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

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.

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

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.


2020 ◽  
Author(s):  
Robert G. Nichols ◽  
Emily R. Davenport

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.


2020 ◽  
Author(s):  
Lauren Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang-Wei Liu ◽  
Nan Zhao ◽  
Yin-Na Su ◽  
Shan-Shan Chen ◽  
Xin-Jian He

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.


1990 ◽  
pp. 701-708 ◽  
Author(s):  
C. Sengupta-Gopalan ◽  
E. Estabrook ◽  
H. Gambliel ◽  
W. Nirunsuksiri ◽  
H. Richter

2011 ◽  
Vol 140 (5) ◽  
pp. S-663 ◽  
Author(s):  
Guillaume Dalmasso ◽  
Hang Thi Thu Nguyen ◽  
Yutao Yan ◽  
Hamed Laroui ◽  
Moiz A. Charania ◽  
...  

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