Query: epigenome microbiome association

title: Association of colorectal carcinogenesis pathway with life style and intestinal microbiome based on the genome and epigenome abnormalities.

title: Clinical Relevance of Genetic Factors in Pulmonary Diseases
abstract: Many pulmonary disease genotypes have been identified in genomewide association studies using microarray technology. These genetic variants are relatively common but generally explain little about the heritability of disease, a phenomenon known as "missing heritability." This suggests that a genomic approach alone might not be enough to determine the phenotype and heritability of pulmonary diseases. Since the airway is continuously exposed to various environmental factors, the gene environment interaction is extremely important in the pathogenesis of pulmonary diseases. However, the mechanisms by which environmental factors contribute to the heritability and pathological development of pulmonary diseases remain unknown. Recently, it has been reported that not only the genome but also the epigenome and microbiome are involved in the determination of disease susceptibility and phenotype. Recent advances in analytical techniques have yielded enormous quantities of diverse types of individual biological information, including genomic, epigenomic, transcriptomic, proteomic, metabolomic, and microbiomic data. Using this vast array of biometric information, new pulmonary disease phenotypes will be identified and could be used to develop personalized medicines for patients with pulmonary diseases in the future. This review provides an overview of the current knowledge of the genomic medicine for better understanding of the heritability of pulmonary disease.

title: Epigenetic Regulation of Intestinal Fibrosis
abstract: Genome wide association studies have identified over 200 risk loci associated with Inflammatory Bowel Diseases (IBD) Crohn's disease and Ulcerative colitis. These genetic factors, however, account for only a small proportion of genetic inheritability of disease. Our understanding of the pathogenesis of IBD has evolved and currently is thought to occur through the interaction between the host genome and their intestinal microbiome and metabolome with the innate and adaptive immune responses. Genetic risk alone, however, predicts only 25% of disease indicating that other factors including the intestinal environment can shape the epigenome and also independently confer heritable risk to patients. Epigenetic modifications regulate gene expression and protein production and play critical roles in shaping the intestinal immune response, mucosal homeostasis, and the wound healing process. Analysis of the genetic risk in patients with Crohn's disease combined with epigenetic marks reveals regulatory mechanisms that affect gene expression and disease phenotype. This chapter will focus on what is known about the alteration in the epigenome in Crohn's disease and the mechanisms by which epigenetic risk factors determine development of fibrosis in Crohn's disease. Studies of the epigenome have highlighted new therapeutic targets for therapeutic intervention of the development and progression of fibrosis.

title: Clinical Development of Genomic Medicine in Pulmonary Diseases: Are Genetic Factors Enough to Determine the Phenotype and Inheritance of Pulmonary Diseases?
abstract: Many pulmonary disease genotypes have been identified in genome wide association studies using microarray technology. These genetic variants are relatively common but generally explain little about the heritability of disease, a phenomenon known as "missing heritability." This suggests that a genomic approach alone might not be enough to determine the phenotype and heritability of pulmonary diseases. Since the airway is continuously exposed to various environmental factors, the gene environment interaction is extremely important in the pathogenesis of pulmonary diseases. However, the mechanisms by which environmental factors contribute to the heritability and pathological development of pulmonary diseases remain unknown. Recently, it has been reported that not only the genome but also the epigenome and microbiome are involved in the determination of disease susceptibility and phenotype. Recent advances in analytical techniques have yielded enormous quantities of diverse types of individual biological information, including genomic, epigenomic, transcriptomic, proteomic, metabolomic, and microbiomic data. Using this vast array of biometric information, new pulmonary disease phenotypes will be identified and could be used to develop personalized medicines for patients with pulmonary diseases in the future. This review provides an overview of the current knowledge of the genomic medicine for better understanding of the heritability of pulmonary disease.

