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1. Kairos infers in situ horizontal gene transfer in longitudinally sampled microbiomes through microdiversity-aware sequence analysis

   https://doi.org/10.1101/2023.10.24.563791  

   Brown, Connor L; Cheung, Yat Fei; Song, Haoqiu; Snead, Delaney; Vikesland, Peter; Pruden, Amy; Zhang, Liqing (October 2023, bioRxiv)

   Abstract Horizontal gene transfer (HGT) occurring within microbiomes is linked to complex environmental and ecological dynamics that are challenging to replicate in controlled settings. Consequently, most extant studies of microbiome HGT are either simplistic experimental settings with tenuous relevance to real microbiomes or correlative studies that assume that HGT potential is a function of the relative abundance of mobile genetic elements (MGEs), the vehicles of HGT. Here we introduce Kairos as a bioinformatic tool deployed in nextflow for detecting HGT events “in situ,” i.e., within a microbiome, through analysis of time-series metagenomic sequencing data. Thein-situframework proposed here leverages available metagenomic data from a longitudinally sampled microbiome to assess whether the chronological occurrence of potential donors, recipients, and putatively transferred regions could plausibly have arisen due to HGT over a range of defined time periods. The centerpiece of the Kairos workflow is a novel competitive read alignment method that enables discernment of even very similar genomic sequences, such as those produced by MGE-associated recombination. A key advantage of Kairos is its reliance on assemblies rather than metagenome assembled genomes (MAGs), which avoids systematic exclusion of accessory genes associated with the binning process. In an example test-case of real world data, use of assemblies directly produced a 264-fold increase in the number of antibiotic resistance genes included in the analysis of HGT compared to analysis of MAGs with MetaCHIP. Further,in silicoevaluation of contig taxonomy was performed to assess the accuracy of classification for both chromosomally- and MGE-derived sequences, indicating a high degree of accuracy even for conjugative plasmids up to the level of class or order. Thus, Kairos enables the analysis of very recent HGT events, making it suitable for studying rapid prokaryotic adaptation in environmental systems without disturbing the ornate ecological dynamics associated with microbiomes. Current versions of the Kairos workflow are available here:https://github.com/clb21565/kairos. 

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2. Modeling the ecology of parasitic plasmids

   https://doi.org/10.1038/s41396-021-00954-6  

   Lopez, Jaime G.; Donia, Mohamed S.; Wingreen, Ned S. (April 2021, The ISME Journal)

   Abstract Plasmids are autonomous genetic elements that can be exchanged between microorganisms via horizontal gene transfer (HGT). Despite the central role they play in antibiotic resistance and modern biotechnology, our understanding of plasmids’ natural ecology is limited. Recent experiments have shown that plasmids can spread even when they are a burden to the cell, suggesting that natural plasmids may exist as parasites. Here, we use mathematical modeling to explore the ecology of such parasitic plasmids. We first develop models of single plasmids and find that a plasmid’s population dynamics and optimal infection strategy are strongly determined by the plasmid’s HGT mechanism. We then analyze models of co-infecting plasmids and show that parasitic plasmids are prone to a “tragedy of the commons” in which runaway plasmid invasion severely reduces host fitness. We propose that this tragedy of the commons is averted by selection between competing populations and demonstrate this effect in a metapopulation model. We derive predicted distributions of unique plasmid types in genomes—comparison to the distribution of plasmids in a collection of 17,725 genomes supports a model of parasitic plasmids with positive plasmid–plasmid interactions that ameliorate plasmid fitness costs or promote the invasion of new plasmids. 

