scholarly journals Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Host Immunity ◽  
Host Gene ◽  
Microbiota Composition ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Immune Genes

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.

scholarly journals Immune gene expression covaries with gut microbiome composition in stickleback

2020 ◽  
Author(s):  
Lauren Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Host Immunity ◽  
Host Gene ◽  
Microbiota Composition ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Immune Genes

ABSTRACTCommensal 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 immunity. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated to host gene expression. These families were all tightly correlated to 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 abundance of these taxons, 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.

scholarly journals The relationship between the gut microbiome and host gene expression: a review

2020 ◽  
Author(s):  
Robert G. Nichols ◽  
Emily R. Davenport
Keyword(s):  
Gene Expression ◽  
Gut Microbiome ◽  
Host Gene ◽  
Model Organisms ◽  
Host Gene Expression ◽  
Immune Development ◽  
Physiological Processes ◽  
Host Signaling ◽  
Important Regulator ◽  
The Relationship

AbstractDespite the growing knowledge surrounding host–microbiome interactions, we are just beginning to understand how the gut microbiome influences—and is influenced by—host gene expression. Here, we review recent literature that intersects these two fields, summarizing themes across studies. Work in model organisms, human biopsies, and cell culture demonstrate that the gut microbiome is an important regulator of several host pathways relevant for disease, including immune development and energy metabolism, and vice versa. The gut microbiome remodels host chromatin, causes differential splicing, alters the epigenetic landscape, and directly interrupts host signaling cascades. Emerging techniques like single-cell RNA sequencing and organoid generation have the potential to refine our understanding of the relationship between the gut microbiome and host gene expression in the future. By intersecting microbiome and host gene expression, we gain a window into the physiological processes important for fostering the extensive cross-kingdom interactions and ultimately our health.

scholarly journals Immune challenge reduces gut microbial diversity and triggers fertility-dependent gene expression changes in a social insect

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Matteo Antoine Negroni ◽  
Francisca H. I. D. Segers ◽  
Fanny Vogelweith ◽  
Susanne Foitzik
Keyword(s):  
Gene Expression ◽  
Life History ◽  
Immune System ◽  
Gut Microbiome ◽  
Life History Traits ◽  
Fat Body ◽  
Molecular Regulation ◽  
Immune Challenge ◽  
Microbiome Composition ◽  
Immune Genes

Abstract Background The gut microbiome can influence life history traits associated with host fitness such as fecundity and longevity. In most organisms, these two life history traits are traded-off, while they are positively linked in social insects. In ants, highly fecund queens can live for decades, while their non-reproducing workers exhibit much shorter lifespans. Yet, when fertility is induced in workers by death or removal of the queen, worker lifespan can increase. It is unclear how this positive link between fecundity and longevity is achieved and what role the gut microbiome and the immune system play in this. To gain insights into the molecular regulation of lifespan in social insects, we investigated fat body gene expression and gut microbiome composition in workers of the ant Temnothorax rugatulus in response to an experimental induction of fertility and an immune challenge. Results Fertile workers upregulated several molecular repair mechanisms, which could explain their extended lifespan. The immune challenge altered the expression of several thousand genes in the fat body, including many immune genes, and, interestingly, this transcriptomic response depended on worker fertility. For example, only fertile, immune-challenged workers upregulated genes involved in the synthesis of alpha-ketoglutarate, an immune system regulator, which extends the lifespan in Caenorhabditis elegans by down-regulating the TOR pathway and reducing oxidant production. Additionally, we observed a dramatic loss in bacterial diversity in the guts of the ants within a day of the immune challenge. Yet, bacterial density did not change, so that the gut microbiomes of many immune challenged workers consisted of only a single or a few bacterial strains. Moreover, the expression of immune genes was linked to the gut microbiome composition, suggesting that the ant host can regulate the microbiome in its gut. Conclusions Immune system flare-ups can have negative consequence on gut microbiome diversity, pointing to a previously underrated cost of immunity. Moreover, our results provide important insights into shifts in the molecular regulation of fertility and longevity associated with insect sociality.

scholarly journals Human papillomavirus 16 E2 regulates keratinocyte gene expression relevant to cancer and the viral life cycle

2018 ◽  
Author(s):  
Michael R Evans ◽  
Claire D James ◽  
Molly L Bristol ◽  
Tara J Nulton ◽  
Xu Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Radiation Therapy ◽  
Life Cycle ◽  
Innate Immune ◽  
Host Gene ◽  
Host Gene Expression ◽  
Immune Genes ◽  
E6 And E7 ◽  
Innate Immune Genes

