The relationship between the gut microbiome and host gene expression: a review.
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ABSTRACT:
SUBMITTER: Nichols RG
PROVIDER: S-EPMC7680557 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have led to markedly increased longevity of patients with cystic fibrosis, but new complications have emerged, such as early onset of colorectal cancer. Although the pathogenesis of colorectal cancer in cystic fibrosis remains unclear, altered host-microbe interactions might play a critical role. To investigate this, we characterized changes in the microbiome and host gene expression in the colonic mucosa of cystic fibrosis patients relative to healthy controls, and identified host gene-microbiome interactions in the colon of cystic fibrosis patients.MethodsWe performed RNA-seq on colonic mucosa samples from cystic fibrosis patients and healthy controls to determine differentially expressed host genes. We also performed 16S rRNA sequencing to characterize the colonic mucosal microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression.ResultsWe find that 1543 genes, including CFTR, show differential expression in the colon of cystic fibrosis patients compared to healthy controls. These genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of colorectal cancer, tumor suppression, p53, and mTOR signaling pathways. In addition, patients with cystic fibrosis show decreased gut microbial diversity, decreased abundance of butyrate producing bacteria, such as Ruminococcaceae and Butyricimonas, and increased abundance of other taxa, such as Actinobacteria and Clostridium. An integrative analysis identified colorectal cancer-related genes, including LCN2 and DUOX2, for which gene expression is correlated with the abundance of colorectal cancer-associated bacteria, such as Ruminococcaceae and Veillonella.ConclusionsIn addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis.
| S-EPMC6988342 | biostudies-literature
Project description:Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.
| S-EPMC8490573 | biostudies-literature
Project description:The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.
| S-EPMC6776654 | biostudies-literature
Project description:Ageing is associated with changes in biological processes, including reductions in cognitive functions and gut microbiome diversity. However, not much is known about the relationship between cognition and the microbiome with increasing age. Therefore, we examined the relationship between the gut microbiome and cognition in 69 healthy participants aged 60-75 years. The gut microbiome was analysed with the 16S rRNA sequencing method. The cognitive assessment included the Cognitive Drug Research computerised assessment battery, which produced five cognitive factors corresponding to 'Quality of Episodic Secondary Memory', 'Quality of Working Memory', 'Continuity of Attention, 'Speed of Memory' and 'Power of Concentration'. Multiple linear regression showed that the bacterial family Carnobacteriaceae explained 9% of the variance in predicting Quality of Episodic Secondary Memory. Alcaligenaceae and Clostridiaceae explained 15% of the variance in predicting Quality of Working Memory; Bacteroidaceae, Barnesiellaceae, Rikenellaceae and Gemellaceae explained 11% of the variance in Power of Concentration. The present study provides specific evidence of a relationship between specific families of bacteria and different domains of cognition.
| S-EPMC8746300 | biostudies-literature
Project description:Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM.In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the 'VFM diet score' in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (?1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence.Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (-0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (-0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6).We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.
| S-EPMC5504448 | biostudies-other
Project description:ObjectiveThe prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of cancer therapy, especially immunotherapy. There is limited evidence to date on the influence of microbes on chemotherapeutic response.DesignIn total, 130 patients with advanced or metastatic esophageal (n=40), gastric (n=46), and colorectal cancer (n=44) were enrolled. We included 147 healthy people as controls and used 16S rRNA sequencing to analyze the fecal microbiota.ResultsSignificant differences in the abundance of fecal microbiota between patients with gastrointestinal cancer and controls were identified. The abundance of Bacteroides fragilis, Escherichia coli, Akkermansia muciniphila, Clostridium hathewayi, and Alistipes finegoldii were significantly increased in the patient group. Faecalibacterium prausnitzii, Roseburia faecis, Clostridium clostridioforme, Blautia producta, Bifidobacterium adolescent, and Butyricicoccus pullicaecorum taxa were significantly more abundant in the controls. The amount of R. faecis in non-responders (NR) was more likely to decrease significantly after chemotherapy, while the amount mostly increased in responders (R) (P=0.040). The optimal abundance variation of R. faecis may be a predictor for distinguishing patients with PD from those with non-PD in all patients with gastrointestinal cancer, with a sensitivity of 75.0% and a specificity of 93.9%.ConclusionThe gut microbiome of patients with esophageal cancer, gastric cancer, and colorectal cancer differs from those of healthy people. The abundance alteration of R. faecis in patients with GI cancer might be a predictor of chemotherapy efficacy.
| S-EPMC8733568 | biostudies-literature
Project description:BACKGROUND:The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking. RESULTS:We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1?M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation. CONCLUSIONS:Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC.
