Host genetic variation in mucosal immunity pathways influences the upper airway microbiome

ABSTRACTThe degree to which host genetic variation can modulate microbial communities in humans remains an open question. Here we performed a genetic mapping study of the microbiome in two accessible upper airway sites, the nasopharynx and the nasal vestibule, during two seasons in 144 adult members of a founder population of European decent. We estimated the relative abundances (RAs) of genus level bacteria from 16S rRNA gene sequences and examined associations with 148,653 genetic variants (linkage disequilibrium [LD] r2 < 0.5) selected from among all common variants discovered in genome sequences in this population. We identified 37 microbiome quantitative trait loci (mbQTLs) that showed evidence of association with the RAs of 22 genera (q < 0.05), and were enriched for genes in mucosal immunity pathways. The most significant association was between the RA of Dermacoccus (phylum Actinobacteria) and a variant 8kb upstream of TINCR (rs117042385; p = 1.61⨯10−8; q = 0.002), a long non-coding RNA that binds to peptidoglycan recognition protein 3 (PGLYRP3) mRNA, a gene encoding a known antimicrobial protein. A second association was between a missense variant in PGLYRP4 (rs3006458) and the RA of an unclassified genus of family Micrococcaceae (phylum Actinobacteria) (p = 5.10⨯10−7; q = 0.032). Our findings provide evidence of host genetic influences on upper airway microbial composition in humans, and implicate mucosal immunity genes in this relationship.

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Host genetic variation in mucosal immunity pathways influences the upper airway microbiome

Microbiome ◽

10.1186/s40168-016-0227-5 ◽

2017 ◽

Vol 5 (1) ◽

Cited By ~ 31

Author(s):

Catherine Igartua ◽

Emily R. Davenport ◽

Yoav Gilad ◽

Dan L. Nicolae ◽

Jayant Pinto ◽

...

Keyword(s):

Genetic Variation ◽

Mucosal Immunity ◽

Upper Airway ◽

Airway Microbiome ◽

Host Genetic

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The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes

10.1101/2020.07.19.20157404 ◽

2020 ◽

Author(s):

Andrew T Hale ◽

Dan Zhou ◽

Rebecca L Sale ◽

Lisa Bastarache ◽

Liuyang Wang ◽

...

Keyword(s):

Genetic Variation ◽

Infectious Diseases ◽

Molecular Mechanisms ◽

Causal Effect ◽

Association Studies ◽

Rrna Gene ◽

Pathogen Invasion ◽

Gene Level ◽

Host Genetic ◽

Cellular Phenotypes

Infectious diseases (ID) represent a significant proportion of morbidity and mortality across the world. Host genetic variation is likely to contribute to ID risk and downstream clinical outcomes, but there is a need for a genetics-anchored framework to decipher molecular mechanisms of disease risk, infer causal effect on potential complications, and identify instruments for drug target discovery. Here we perform transcriptome-wide association studies (TWAS) of 35 clinical ID traits in a cohort of 23,294 individuals, identifying 70 gene-level associations with 26 ID traits. Replication in two large-scale biobanks provides additional support for the identified associations. A phenome-scale scan of the 70 gene-level associations across hematologic, respiratory, cardiovascular, and neurologic traits proposes a molecular basis for known complications of the ID traits. Using Mendelian Randomization, we then provide causal support for the effect of the ID traits on adverse outcomes. The rich resource of genetic information linked to serologic tests and pathogen cultures from bronchoalveolar lavage, sputum, sinus/nasopharyngeal, tracheal, and blood samples (up to 7,699 positive pathogen cultures across 92 unique genera) and a large catalog of genome-wide associations of microbiome variation generated from phylogenetic analysis of 16S rRNA gene sequences are developed here into a platform to interrogate the genetic basis of compartment-specific infection and colonization. To accelerate insights into cellular mechanisms, we develop a TWAS repository of gene-level associations in a broad collection of human tissues with 79 pathogen-exposure induced cellular phenotypes as a discovery and replication platform. Cellular phenotypes of infection by 8 pathogens included pathogen invasion, intercellular spread, cytokine production, and pyroptosis. These rich datasets will facilitate mechanistic insights into the role of host genetic variation on ID risk and pathophysiology, with important implications for our molecular understanding of potentially severe phenotypic outcomes.

