The collection of fecal material and developments in sequencing technologies have enabled cost-efficient, standardized, and non-invasive gut microbiome profiling. As a result, microbiome composition data from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterized due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a large, well-phenotyped, and representative population cohort (n = 7211, FINRISK 2002; Finland). We report specific taxonomic and functional signatures related to the Enterobacteriaceae family in the human gut microbiome that predict mortality during a 15-year follow-up. These associations can be observed both in the Eastern and Western Finns who have differing genetic backgrounds, lifestyles, and mortality rates. Our results supplement previously reported cross-sectional associations, and help to establish a methodological and conceptual basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status. These findings could serve as a solid framework for microbiome profiling in clinical risk prediction, paving the way towards clinical applications of human microbiome sequencing aimed at prediction, prevention, and treatment of disease.

Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their diversification. Direct evidence for N-provisioning by internally housed symbionts is rare in animals; among the ants, it has been documented for just one lineage. In this study we dissect functional contributions by bacteria from a conserved, multi-partite gut symbiosis in herbivorous Cephalotes ants through in vivo experiments, (meta)genomics, and in vitro assays. Gut bacteria recycle urea, and likely uric acid, using recycled N to synthesize essential amino acids that are acquired by hosts in substantial quantities. Specialized core symbionts of 17 studied Cephalotes species encode the pathways directing these activities, and several recycle N in vitro. These findings point to a highly efficient N-economy, and a nutritional mutualism preserved for millions of years through the derived behaviors and gut anatomy of Cephalotes ants.CategoryBiological Sciences-Evolution

Microbes produce an array of secondary metabolites that perform diverse functions from communication to defense. These metabolites have been used to benefit human health and sustainability. In their analysis of the Genomes from Earth's Microbiomes (GEM) catalog, Nayfach and co-authors observed that, whereas genes coding for certain classes of secondary metabolites are limited or enriched in certain microbial taxa, "specific chemistry is not limited or amplified by the environment, and that most classes of secondary metabolites can be found nearly anywhere". Although metagenome mining is a powerful way to annotate biosynthetic gene clusters (BCGs), chemical evidence is required to confirm the presence of metabolites and comprehensively address this fundamental hypothesis, as metagenomic data only identify metabolic potential. To describe the Earth's metabolome, we use an integrated omics approach: the direct survey of metabolites associated with microbial communities spanning diverse environments using untargeted metabolomics coupled with metagenome analysis. We show, in contrast to Nayfach and co-authors, that the presence of certain classes of secondary metabolites can be limited or amplified by the environment. Importantly, our data indicate that considering the relative abundances of secondary metabolites (i.e., rather than only presence/absence) strengthens differences in metabolite profiles across environments, and that their richness and composition in any given sample do not directly reflect those of co-occurring microbial communities, but rather vary with the environment.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that include many antibiotics and a variety of other bioactive compounds. While recent breakthroughs in RiPP discovery raised the challenge of developing new algorithms for their analysis, peptidogenomic-based identification of RiPPs by combining genome/metagenome mining with analysis of tandem mass spectra remains an open problem. We present here MetaRiPPquest, a software tool for addressing this challenge that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just six genomic and metagenomic datasets, MetaRiPPquest identified 27 known and discovered 5 novel RiPP natural products. 1 spectra of natural products. However, to transform natural product discovery into a high-throughput technology and to fully realize the promise of the GNPS project, new algorithms are needed for natural products discovery 6-10 . Indeed, while spectra in the GNPS molecular network represent a gold mine for future chemical discoveries, their interpretation remains a bottleneck due to the large volume of data produced by modern mass spectrometers and unavailability of computational platforms for data processing.The efforts present herein focus on Ribosomally synthesized and Post-translationally modified Peptides (RiPPs), a rapidly expanding group of natural products with applications in pharmaceutical and food industries 11 . RiPPs are produced by RiPP Synthetases (RiPPS) through the Post Ribosomal Peptide Synthesis (PRPS) pathway 11 . RiPPs are initially synthesized as precursor peptides, encoded by RiPP structural genes. The RiPP structural genes are often quite short, making their annotation difficult 12 . A precursor peptide consists of a prefix leader peptide appended to a suffix core peptide. A leader peptide is important for recognition by the RiPP post-translational modification enzymes and for exporting the RiPP out of the cell. The core peptide is post-translationally modified by the RiPP biosynthetic machinery, proteolytically cleaved from the leader peptide to yield the mature RiPP, and exported out of the cell by transporters. The precursor peptide and the enzymes responsible for post-translational modifications (PTMs), proteolytic cleavage, and transportation usually appear in a contiguous biosynthetic gene cluster (BGC) of a RiPP within a microbial genome. The length of the microbial RiPP-encoding BGCs typically varies from 1,000 to 40,000 bp (average length 10,000 bp), larger than the current length of short reads generated by next generation sequencing (350bp), and making DNA assembly a critical part of any short read based RiPP discovery method.Genome mining refers to the informatics-based structural interpretation of a natural product BGC to infer information about the natural product itself. The discoveries of coelichelin in Streptomyces coelicolo...

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