No abstract

A detailed understanding of gut microbial ecology is essential to engineer effective microbial therapeutics and to model microbial community assembly and succession in health and disease. However, establishing generalizable insights into the functional determinants of microbial fitness in the human gut has been a formidable challenge. Here we employ fecal microbiota transplantation (FMT) as an in natura experimental model to identify determinants of microbial colonization and resilience. Our long-term sampling strategy and high-resolution multi-omics analyses of FMT donors and recipients reveal adaptive ecological processes as the main driver of microbial colonization outcomes after FMT. We also show that high-fitness donor microbial populations are significantly enriched in metabolic pathways that are responsible for the biosynthesis of nucleotides, essential amino acids, and micronutrients, independent of taxonomy. To determine whether such metabolic competence can explain the microbial ecology of human disease states, we analyzed genomes reconstructed from healthy humans and humans with inflammatory bowel disease (IBD). Our data reveal that such traits are also significantly enriched in microbial genomes recovered from IBD patients, linking presence of superior metabolic competence in bacteria to their expansion in IBD. Overall, these findings suggest that the transfer of gut microbes from a healthy donor to a disrupted recipient environment initiates an environmental filter that selects for populations that can self-sustain. Such ecological processes that select for self-sustenance under stress offer a model to explain why common yet typically rare members of healthy gut environments can become dominant in inflammatory conditions without any need for them to be causally associated with, or contribute to, such disease states.

Background Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. Results Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. Conclusions These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of “dysbiosis” that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

By offering extremely long contiguous characterization of individual DNA molecules, rapidly emerging long‐read sequencing strategies offer comprehensive insights into the organization of genetic information in genomes and metagenomes. However, successful long‐read sequencing experiments demand high concentrations of highly purified DNA of high molecular weight (HMW), which limits the utility of established DNA extraction kits designed for short‐read sequencing. The challenges associated with input DNA quality intensify further when working with complex environmental samples of low microbial biomass, which requires new protocols that are tailored to study metagenomes with long‐read sequencing. Here, we use human tongue scrapings to benchmark six HMW DNA extraction strategies that are based on commercially available kits, phenol–chloroform (PC) extraction and agarose encasement followed by agarase digestion. A typical end goal of HMW DNA extractions is to obtain the longest possible reads during sequencing, which is often achieved by PC extractions, as demonstrated in sequencing of cultured cells. Yet our analyses that consider overall read‐size distribution, assembly performance and the number of circularized elements found in sequencing results suggest that column‐based kits with enzyme supplementation, rather than PC methods, may be more appropriate for long‐read sequencing of metagenomes.

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