Environmental Sources of Bacteria and Genetic Variation in Behavior Influence Host-Associated Microbiota.
Ontology highlight
ABSTRACT:
SUBMITTER: Mushegian AA
PROVIDER: S-EPMC6450018 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.
| S-EPMC3475380 | biostudies-literature
Project description:Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNP-based approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A×B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A×B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies.
| S-EPMC4579341 | biostudies-literature
Project description:The host gut colonized enormous microbial community, which can be influenced by diet, diseases, behavior, age, gender, hereditary effects, and environmental factors. However, the relationship between gut microbiota and host genetic variation has not yet been elucidated. In this study, we chose five pheasant lineages-Ring-necked pheasant (RN), Manchurian pheasant (MX), Phasianus versicolor (PV), Shenhong pheasant (SP), and Melanistic mutant pheasant (MM)-to investigate the gut microbial composition of pheasants and its relationship with host genetic variation. Microbial classifications revealed 29 phyla and 241 genera presented in pheasants, with the dominant phylum of Firmicutes and the genus of Lactobacillus. Statistical analyses suggest that the relative abundance of 75 genera was significantly different among the five lineages. The most abundant genus carried by the RN and MM was Streptococcus, which was significantly lower in PV (p = 0.024). Conversely, Lactobacillus was the major genera in PV and MX. Moreover, the RN had the greatest microbial abundance, with a remarkably different microbial community than PV. The gut microbial diversity of PV was the lowest and diverged significantly from the RN and MX. Interestingly, the clustering of the MM and SP in the microbial dendrogram corresponded to their cluster in the host phylogeny. The host phylogenetic split of the RN, MX, and PV echoed their microbial distance. In conclusion, the congruence of host phylogeny and their gut microbial dendrograms implies that gut microbiota of pheasant lineages could reflect their host genetic variation.
| S-EPMC7438946 | biostudies-literature
Project description:Mitochondrial DNA copy number (mtDNA CN) has been shown to be highly heritable and associated with traits of interest in humans. However, studies are lacking in the literature for livestock species such as beef cattle. In this study, 2,371 individuals from a crossbred beef population comprising the Germplasm Evaluation program from the U.S. Meat Animal Research Center had samples of blood, leucocyte, or semen collected for low-pass sequencing (LPS) that resulted in both nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA) sequence reads. Mitochondrial DNA CN was estimated based on the ratio of mtDNA to nuDNA coverages. Genetic parameters for mtDNA CN were estimated from an animal model based on a genomic relationship matrix (~87K SNP from the nuDNA). Different models were used to test the effects of tissue, sex, age at sample collection, heterosis, and breed composition. Maternal effects, assessed by fitting a maternal additive component and by fitting eleven SNP on the mtDNA, were also obtained. As previously reported, mtDNA haplotypes were used to classify individuals into Taurine haplogroups (T1, T2, T3/T4, and T5). Estimates of heritability when fitting fixed effects in addition to the intercept were moderate, ranging from 0.11 to 0.31 depending on the model. From a model ignoring contemporary group, semen samples had the lowest mtDNA CN, as expected, followed by blood and leucocyte samples (P ≤ 0.001). The effect of sex and the linear and quadratic effects of age were significant (P ≤ 0.02) depending on the model. When significant, females had greater mtDNA CN than males. The effects of heterosis and maternal heterosis were not significant (P ≥ 0.47). The estimates of maternal and mtDNA heritability were near zero (≤0.03). Most of the samples (98%) were classified as haplogroup T3. Variation was observed in the mtDNA within Taurine haplogroups, which enabled the identification of 24 haplotypes. These results suggest that mtDNA CN is under nuclear genetic control and would respond favorably to selection.
| S-EPMC9150079 | biostudies-literature
Project description:Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance (P < 6.3 × 10-10 for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co-culturing with Staphylococcus epidermidis, chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction.
| S-EPMC9582029 | biostudies-literature
Project description:Cholera is still an important public health problem in several countries, including Thailand. In this study, a collection of clinical and environmental V. cholerae serogroup O1, O139, and non-O1/non-O139 strains originating from Thailand (1983 to 2013) was characterized to determine phenotypic and genotypic traits and to investigate the genetic relatedness. Using a combination of conventional methods and whole genome sequencing (WGS), 78 V. cholerae strains were identified. WGS was used to determine the serogroup, biotype, virulence, mobile genetic elements, and antimicrobial resistance genes using online bioinformatics tools. In addition, phenotypic antimicrobial resistance was determined by the minimal inhibitory concentration (MIC) test. The 78 V. cholerae strains belonged to the following serogroups O1: (n = 44), O139 (n = 16) and non-O1/non-O139 (n = 18). Interestingly, we found that the typical El Tor O1 strains were the major cause of clinical cholera during 1983-2000 with two Classical O1 strains detected in 2000. In 2004-2010, the El Tor variant strains revealed genotypes of the Classical biotype possessing either only ctxB or both ctxB and rstR while they harbored tcpA of the El Tor biotype. Thirty O1 and eleven O139 clinical strains carried CTXϕ (Cholera toxin) and tcpA as well four different pathogenic islands (PAIs). Beside non-O1/non-O139, the O1 environmental strains also presented chxA and Type Three Secretion System (TTSS). The in silico MultiLocus Sequence Typing (MLST) discriminated the O1 and O139 clinical strains from other serogroups and environmental strains. ST69 was dominant in the clinical strains belonging to the 7th pandemic clone. Non-O1/non-O139 and environmental strains showed various novel STs indicating genetic variation. Multidrug-resistant (MDR) strains were observed and conferred resistance to ampicillin, azithromycin, nalidixic acid, sulfamethoxazole, tetracycline, and trimethoprim and harboured variants of the SXT elements. For the first time since 1986, the presence of V. cholerae O1 Classical was reported causing cholera outbreaks in Thailand. In addition, we found that V. cholerae O1 El Tor variant and O139 were pre-dominating the pathogenic strains in Thailand. Using WGS and bioinformatic tools to analyze both historical and contemporary V. cholerae circulating in Thailand provided a more detailed understanding of the V. cholerae epidemiology, which ultimately could be applied for control measures and management of cholera in Thailand.
