The variation in ecological success across strain-microbiome sample combinations was positively associated with the intrinsic growth capacities of the strains in local abiotic conditions and their competitive interactions with resident E. coli. Furthermore, the incoming resistant strains had strain- specific effects on the taxonomic composition of the resident microbiota; different strains not only varied in their growth performance in human microbiomes, in some cases they pushed taxonomic composition of the resident community in different directions. In contrast with phenotypes measured in gut microcosms, metabolic profiles measured across various single-carbon-source environments were not reliable predictors of population growth in human microbiomes. Overall, this controlled design reveals the multi-layered ecological dynamics and strain-specific mechanisms that govern the spread of antibiotic-resistant bacteria in individual human-associated microbiomes.

microbiology↗

bioRxiv2023

Mapping gut bacteria into functional niches reveals the ecological structure of human gut microbiomes

Microbiomes are an essential contributor to the metabolic activity in the human gastrointestinal tract. The fermentation of otherwise indigestible nutritional components like dietary fibers relies on a complex interplay of metabolic pathways that are distributed across the individual bacteria. Yet, which of the bacteria are responsible for which parts of the distributed metabolism and how they should be grouped together is insufficiently understood. Here, we present the NicheMap, an approach to map the different bacterial taxa that make up the gut microbiome onto the different functional niches of microbial carbohydrate fermentation. Our approach uses in vitro measurements of bacterial growth and metabolic activity to identify which bacterial taxa are responsible for which metabolic function in the relevant complex context of whole human fecal microbiomes. We identified characteristic taxa selected for by a panel growth substrates representative of dietary components that are resistant to digestion by host enzymes. These characteristic taxa offer predictions of which bacteria are stimulated by the various components of human diet. We validated these predictions using microbiome data from a human nutritional supplementation study. We suggest a template of how bacterial taxonomic diversity is organized along the trophic cascade of intestinal carbohydrate fermentation. We anticipate that our results and our approach will provide a key contribution towards building a structure-function map for gut microbiomes. Having such a map on hand is an important step in moving the microbiome from a descriptive science to an interventional one.

microbiology↗