Plant genetic effects on microbial hubs impact host fitness in repeated field trials.

Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200 Arabidopsis thaliana genotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes.

Microbiota composition modulates inflammation and neointimal hyperplasia after arterial angioplasty.

BACKGROUND: Neointimal hyperplasia is a major contributor to restenosis after arterial interventions, but the genetic and environmental mechanisms underlying the variable propensity for neointimal hyperplasia between individuals, including the role of commensal microbiota, are not well understood. We sought to characterize how shifting the microbiome using cage sharing and bedding mixing between rats with differing restenosis phenotypes after carotid artery balloon angioplasty could alter arterial remodeling. METHODS: We co-housed and mixed bedding between genetically distinct rats (Lewis [LE] and Sprague-Dawley [SD]) that harbor different commensal microbes and that are known to have different neointimal hyperplasia responses to carotid artery balloon angioplasty. Sequencing of the 16S ribosomal RNA gene was used to monitor changes in the gut microbiome. RESULTS: There were significant differences in neointimal hyperplasia between non-co-housed LE and SD rats 14 days after carotid artery angioplasty (mean intima + media [I + M] area, 0.117 ± 0.014 mm2 LE vs 0.275 ± 0.021 mm2 SD; P < .001) that were diminished by co-housing. Co-housing also altered local adventitial Ki67 immunoreactivity, local accumulation of leukocytes and macrophages (total and M2), and interleukin 17A concentration 3 days after surgery in each strain. Non-co-housed SD and LE rats had microbiomes distinguished by both weighted (P = .012) and unweighted (P < .001) UniFrac beta diversity distances, although without significant differences in alpha diversity. The difference in unweighted beta diversity between the fecal microbiota of SD and LE rats was significantly reduced by co-housing. Operational taxonomic units that significantly correlated with average I + M area include Parabacteroides distasonis, Desulfovibrio, Methanosphaera, Peptococcus, and Prevotella. Finally, serum concentrations of microbe-derived metabolites hydroxyanthranilic acid and kynurenine/tryptophan ratio were significantly associated with I + M area in both rat strains independent of co-housing. CONCLUSIONS: We describe a novel mechanism for how microbiome manipulations affect arterial remodeling and the inflammatory response after arterial injury. A greater understanding of the host inflammatory-microbe axis could uncover novel therapeutic targets for the prevention and treatment of restenosis.

Inducible phenotypic plasticity in plants regulates aquatic ecosystem functioning.

Differences among individuals within species affect community and ecosystem processes in many systems, and may rival the importance of differences between species. Intraspecific variation consists of both plastic and genetic components that are regulated by different processes and operate on different time scales. Therefore, probing which mechanisms can affect traits sufficiently strongly to affect ecosystem processes is fundamental to understanding the consequences of individual variation. We find that a dominant deciduous tree of Pacific Northwest riparian ecosystems, red alder, exhibits strong and synergistic responses to nutrient resources and herbivory stress. These induced responses, which include shifting nutrient and plant secondary metabolite composition, have cascading effects on aquatic ecosystem function. Defense responses suppress leaf litter decomposition in small streams, thus altering the rate of energy capture for one of the most abundant terrestrial carbon sources entering aquatic systems. We find that alder responses to herbivory stress largely depend on availability of soil nutrients, with modification of the highly cytotoxic diarylheptanoid group of secondary metabolites being favored in nutrient-poor environments and modification of the typically dose-dependent ellagitannins being favored in nutrient-rich environments. Importantly, these findings identify traits for herbivore resistance in alder trees and demonstrate that plastic responses occurring within a species and over short time scales substantially alter a key function of an adjacent ecosystem. Furthermore, demonstrating plasticity among alder secondary metabolites lends insight into this system, in which decomposer communities are known to adjust to the secondary chemistry of local alder trees to facilitate rapid decomposition of locally derived leaf litter.

Coselected genes determine adaptive variation in herbivore resistance throughout the native range of Arabidopsis thaliana.