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3. A ridge-to-reef ecosystem microbial census reveals environmental reservoirs for animal and plant microbiomes

   https://doi.org/10.1073/pnas.2204146119  

   Amend, Anthony S.; Swift, Sean O.; Darcy, John L.; Belcaid, Mahdi; Nelson, Craig E.; Buchanan, Joshua; Cetraro, Nicolas; Fraiola, Kauaoa M.; Frank, Kiana; Kajihara, Kacie; et al (August 2022, Proceedings of the National Academy of Sciences)

   Microbes are found in nearly every habitat and organism on the planet, where they are critical to host health, fitness, and metabolism. In most organisms, few microbes are inherited at birth; instead, acquiring microbiomes generally involves complicated interactions between the environment, hosts, and symbionts. Despite the criticality of microbiome acquisition, we know little about where hosts’ microbes reside when not in or on hosts of interest. Because microbes span a continuum ranging from generalists associating with multiple hosts and habitats to specialists with narrower host ranges, identifying potential sources of microbial diversity that can contribute to the microbiomes of unrelated hosts is a gap in our understanding of microbiome assembly. Microbial dispersal attenuates with distance, so identifying sources and sinks requires data from microbiomes that are contemporary and near enough for potential microbial transmission. Here, we characterize microbiomes across adjacent terrestrial and aquatic hosts and habitats throughout an entire watershed, showing that the most species-poor microbiomes are partial subsets of the most species-rich and that microbiomes of plants and animals are nested within those of their environments. Furthermore, we show that the host and habitat range of a microbe within a single ecosystem predicts its global distribution, a relationship with implications for global microbial assembly processes. Thus, the tendency for microbes to occupy multiple habitats and unrelated hosts enables persistent microbiomes, even when host populations are disjunct. Our whole-watershed census demonstrates how a nested distribution of microbes, following the trophic hierarchies of hosts, can shape microbial acquisition. 

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4. Microbiome metabolic capacity is buffered against phylotype losses by functional redundancy

   https://doi.org/10.1128/aem.02368-24  

   Cross, Kayla; Beckman, Noelle; Jahnes, Benjamin; Sabree, Zakee L (February 2025, Applied and Environmental Microbiology)

   Rudi, Knut (Ed.)

   ABSTRACT Many animals contain a species-rich and diverse gut microbiota that likely contributes to several host-supportive services that include diet processing and nutrient provisioning. Loss of microbiome taxa and their associated metabolic functions as result of perturbations may result in loss of microbiome-level services and reduction of metabolic capacity. If metabolic functions are shared by multiple taxa (i.e., functional redundancy), including deeply divergent lineages, then the impact of taxon/function losses may be dampened. We examined to what degree alterations in phylotype diversity impact microbiome-level metabolic capacity. Feeding two nutritionally imbalanced diets to omnivorousPeriplaneta americanaover 8 weeks reduced the diversity of their phylotype-rich gut microbiomes by ~25% based on 16S rRNA gene amplicon sequencing, yet PICRUSt2-inferred metabolic pathway richness was largely unaffected due to their being polyphyletic. We concluded that the nonlinearity between taxon and metabolic functional losses is due to microbiome members sharing many well-characterized metabolic functions, with lineages remaining after perturbation potentially being capable of preventing microbiome “service outages” due to functional redundancy. IMPORTANCEDiet can affect gut microbiome taxonomic composition and diversity, but its impacts on community-level functional capabilities are less clear. Host health and fitness are increasingly being linked to microbiome composition and further modeling of the relationship between microbiome taxonomic and metabolic functional capability is needed to inform these linkages. Invertebrate animal models like the omnivorous American cockroach are ideal for this inquiry because they are amenable to various diets and provide high replicates per treatment at low costs and thus enabling rigorous statistical analyses and hypothesis testing. Microbiome taxonomic composition is diet-labile and diversity was reduced after feeding on unbalanced diets (i.e., post-treatment), but the predicted functional capacities of the post-treatment microbiomes were less affected likely due to the resilience of several abundant taxa surviving the perturbation as well as many metabolic functions being shared by several taxa. These results suggest that both taxonomic and functional profiles should be considered when attempting to infer how perturbations are altering gut microbiome services and possible host outcomes. 

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5. Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

   https://doi.org/10.1128/mBio.00145-21  

   Fuess, Lauren E.; den Haan, Stijn; Ling, Fei; Weber, Jesse N.; Steinel, Natalie C.; Bolnick, Daniel I. (January 2021, mBio)

   Rawls, John F.; McFall-Ngai, Margaret J. (Ed.)

   ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems. 

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