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HOMINID: A framework for identifying associations between host genetic variation and microbiome composition

10.1101/081323 ◽

2016 ◽

Cited By ~ 2

Author(s):

Joshua Lynch ◽

Karen Tang ◽

Sambhawa Priya ◽

Joanna Sands ◽

Margaret Sands ◽

...

Keyword(s):

Genetic Variation ◽

Sequence Data ◽

Synthetic Data ◽

Simulated Data ◽

Real Data ◽

Taxonomic Composition ◽

Rrna Gene ◽

Microbiome Composition ◽

Link Type ◽

Host Genetic

AbstractRecent studies have uncovered a strong effect of host genetic variation on the composition of host-associated microbiota. Here, we present HOMINID, a computational approach based on Lasso linear regression, that given host genetic variation and microbiome composition data, identifies host SNPs that are correlated with microbial taxa abundances. Using simulated data we show that HOMINID has accuracy in identifying associated SNPs, and performs better compared to existing methods. We also show that HOMINID can accurately identify the microbial taxa that are correlated with associated SNPs. Lastly, by using HOMINID on real data of human genetic variation and microbiome composition, we identified 13 human SNPs in which genetic variation is correlated with microbiome taxonomic composition across body sites. In conclusion, HOMINID is a powerful method to detect host genetic variants linked to microbiome composition, and can facilitate discovery of mechanisms controlling host-microbiome interactions.Availability and implementationSoftware, code, tutorial, installation and setup details, and synthetic data are available in the project homepage: https://github.com/blekhmanlab/hominid.Real dataset used here is from Blekhman et al. (Blekhman et al. 2015); 16S rRNA gene sequence data and OTU tables are available on the HMP DACC website (www.hmpdacc.org), and host genetic data are deposited in dbGaP under project number phs000228.

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Signs of host genetic regulation in the microbiome composition in cattle

10.1101/100966 ◽

2017 ◽

Cited By ~ 1

Author(s):

O. Gonzalez-Recio ◽

I. Zubiria ◽

A. García-Rodríguez ◽

A. Hurtado ◽

R. Atxaerandio

Keyword(s):

Genetic Control ◽

Relative Abundance ◽

Complex Traits ◽

Genetic Background ◽

Snp Markers ◽

Rrna Gene ◽

Microbial Composition ◽

Genetic Link ◽

Microbiome Composition ◽

Host Genetic

ABSTRACTPrevious studies have revealed certain genetic control by the host over the microbiome composition, although in many species the host genetic link controlling microbial composition is yet unknown. This potential association is important in livestock to study all factors and interactions that rule the effect of the microbiome in complex traits. This report aims to study whether the host genotype exerts any genetic control on the microbiome composition of the rumen in cattle. Data on 16S and 18S rRNA gene-based analysis of the rumen microbiome in 18 dairy cows from two different breeds (Holstein and Brown Swiss) were used. The effect of the genetic background of the animal (through the breed and Single Nucleotide Polymorphisms; SNP) on the relative abundance (RA) of archaea, bacteria and ciliates (with average relative abundance per breed >0.1%) was analysed using Bayesian statistics. In total, 13 genera were analysed for bacteria (5), archaea (1), and ciliates (7). All these bacteria and archaea genera showed association to the host genetic background both for breed and SNP markers, except RA for the generaButyrivibrioandRuminococcusthat showed association with the SNP markers but not with the breed composition. Relative abundance of 57% (4/7) of ciliate analysed showed to be associated to the genetic background of the host. This host genetic link was observed in some genus ofTrichostomatiafamily. For instance, the breed had a significant effect onIsotricha,OphryoscolexandPolyplastron, and the SNP markers onEntodinium,OphryoscolexandPolyplastron. In total, 77% (10/13) of microbes analysed showed to be associated to the host genetic background (either by breed or SNP genotypes). Further, the results showed a significant association between DGAT1, ACSF3, AGPAT3 and STC2 genes with the relative abundancePrevotellagenus with a false discovery rate lower than 15%. The results in this study support the hypothesis and provide some evidence that there exist a host genetic component in cattle that can partially regulate the composition of the microbiome.