The "mustard oil bomb" is a major defense mechanism in the Brassicaceae, which includes crops such as canola and the model plant Arabidopsis thaliana. These plants produce and store blends of amino acid-derived secondary metabolites called glucosinolates. Upon tissue rupture by natural enemies, the myrosinase enzyme hydrolyses glucosinolates, releasing defense molecules. Brassicaceae display extensive variation in the mixture of glucosinolates that they produce. To investigate the genetics underlying natural variation in glucosinolate profiles, we conducted a large genome-wide association study of 22 methionine-derived glucosinolates using A. thaliana accessions from across Europe. We found that 36% of among accession variation in overall glucosinolate profile was explained by genetic differentiation at only three known loci from the glucosinolate pathway. Glucosinolate-related SNPs were up to 490-fold enriched in the extreme tail of the genome-wide [Formula: see text] scan, indicating strong selection on loci controlling this pathway. Glucosinolate profiles displayed a striking longitudinal gradient with alkenyl and hydroxyalkenyl glucosinolates enriched in the West. We detected a significant contribution of glucosinolate loci toward general herbivore resistance and lifetime fitness in common garden experiments conducted in France, where accessions are enriched in hydroxyalkenyls. In addition to demonstrating the adaptive value of glucosinolate profile variation, we also detected long-distance linkage disequilibrium at two underlying loci, GS-OH and GS-ELONG. Locally cooccurring alleles at these loci display epistatic effects on herbivore resistance and fitness in ecologically realistic conditions. Together, our results suggest that natural selection has favored a locally adaptive configuration of physically unlinked loci in Western Europe.

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice.

The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1α, PGC-1ß, and PDGFRα in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype.

Intraspecific leaf chemistry drives locally accelerated ecosystem function in aquatic and terrestrial communities.

Resource patchiness influences consumer foraging, movement, and physiology. Fluxes across ecosystem boundaries can extend these effects to otherwise distinct food webs. Intraspecific diversity of these cross-ecosystem subsidies can have large consequences for recipient systems. Here, we show intraspecific variation in leaf defensive chemistry of riparian trees drives local adaptation among terrestrial and riverine decomposers that consume shed leaf litter. We found extensive geographic structuring of ellagitannins, diarylheptanoids, and flavonoids in red alder trees. Ellagitannins, particularly those with strong oxidative activity, drive aquatic leaf decomposition. Further, spatial variation in these leaf components drives local ecological matching: in experiments using artificial food sources distinguished only by the chemical content of individual trees, we found decomposers both on land and in rivers more quickly consumed locally derived food sources. These results illustrate that terrestrial processes can change the chemistry of cross-ecosystem subsidies in ways that ultimately alter ecosystem function in donor and recipient systems.

Genome-wide association mapping within a local Arabidopsis thaliana population more fully reveals the genetic architecture for defensive metabolite diversity.

A paradoxical finding from genome-wide association studies (GWAS) in plants is that variation in metabolite profiles typically maps to a small number of loci, despite the complexity of underlying biosynthetic pathways. This discrepancy may partially arise from limitations presented by geographically diverse mapping panels. Properties of metabolic pathways that impede GWAS by diluting the additive effect of a causal variant, such as allelic and genetic heterogeneity and epistasis, would be expected to increase in severity with the geographical range of the mapping panel. We hypothesized that a population from a single locality would reveal an expanded set of associated loci. We tested this in a French Arabidopsis thaliana population (less than 1 km transect) by profiling and conducting GWAS for glucosinolates, a suite of defensive metabolites that have been studied in depth through functional and genetic mapping approaches. For two distinct classes of glucosinolates, we discovered more associations at biosynthetic loci than the previous GWAS with continental-scale mapping panels. Candidate genes underlying novel associations were supported by concordance between their observed effects in the TOU-A population and previous functional genetic and biochemical characterization. Local populations complement geographically diverse mapping panels to reveal a more complete genetic architecture for metabolic traits. This article is part of the theme issue 'Genetic basis of adaptation and speciation: from loci to causative mutations'.