title: Epigenome Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease
abstract: Preterm birth is the leading cause of infant morbidity and mortality. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease affecting primarily premature infants, which can be lethal. Microbial intestinal colonization may alter epigenetic signatures of the immature gut establishing inflammatory and barrier properties predisposing to the development of NEC. We hypothesize that a crosstalk exists between the epigenome of the host and the initial intestinal colonizing microbiota at critical neonatal stages. By exposing immature enterocytes to probiotic and pathogenic bacteria, we showed over 200 regions of differential DNA modification, which were specific for each exposure. Reciprocally, using a mouse model of prenatal exposure to dexamethasone we demonstrated that antenatal treatment with glucocorticoids alters the epigenome of the host. We investigated the effects on the expression profiles of genes associated with inflammatory responses and intestinal barrier by qPCR based gene expression array and verified the DNA modification changes in 5 candidate genes by quantitative methylation specific PCR (qMSP) Importantly, by 16S RNA sequencing based phylogenetic analysis of intestinal bacteria in mice at 2 weeks of life, we showed that epigenome changes conditioned early microbiota colonization leading to differential bacterial colonization at different taxonomic levels. Our findings support a novel conceptual framework in which epigenetic changes induced by intrauterine influences affect early microbial colonization and intestinal development, which may alter disease susceptibility.

title: Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development
abstract: In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer related deaths globally. Hence, a more in depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

title: Meta analysis of human genome microbiome association studies: the MiBioGen consortium initiative
abstract: BackgroundIn recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture.ResultsHere, we announce the MiBioGen consortium initiative, which has assembled 18 population level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta analyses of genome wide associations. All pipeline and summary statistics results will be shared using public data repositories.ConclusionWe present the largest consortium to date devoted to microbiota GWAS. We have adapted our analytical pipelines to suit multi cohort analyses and expect to gain insight into host microbiota cross talk at the genome wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

title: Pldist: Ecological Dissimilarities for Paired and Longitudinal Microbiome Association Analysis
abstract: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter subject variability. Statistical methods for analyzing such datasets are scarce.  We introduce a paired UniFrac dissimilarity that summarizes within individual (or within pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs) This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.  The R package pldist is available on GitHub at https:/github.com/aplantin/pldist.

title: Deciphering the Human Gut Microbiome of Urolithin Metabotypes: Association with Enterotypes and Potential Cardiometabolic Health Implications
abstract: The gut microbiota ellagitannin metabolizing phenotypes (i.e. urolithin metabotypes [UMs] are proposed as potential cardiovascular disease (CVD) risk biomarkers because the host blood lipid profile is reported to be associated with specific UMs. However, the link for this association remains unknown so far.  The gut microbiome of 249 healthy individuals is analyzed using 16S rDNA sequencing analysis. Individuals are also stratified by UMs (UM A, UM B, and UM 0) and enterotypes (Bacteroides, Prevotella, and Ruminococcus) Associations of UMs discriminating bacteria with CVD risk markers are investigated. Distribution and gut microbiota composition of UMs and enterotypes are not coincident. Almost half of the discriminating genera between UM A and UM B belongs to the Coriobacteriaceae family. UM B individuals present higher blood cholesterol levels and higher alpha diversity, including Coriobacteriaceae family, than those of UM A. Coriobacteriaceae, whose abundance is the highest in UM B, is positively correlated with total cholesterol, LDL cholesterol, and body mass index.  Results herein suggest that the family Coriobacteriaceae could be a link between individuals' UMs and their blood cholesterol levels. Further research is needed to explore the mechanisms of the host metabolic phenotype, including cholesterol excretion products, to modulate this bacterial family.

title: Crosstalk between the microbiome and epigenome: messages from bugs
abstract: Mammals exist in a complicated symbiotic relationship with their gut microbiome, which is postulated to have broad impacts on host health and disease. As omics based technologies have matured, the potential mechanisms by which the microbiome affects host physiology are being addressed. The gut microbiome, which provides environmental cues, can modify host cell responses to stimuli through alterations in the host epigenome and, ultimately, gene expression. Increasing evidence highlights microbial generation of bioactive compounds that impact the transcriptional machinery in host cells. Here, we review current understanding of the crosstalk between gut microbiota and the host epigenome, including DNA methylation, histone modification and non coding RNAs. These studies are providing insights into how the host responds to microbial signalling and are predicted to provide information for the application of precision medicine.