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Population bottlenecks constrain microbiome diversity and host genetic variation impeding fitness

10.1101/2021.07.04.450854 ◽

2021 ◽

Author(s):

Michael Oersted ◽

Erika Yashiro ◽

Ary A Hoffmann ◽

Torsten Nygaard Kristensen

Keyword(s):

Genetic Variation ◽

Microbial Diversity ◽

Focal Point ◽

Host Population ◽

Rrna Gene ◽

Population Bottlenecks ◽

Biodiversity Crisis ◽

Microbiome Diversity ◽

Host Genetic ◽

Microbial Symbionts

It is becoming increasingly clear that microbial symbionts influence key aspects of their host's fitness, and vice versa. This may fundamentally change our thinking about how microbes and hosts interact in influencing fitness and adaptation to changing environments. Here we explore how reductions in population size commonly experienced by threatened species influence microbiome diversity. Fitness consequences of such reductions are normally interpreted in terms of a loss of genetic variation and increase in inbreeding depression due to a loss of heterozygosity. However, fitness effects might also be mediated through microbiome diversity, e.g. if functionally important microbes are lost. Here we utilise Drosophila melanogaster lines with different histories of population bottlenecks to explore these questions. The lines were phenotyped for egg-to-adult viability and their genomes sequenced to estimate genetic variation. The bacterial 16S rRNA gene was amplified in these lines to investigate microbial diversity. We found that 1) host population bottlenecks constrained microbiome richness and diversity, 2) core microbiomes of hosts with low genetic variation were constituted from subsets of microbiomes found in flies with higher genetic variation, 3) both microbiome diversity and host genetic variation contributed to host population fitness, 4) connectivity and robustness of bacterial networks increased with higher host genetic variation, and 5) reduced microbial diversity is associated with weaker evolutionary responses in stressful environments. These findings suggest that population bottlenecks reduce hologenomic variation (in combined host and microbial genomes). Thus while the current biodiversity crisis focuses on population sizes and genetic variation of eukaryotes, an additional focal point should be the microbial diversity carried by the eukaryotes, which in turn may influence host fitness and adaptability with consequences for the persistence of populations.

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Diversity, Composition and Functional Inference of Gut Microbiota in Indian Cabbage white Pieris canidia (Lepidoptera: Pieridae)

Life ◽

10.3390/life10110254 ◽

2020 ◽

Vol 10 (11) ◽

pp. 254

Author(s):

Ying Wang ◽

Jianqing Zhu ◽

Jie Fang ◽

Li Shen ◽

Shuojia Ma ◽

...

Keyword(s):

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Adult Survival ◽

Rrna Gene ◽

Life Stages ◽

Microbial Composition ◽

Significant Difference ◽

Functional Inference ◽

Rrna Gene Sequencing ◽

Insect Fitness

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.

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Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

Scientific Reports ◽

10.1038/s41598-021-83284-z ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Katherine A. Partrick ◽

Anna M. Rosenhauer ◽

Jérémie Auger ◽

Amanda R. Arnold ◽

Nicole M. Ronczkowski ◽

...

Keyword(s):

Social Stress ◽

Bifidobacterium Longum ◽

Social Defeat ◽

Lactobacillus Helveticus ◽

Rrna Gene ◽

Social Avoidance ◽

Social Defeat Stress ◽

Microbial Structure ◽

Microbial Composition ◽

Anti Inflammatory

AbstractSocial stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.

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Host reproductive cycle influences the pouch microbiota of wild southern hairy-nosed wombats (Lasiorhinus latifrons)

Animal Microbiome ◽

10.1186/s42523-021-00074-8 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Sesilje Weiss ◽

David Taggart ◽

Ian Smith ◽

Kristofer M. Helgen ◽

Raphael Eisenhofer

Keyword(s):