AbstractHuman papillomaviruses (HPV) are causative agents in ano-genital and oropharyngeal cancers. The virus must reprogram host gene expression to promote infection, and E6 and E7 contribute to this via targeting of cellular transcription factors including p53 and pRb, respectively. The HPV16 E2 protein regulates host gene expression in U2OS cells and in this study we extend these observations into TERT immortalized oral keratinocytes (NOKs) that are capable of supporting late stages of the HPV16 life cycle. We observed repression of innate immune genes by E2 that are also repressed by the intact HPV16 genome in NOKs. RNA-seq data identified 167 up and 395 downregulated genes by E2; there was a highly significant overlap of the E2 regulated genes with those regulated by the intact HPV16 genome in the same cell type. siRNA targeting of E2 reversed repression of E2 targeted genes. The ability of E2 to repress innate immune genes was confirmed in an ano-genital immortalized keratinocyte cell line, N/Tert-1. We present analysis of data from The Cancer Genome Atlas (TCGA) for HPV16 positive and negative head and neck cancers (HNC) suggesting that E2 plays a role in regulation of the host genome in cancers. Patients with HPV16 positive HNC with a loss of E2 expression exhibit a worse clinical outcome and we discuss how this could, at least partially, be related to the loss of E2 host gene regulation.ImportanceHPV16 positive tumors that retain expression of E2 have a better clinical outcome than those that have lost E2 expression. It has been suggested that this is due to a loss of E2 repression of E6 and E7 expression but this is not supported by data from tumors where there is not more E6 and E7 expression in the absence of E2. Here we report that E2 regulates host gene expression and place this regulation in context of the HPV16 life cycle and HPV16 positive head and neck cancers (the majority of which retain E2 expression). We propose that this E2 function may play an important part in the increased response of HPV16 positive cancers to radiation therapy. Therefore, host gene regulation by E2 may be important for promotion of the HPV16 life cycle, and also for the response of HPV16 positive tumors to radiation therapy.

scholarly journals Interactions between the gut microbiome and host gene regulation in cystic fibrosis

2019 ◽  
Author(s):  
Gargi Dayama ◽  
Sambhawa Priya ◽  
David E. Niccum ◽  
Alexander Khoruts ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cystic Fibrosis ◽  
Gut Microbiome ◽  
Critical Role ◽  
Host Gene ◽  
Healthy Controls ◽  
Host Gene Expression ◽  
Microbe Interactions ◽  
Host Microbe Interactions

AbstractCystic Fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in theCFTRgene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have lead to markedly increased longevity of patients with CF, but new complications have emerged, such as early onset of colorectal cancer (CRC). Although the pathogenesis of CRC in CF remains unclear, altered host-microbe interactions might play a critical role. Here, we characterize the changes in the gut microbiome and host gene expression in colonic mucosa of CF patients relative to healthy controls. We find that CF patients show decreased microbial diversity, decreased abundance of taxa such asButyricimonas, Sutterella,and Ruminococcaceae, and increased abundance of other taxa, such as Actinobacteria and Firmicutes. We find that 1543 genes, includingCFTR,show differential expression in the colon of CF patients compared to healthy controls. Interestingly, we find that these genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of CRC, tumor suppression, cellular dysfunction, p53 and mTOR signaling pathways. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression, and identified CRC-related genes, includingLCN2andDUOX2,for which gene expression is correlated with the abundance of CRC-associated bacteria, such as Ruminococcaceae andVeillonella. Our results provide new insight into the role of host-microbe interactions in the etiology of CRC in CF.

scholarly journals Human Papillomavirus 16 E2 Regulates Keratinocyte Gene Expression Relevant to Cancer and the Viral Life Cycle

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Michael R. Evans ◽  
Claire D. James ◽  
Molly L. Bristol ◽  
Tara J. Nulton ◽  
Xu Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Radiation Therapy ◽  
Life Cycle ◽  
Innate Immune ◽  
Host Gene ◽  
Host Gene Expression ◽  
Human Papillomavirus 16 ◽  
Immune Genes ◽  
E6 And E7 ◽  
Innate Immune Genes

ABSTRACTHuman papillomaviruses (HPVs) are causative agents in ano-genital and oropharyngeal cancers. The virus must reprogram host gene expression to promote infection, and E6 and E7 contribute to this via the targeting of cellular transcription factors, including p53 and pRb, respectively. The HPV16 E2 protein regulates host gene expression in U2OS cells, and in this study, we extend these observations into telomerase reverse transcriptase (TERT) immortalized oral keratinocytes (NOKs) that are capable of supporting late stages of the HPV16 life cycle. We observed repression of innate immune genes by E2 that are also repressed by the intact HPV16 genome in NOKs. Transcriptome sequencing (RNA-seq) data identified 167 up- and 395 downregulated genes by E2; there was a highly significant overlap of the E2-regulated genes with those regulated by the intact HPV16 genome in the same cell type. Small interfering RNA (siRNA) targeting of E2 reversed the repression of E2-targeted genes. The ability of E2 to repress innate immune genes was confirmed in an ano-genital immortalized keratinocyte cell line, N/Tert-1. We present the analysis of data from The Cancer Genome Atlas (TCGA) for HPV16-positive and -negative head and neck cancers (HNC) suggesting that E2 plays a role in the regulation of the host genome in cancers. Patients with HPV16-positive HNC with a loss of E2 expression exhibited a worse clinical outcome, and we discuss how this could, at least partially, be related to the loss of E2 host gene regulation.IMPORTANCEHuman papillomavirus 16 (HPV16)-positive tumors that retain expression of E2 have a better clinical outcome than those that have lost E2 expression. It has been suggested that this is due to a loss of E2 repression of E6 and E7 expression, but this is not supported by data from tumors where there is not more E6 and E7 expression in the absence of E2. Here we report that E2 regulates host gene expression and place this regulation in the context of the HPV16 life cycle and HPV16-positive head and neck cancers (the majority of which retain E2 expression). We propose that this E2 function may play an important part in the increased response of HPV16-positive cancers to radiation therapy. Therefore, host gene regulation by E2 may be important for promotion of the HPV16 life cycle and also for the response of HPV16-positive tumors to radiation therapy.