| S-EPMC5245877 | biostudies-literature
Project description:BackgroundGenetic predisposition and environmental influences are both important factors in the development of problematic behavior leading to substance use in adolescence. Involvement with delinquent peers also strongly predicts adolescent externalizing behavior. Several lines of evidence support a role of GABRA2 on externalizing behavior related to disinhibition. However, whether this genetic association is influenced by the environment such as peer behavior remains unknown.MethodsWe examined the moderating role of GABRA2 genetic variation on the socialization model of delinquent peer affiliation (at ages 12-14 years) on externalizing behavior (at ages 15-17 years) in the Michigan Longitudinal Study (MLS) adolescent sample. The sample consisted of 244 adolescents (75 females and 152 with at least one parent with a DSM-IV lifetime alcohol dependence/abuse diagnosis). Peer delinquent activity reported by the participant and teacher-reported adolescent externalizing behavior (Teacher Report Form (TRF) were assessed.ResultsNo main effect of the GABRA2 SNP rs279826, which tags a large haplotype, on externalizing behavior was observed. However, there was a statistically reliable GABRA2 × peer delinquency interaction. The effect of peer delinquent involvement on externalizing scores and the rule breaking subscale is significantly stronger for those with the GG genotype compared to A-carriers, whereas there was no effect of genotype on externalizing in the absence of peer delinquent involvement. No interaction was observed for the aggression subscale.ConclusionOur results suggest that the genetic effect of GABRA2 on externalizing behavior, more specifically on rule breaking is, at least in part, due to its effect on susceptibility to environmental exposure (i.e., peer delinquency).
| S-EPMC4212110 | biostudies-literature
Project description:In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.
| S-EPMC2973891 | biostudies-other
Project description:Different sources of epigenetic changes can increase the range of phenotypic options. Environmentally induced epigenetic changes and stochastic epimutations are, respectively, associated with phenotypic plasticity and diversifying bet-hedging. Their relative contribution is thus expected to reflect the capacity of a genotype to face distinct changes since these strategies are differentially selected according to environmental uncertainty. To test this hypothesis, we assessed the sources of epigenetic changes on clonal fish from predictable (lakes) or unpredictable (intermittent streams) environments. DNA methylation of clones from natural conditions revealed contrasting contribution of environmentally induced versus stochastic changes according to their origins. These differences were validated in common garden experiments. Consistent with theoretical models, distinct sources of epigenetic variation prevail according to the environmental uncertainty. However, both sources act conjointly, suggesting that plasticity and random processes are complementary strategies. This represents a rigorous approach for further exploring the capacity of organisms to respond to environmental conditions.
| S-EPMC4984500 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory disorders of the gastrointestinal tract with complex etiology and no strategies for complete cure. IBD are often complicated by mental disorders like anxiety and depression, indicating substantial shifts in the microbiota gut-brain axis. However, the mechanisms connecting IBD to mental diseases are still under debate. Here we use Muc2 knockout mouse model of chronic colitis to uncouple the effects of the intestinal microbiota on host behavior from chronic inflammation in the gut. Muc2 knockout male mice exhibit high exploratory activity, reduced anxiety-related behaviors, impaired sensorimotor gating, and altered social preference towards males and females. Microbial transfer to wild-type mice via littermate co-housing shows that colitis-associated microbiota rather than inflammation per se defines behavioral features in Muc2 colitis model. Metagenomic profiling and combination of antibiotic treatments revealed that bacterial species Akkermansia muciniphila is associated with the behavioral phenotype in mutants, and that its intestinal abundance correlates with social preference towards males. Metabolomic analysis together with pharmacological inhibition of Gly and NMDA receptors helped us to determine that brain glycine is responsible for the behavioral phenotype in Muc2 mice. Blood and brain metabolic profiles suggest that microbiota-dependent changes in choline metabolism might be involved in regulation of central glycine neurotransmission. Taken together, our data demonstrates that colitis-associated microbiota controls anxiety, sensorimotor gating and social behavior via metabolic regulation of the brain glycinergic system, providing new venues to combat neurological complications of IBD.
| S-EPMC9522854 | biostudies-literature