Identification of the intestinal microbiome of gallstone patients by metagenomic sequencing
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PROVIDER: PRJEB61425 | ENA |
REPOSITORIES: ENA
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Project description:Intestinal microbial community of gallstone patients
| PRJEB61273 | ENA
Project description:Intestinal microbial community of gallstone patients
| PRJEB61402 | ENA
Project description:Background and aims: Gene mutations or variants leading to insufficient reactive oxygen species (ROS) production have been associated with inflammatory bowel disease (IBD). In particular, 40-50% of patients with chronic granulomatous disease have IBD (CGD-IBD). CGD is caused by inherited defects in any one of the 5 subunits forming the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived ROS production. While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection in this immune compromised population. Understanding the impact of NOX2 defects on the composition and function of the intestinal microbiota may lead to the identification of treatments for CGD-IBD. Methods: We evaluated GI symptom and quality of life scores, and clinical biomarkers of local (i.e. fecal occult blood and calprotectin) and systemic (i.e. CBC, CRP, ESR, and albumin) inflammation in a cohort of 79 patients with CGD, 8 mutation carriers and 17 healthy controls followed at the National Institutes of Health (NIH). We profiled the intestinal microbiome by 16S rRNA (V4 region) sequencing and the stool metabolome by mass spectrometry in all fecal samples, and further validated our findings by profiling the stool microbiome in a second cohort of 36 patients with CGD recruited from 11 centers across North-America through the Primary Immune Deficiency Treatment Consortium (PIDTC). Predictive functional profiling of the microbial communities based on 16S rRNA sequencing was also performed. Results: After controlling for significant variables, we show decreased alpha diversity and identified distinct intestinal microbiome and metabolomic profiles in patients with CGD compared to healthy individuals. In particular, we observed enrichment for Erysipelatoclostridium spp., Sellimonas spp. and Lachnoclostridium spp. in stool samples from patients with CGD. Despite differences in alpha and beta diversity in samples from the NIH compared to the PIDTC cohort, there were several bacterial taxa that correlated significantly between both cohorts. We further demonstrate that patients with active IBD and/or a history of IBD have a distinct microbiome and metabolomic profile compared to patients without CGD-IBD and identified bacterial taxa to be evaluated as potential markers of disease severity, as well as targets for future therapeutic interventions. Conclusions: Intestinal microbiome and metabolomic signatures distinguished patients with CGD and CGD-IBD and identified microbial and metabolomic candidates to be further evaluated as potential targets to improve the management of patients with CGD-IBD.
2023-12-04 | GSE220260 | GEO
Project description:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.
2023-08-30 | GSE181270 | GEO
Project description:Gallstone disease (GD) is one of the most common gastrointestinal diseases worldwide. Nowadays, intestinal microbiota are thought to play important roles in the formation of gallstones. In our study, human fecal samples were extracted for metagenomic next-generation sequencing (mNGS) on the Illumina HiSeq platform, followed by bioinformatics analyses. Our results showed that there was a particular intestinal micro-ecosystem in GD patients. In contrast to healthy people, the sequences of Bacteroidetes, Bacteroides and Thetaiotaomicron were obviously more abundant in GD patients at phylum, genus and species levels, respectively. On the other hand, the glycan metabolism and drug resistance, especially for the β-lactams, were the most profound functions of gut microbes in GD patients compared to those in normal subjects. Furthermore, a correlation analysis drew out that there existed a significant relationship between the serum levels of biochemical indicators and abundances of intestinal microbes in GD patients. Our results illuminate both the composition and functions of intestinal microbiota in GD patients. All in all, our study can broaden the insight into the potential mechanism of how gut microbes affect the progression of gallstones to some extent, which may provide potential targets for the prevention, diagnosis or treatment of GD.
| S-EPMC10453932 | biostudies-literature
Project description:Epigenome-wide methylation levels were measured in patients from Chiel with gallstone disease, gallbladder dyplasia or gallbladder cancer using Illumina Infinium methylation arrays.
2020-12-12 | E-MTAB-9868 | biostudies-arrayexpress
Project description:Following a large-scale genome-wide association study of gallstone disease, we performed RNA sequencing from tissues of four human gallbladders (3 healthy controls and 1 case with chronic gallstones) and one liver sample from the gallstone case. We aimed to determine the expression patterns of gallstone disease-associated genes in gallbladder and liver, two organs of interest in disease etiology.
2016-04-21 | GSE66430 | GEO
Project description:A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. 6 samples, 2 biological replicates for each 3 conditions.
2015-12-16 | E-GEOD-65790 | biostudies-arrayexpress
Project description:To investigate the role of gut microbiota on the formation of cholesterol gallstone in mice.
2019-12-31 | E-MTAB-8550 | biostudies-arrayexpress