Microbial Community ◽

Reproductive Cycle ◽

Tammar Wallaby ◽

The Body ◽

Rrna Gene ◽

Microbial Composition ◽

Birth Canal ◽

Gram Positive Bacteria ◽

Rigorous Framework ◽

The 16S Rrna Gene

Abstract Background Marsupials are born much earlier than placental mammals, with most crawling from the birth canal to the protective marsupium (pouch) to further their development. However, little is known about the microbiology of the pouch and how it changes throughout a marsupial’s reproductive cycle. Here, using stringent controls, we characterized the microbial composition of multiple body sites from 26 wild Southern Hairy-nosed Wombats (SHNWs), including pouch samples from animals at different reproductive stages. Results Using qPCR of the 16S rRNA gene we detected a microbial community in the SHNW pouch. We observed significant differences in microbial composition and diversity between the body sites tested, as well as between pouch samples from different reproductive stages. The pouches of reproductively active females had drastically lower microbial diversity (mean ASV richness 19 ± 8) compared to reproductively inactive females (mean ASV richness 941 ± 393) and were dominated by gram positive bacteria from the Actinobacteriota phylum (81.7–90.6%), with the dominant families classified as Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, and Dietziaceae. Three of the five most abundant sequences identified in reproductively active pouches had closest matches to microbes previously isolated from tammar wallaby pouches. Conclusions This study represents the first contamination-controlled investigation into the marsupial pouch microbiota, and sets a rigorous framework for future pouch microbiota studies. Our results indicate that SHNW pouches contain communities of microorganisms that are substantially altered by the host reproductive cycle. We recommend further investigation into the roles that pouch microorganisms may play in marsupial reproductive health and joey survival.

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Ultrafine particles altered gut microbial population and metabolic profiles in a sex-specific manner in an obese mouse model

Scientific Reports ◽

10.1038/s41598-021-85784-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kundi Yang ◽

Mengyang Xu ◽

Jingyi Cao ◽

Qi Zhu ◽

Monica Rahman ◽

...

Keyword(s):

Ultrafine Particles ◽

Microbial Population ◽

Phosphate Buffer Solution ◽

Biodiesel Fuel ◽

Control Group ◽

Obese Mouse ◽

Rrna Gene ◽

Obese Mice ◽

Microbial Composition ◽

Increased Risk

AbstractEmerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (80:20 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography–mass spectrometry (LC–MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p < 0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).

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Metagenomic, Metabolomic, and Functional Evaluation of Kimchi Broth Treated with Light-Emitting Diodes (LEDs)

Metabolites ◽

10.3390/metabo11080472 ◽

2021 ◽

Vol 11 (8) ◽

pp. 472

Author(s):

Yeong-Ji Oh ◽

Ye-Rin Park ◽

Jungil Hong ◽

Do-Yup Lee

Keyword(s):

Amplicon Sequencing ◽

Taxonomic Composition ◽

Metabolic Phenotype ◽

Rrna Gene ◽

Functional Evaluation ◽

Initial Condition ◽

Microbial Composition ◽

Light Emitting ◽

Blue Led ◽

Red Led

The light-emitting diode (LED) has been widely used in the food industry, and its application has been focused on microbial sterilization, specifically using blue-LED. The investigation has been recently extended to characterize the biotic and abiotic (photodynamic) effects of different wavelengths. Here, we investigated LED effects on kimchi fermentation. Kimchi broths were treated with three different colored-LEDs (red, green, and blue) or kept in the dark as a control. Multiomics was applied to evaluate the microbial taxonomic composition using 16S rRNA gene amplicon sequencing, and the metabolomic profiles were determined using liquid chromatography–Orbitrap mass spectrometry. Cell viability was tested to determine the potential cytotoxicity of the LED-treated kimchi broths. First, the amplicon sequencing data showed substantial changes in taxonomic composition at the family and genus levels according to incubation (initial condition vs. all other groups). The differences among the treated groups (red-LED (RLED), green-LED (GLED), blue-LED (BLED), and dark condition) were marginal. The relative abundance of Weissella was decreased in all treated groups compared to that of the initial condition, which coincided with the decreased composition of Lactobacillus. Compositional changes were relatively high in the GLED group. Subsequent metabolomic analysis indicated a unique metabolic phenotype instigated by different LED treatments, which led to the identification of the LED treatment-specific and common compounds (e.g., luteolin, 6-methylquinoline, 2-hydroxycinnamic acid, and 9-HODE). These results indicate that different LED wavelengths induce characteristic alterations in the microbial composition and metabolomic content, which may have applications in food processing and storage with the aim of improving nutritional quality and the safety of food.

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