scholarly journals Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding

2020 ◽  
Author(s):  
Jayanth Jawahar ◽  
Alexander McCumber ◽  
Colin Lickwar ◽  
Caroline Amoroso ◽  
Sol Gomez de la Torre Canny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ribosome Biogenesis ◽  
16S Rrna Gene Sequencing ◽  
Host Gene ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Host Genes

Abstract Background: The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary site of nutrient absorption and microbiome interaction, however our understanding of intestinal adaptations in host transcriptional programs and microbiome composition remains limited. Additionally, few studies on starvation have investigated intestinal responses to refeeding. The zebrafish presents unique opportunities to study the effects of long-term starvation and refeeding. We used RNA sequencing and 16S rRNA gene sequencing to uncover changes in the intestinal transcriptome and microbiome of zebrafish subjected to long-term starvation and refeeding compared to continuously fed controls. Results: Starvation over 21 days led to increased diversity and altered composition in the intestinal microbiome compared to fed controls, including relative increases in Vibrio and reductions in Plesiomonas bacteria. Starvation also led to significant alterations in host gene expression in the intestine, with distinct pathways affected at early and late stages of starvation. This included increases in the expression of ribosome biogenesis genes early in starvation, followed by decreased expression of genes involved in antiviral immunity and at later stages. These effects of starvation on the host transcriptome and microbiome were within 3 days after refeeding. Comparison with published datasets identified host genes responsive to starvation as well as high-fat feeding or microbiome colonization, and predicted host transcription factors that may be involved in starvation response. Conclusions: Long-term starvation induces progressive changes in microbiome composition and host gene expression in the zebrafish intestine, and these changes are rapidly reversed after refeeding. Our identification of bacterial taxa, host genes and host pathways involved in this response provides a framework for future investigation of the physiological and ecological mechanisms underlying intestinal adaptations to food restriction.

scholarly journals Dietary Patterns and Gut Microbiome Composition in a Large Population-Based Cohort

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 514-514
Author(s):  
Zhangling Chen ◽  
Djawad Radjabzadeh ◽  
Arfan Ikram ◽  
Andre Uitterlinden ◽  
Robert Kraaij ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Diet Quality ◽  
Gut Microbiome ◽  
Linear Models ◽  
Large Population ◽  
Alpha Diversity ◽  
Population Based ◽  
Shannon Index ◽  
Food Groups ◽  
Microbiome Composition

Abstract Objectives Effects of diet on health and disease risk may be mediated by changes in gut microbiome composition. Our aim was to examine associations between intake of food groups and overall diet quality with gut microbiome composition in a large population-based cohort. Methods We analyzed data of 1130 participants (median age 57 years) from the Rotterdam Study, a population-based cohort study in the Netherlands. We measured dietary intake using a 389-item FFQ, and assessed adherence to dietary guidelines for 14 food groups and combined into a diet quality score. We assessed gut microbiome composition using 16S rRNA gene sequencing. Data were available for 11 phyla, 19 classes, 25 orders, 44 families, and 184 genera. Alpha diversity was quantified by Shannon index and Richness, and beta diversity was qualified by Bray-Curtis distance. We used linear models to examine associations with Shannon index and Richness, Adonis function to examine variations of Bray-Curtis distance, and Multivariate Association with Linear Models to examine associations with gut microbial communities. Models were adjusted for technical covariates, energy intake, age, sex, physical activity, education, smoking and BMI. Results After adjustment, higher diet quality was associated with more alpha diversity and explained part of the variation in beta diversity (P < 0.001). Overall diet quality was associated with relative abundance of four families (Erysipelotrichaceae, Ruminococcaceae, Lachnospiraceae, Christensenellaceae), and 15 genera (Torques group, RuminococcaceaeUCG002, RuminococcaceaeUCG003, RuminococcaceaeUCG005, RuminococcaceaeUCG010, Xylanophilum group, Blautia, RuminococcaceaeNK4A214 group, Eligens group, Coprococcus3, Senegalimassilia, Lachnospira, Halliigroup, ChristensenellaceaeR7 group, Ventriosum group) (adjusted p: q < 0.05). Results were not explained by any single food group. Higher intake of fruits, vegetables, whole grains, and tea, and lower intake of red meat and alcohol were all related to microbiome composition. Replication analyses are ongoing. Conclusions Better overall diet quality may improve overall gut microbial diversity. Furthermore, diet quality may influence abundance of certain gut microbial communities, several of which have previously been linked to lower risk of metabolic and inflammatory diseases. Funding Sources N/A.

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