| S-EPMC7178946 | biostudies-literature
Project description:The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children. Additional correlations between responses to TLR2 and bacterial populations were specific to individual geographic cohorts. As a proof of concept, we gavaged germfree mice with human donor stools and found murine splenocyte responses to TLR stimulation were consistent with responses of the corresponding human donor populations. This study identified differences in immune responses correlating to gut microbiomes across biogeographically diverse settings and evaluated biological plausibility using a mouse model. This insight paves the way to guide optimization of population-specific interventions aimed to improve child health outcomes.IMPORTANCE Both the gut microbiome and innate immunity are known to differ across biogeographically diverse human populations. The gut microbiome has been shown to directly influence systemic immunity in animal models. With this, modulation of the gut microbiome represents an attractive avenue to improve child health outcomes associated with altered immunity using population-specific approaches. However, there are very scarce data available to determine which members of the gut microbiome are associated with specific immune responses and how these differ around the world, creating a substantial barrier to rationally designing such interventions. This study addressed this knowledge gap by identifying relationships between distinct bacterial taxa and cytokine responses to specific microbial agonists across highly diverse settings. Furthermore, we provide evidence that immunomodulatory effects of region-specific stool microbiomes can be partially recapitulated in germfree mice. This is an important contribution toward improving global child health by targeting the gut microbiome.
| S-EPMC7845628 | biostudies-literature
Project description:Primates have evolved a variety of feeding habits and intestinal physiological structure. Gut microbiome act as metabolic organs in many biological processes and play a vital role in adaptation to dietary niches. Gut microbiome also convert primary bile acids (BAs) to secondary. BAs profile and gut microbiome are together influenced by diets and play a significant role in nutrient absorption. The regulation between gut microbiome and BAs metabolism is bidirectional although the relationship in primates consuming diverse diets is still unclear. Here, we investigated gut microbiome structures, fecal BAs profile, and their relationship in primates preferring three distinct diets. We found that gut microbiome communities are well differentiated among dietary groups. Folivorous primates had higher Firmicutes abundance and lower Prevotella to Bacaeroides ratios, possibly related to fiber consumption. Frugivorous primates are colonized predominantly by Prevotella and Bacteroides, pointing to an increased adaptation to high-sugar and simple carbohydrate diets. Likewise, BA profiles differ according to diet in a manner predictable from the known effects of BAs on metabolism. Folivorous primates have high conjugated bile acid levels and low unconjugated to conjugated BA ratios, consistent with their fiber-rich leaf-eating diet. Much of the differentiation in secondary and unconjugated BAs is associated with microbiome composition shifts and individual bile acid concentrations are correlated with the abundance of distinct bacterial taxonomic groups. Omnivores have higher concentrations of secondary BAs, mainly lithocholic acid (LCA). These levels are significantly positively correlated with the presence of Clostrida species, showing that the digestion requirements of omnivores are different from plant-eating primates. In conclusion, gut microbiome and BAs can respond to changes in diet and are associated with nutrient component consumption in each diet primate group. Our study is the first to demonstrate BA profile differentiation among primates preferring diverse diets. BAs thus appear to work with gut microbiome to help primates adapt to their diet.
| S-EPMC9130754 | biostudies-literature
Project description:Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal relationship. To reveal the causal relationship between gut microbiota and cardiovascular protein levels in plasma, we estimated their causal effects using two-sample Mendelian randomization (MR) analysis. Sensitivity analysis was also performed to assess the robustness of our results. Genome-wide association study (GWAS) of microbiomes in the MiBioGen study included 211 bacterial taxa (18,473 individuals), and GWAS of 90 cardiovascular proteins included 30,931 individuals. There were 196 bacterial taxa from five levels available for analysis. The following 14 causal relationships were identified: phylum Euryarchaeota and carbohydrate antigen 125 (β = 0.289), order Bacillales and CSF-1 (β = -0.211), genus Dorea and HSP-27 (β = 0.465), phylum Actinobacteria and IL-8 (β = 0.274), order Enterobacteriales and KIM-1 (β = -0.499), class Actinobacteria, genus Bifidobacterium, phylum Actinobacteria and LEP (β = -0.219, β = -0.201, and β = -0.221), genus Methanobrevibacter and NT-proBNP (β = 0.371), family Peptostreptococcaceae and SRC (β = 0.191), order Verrucomicrobiales, phylum Verrucomicrobia and TNF-R2 (β = 0.251 and β = 0.233), family Veillonellaceae and t-PA (β = 0.271), and class Erysipelotrichia and VEGF-D (β = 0.390). Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. The results of the reverse MR analysis showed no reverse causality for any of the 13 gut microbes and 11 cardiovascular proteins. Mendelian randomization estimates provide strong evidence for a causal effect of gut microbiota-mediated alterations on cardiovascular protein expression.
| S-EPMC9760811 | biostudies-literature