Cytometric fingerprints of gut microbiota predict Crohn's disease state.
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ABSTRACT:
SUBMITTER: Rubbens P
PROVIDER: S-EPMC7852657 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD has been linked to specific bacteria, but reported associations vary widely across studies. This inconsistency may result from heterogeneous associations across individual patients, resulting in no apparent or only weak relationships with the means of bacterial abundances. We investigated the relationship between bacterial relative abundances and disease activity in a longitudinal cohort of CD patients (n = 57) and healthy controls (n = 15). We applied quantile regression, a statistical technique that allows investigation of possible relationships outside the mean response. We found several significant and mostly negative associations with CD, especially in lower quantiles of relative abundance on family or genus level. Associations found by quantile regression deviated from the mean response in relative abundances of Coriobacteriaceae, Pasteurellaceae, Peptostreptococcaceae, Prevotellaceae, and Ruminococcaceae. For the family Streptococcaceae we found a significant elevation in relative abundance for patients experiencing an exacerbation relative to those who remained without self-reported symptoms or measurable inflammation. Our analysis suggests that specific bacterial families are related to CD and exacerbation, but associations vary between patients due to heterogeneity in disease course, medication history, therapy response, gut microbiota composition and historical contingency. Our study underscores that microbial diversity is reduced in the gut of CD patients, but suggests that the process of diversity loss is rather irregular with respect to specific taxonomic groups. This novel insight may advance our ecological understanding of this complex disease.
| S-EPMC10730216 | biostudies-literature
Project description:The inflammatory intestinal disorder Crohn's disease (CD) has become a health challenge worldwide. The gut microbiota closely interacts with the host immune system, but its functional impact in CD is unclear. Except for studies on a small number of CD patients, analyses of the gut microbiota in CD have used 16S rDNA amplicon sequencing. Here we employed metagenomic shotgun sequencing to provide a detailed characterization of the compositional and functional features of the CD microbiota, comprising also unannotated bacteria, and investigated its modulation by exclusive enteral nutrition. Based on signature taxa, CD microbiotas clustered into 2 distinct metacommunities, indicating individual variability in CD microbiome structure. Metacommunity-specific functional shifts in CD showed enrichment in producers of the pro-inflammatory hexa-acylated lipopolysaccharide variant and a reduction in the potential to synthesize short-chain fatty acids. Disruption of ecological networks was evident in CD, coupled with reduction in growth rates of many bacterial species. Short-term exclusive enteral nutrition elicited limited impact on the overall composition of the CD microbiota, although functional changes occurred following treatment. The microbiotas in CD patients can be stratified into 2 distinct metacommunities, with the most severely perturbed metacommunity exhibiting functional potentials that deviate markedly from that of the healthy individuals, with possible implication in relation to CD pathogenesis.
| S-EPMC5624284 | biostudies-literature
Project description:BackgroundThe dysbiosis of the gut microbiome is evident in Crohn's disease (CD) compared with healthy controls (HC), although the alterations from active CD to remission after treatment are unclear.AimTo characterize the mucosa-associated gut microbiota in patients with CD before and after the induction therapy.MethodsThe basic information was collected from the subjects and the CD activity index (CDAI) was calculated in patients. A 16S rRNA sequencing approach was applied to determine the structures of microbial communities in mucosal samples including the terminal ileal, ascending colon, descending colon and rectum. The composition and function of mucosa-associated gut microbiota were compared between samples from the same cohort of patients before and after treatment. Differential taxa were identified to calculate the microbial dysbiosis index (MDI) and the correlation between MDI and CDAI was analyzed using Pearson correlation test. Predictive functional profiling of microbial communities was obtained with PICRUSt.ResultsThere were no significant differences in microbial richness among the four anatomical sites in individuals. Compared to active disease, the alpha diversity of CD in remission was increased towards the level of HC compared to the active stage. The principal coordinate analysis revealed that samples of active CD were clearly separated from those in remission, which clustered close to HC. Sixty-five genera were identified as differentially abundant between active and quiescent CD, with a loss of Fusobacterium and a gain of potential beneficial bacteria including Lactobacillus, Akkermansia, Roseburia, Ruminococcus and Lachnospira after the induction of remission. The combination of these taxa into a MDI showed a positive correlation with clinical disease severity and a negative correlation with species richness. The increased capacity for the inferred pathways including Lipopolysaccharide biosynthesis and Lipopolysaccharide biosynthesis proteins in patients before treatment negatively correlated with the abundance of Roseburia, Ruminococcus and Lachnospira.ConclusionThe dysbiosis of mucosa-associated microbiota was associated with the disease phenotype and may become a potential diagnostic tool for the recurrence of disease.
| S-EPMC6526154 | biostudies-literature
Project description:Background: Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood. Methods: To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. In-silico profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways. Results: Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways. Conclusions: In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.
| S-EPMC7729129 | biostudies-literature
Project description:BackgroundThe gut microbiome is altered in Crohn's disease. Although individual taxa have been correlated with post-operative clinical course, global trends in microbial diversity have not been described in this context.MethodsWe collected mucosal biopsies from the terminal ileum and ascending colon during surgery and post-operative colonoscopy in 6 Crohn's patients undergoing ileocolic resection (and 40 additional Crohn's and healthy control patients undergoing either surgery or colonoscopy). Using next-generation sequencing technology, we profiled the gut microbiota in order to identify changes associated with remission or recurrence of inflammation.ResultsWe performed 16S ribosomal profiling using 101 base-pair single-end sequencing on the Illumina GAIIx platform with deep coverage, at an average depth of 1.3 million high quality reads per sample. At the time of surgery, Crohn's patients who would remain in remission were more similar to controls and more species-rich than Crohn's patients with subsequent recurrence. Patients remaining in remission also exhibited greater stability of the microbiota through time.ConclusionsThese observations permitted an association of gut microbial profiles with probability of recurrence in this limited single-center study. These results suggest that profiling the gut microbiota may be useful in guiding treatment of Crohn's patients undergoing surgery.
| S-EPMC3848607 | biostudies-literature
Project description:BackgroundEmerging evidence suggests that gut microbiota plays a predominant role in Crohn's disease (CD). However, the microbiome alterations in the early stage of CD patients still remain unclear. The present study aimed to identify dysbacteriosis in patients with early CD and explore specific gut bacteria related to the progression of CD.MethodsThis study was nested within a longitudinal prospective Chinese CD cohort, and it included 18 early CD patients, 22 advanced CD patients and 30 healthy controls. The microbiota communities were investigated using high-throughput Illumina HiSeq sequencing targeting the V3-V4 region of 16S ribosomal DNA (rDNA) gene. The relationship between the gut microbiota and clinical characteristics of CD was analyzed.ResultsDifferential microbiota compositions were observed in CD samples (including early and advanced CD samples) and healthy controls samples. Notably, Lachnospiracea_incertae_sedis and Parabacteroides were enriched in the early CD patients, Escherichia/Shigella, Enterococcus and Proteus were enriched in the advanced CD patients, and Roseburia, Gemmiger, Coprococcus, Ruminococcus 2, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, Clostridium IV were enriched in the healthy controls [LDA score (log10) > 2]. Furthermore, Kruskal-Wallis Rank sum test results showed that Blautia, Clostridium IV, Coprococcus, Dorea, Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase compared with healthy controls (P < 0.05). The PICRUSt analysis identified 16 remarkably different metabolic pathways [LDA score (log10) > 2]. Some genera were significantly correlated with various clinical parameters, such as fecal calprotectin, erythrocyte sedimentation rate, C-reactive protein, gland reduce, goblet cells decreased, clinical symptoms (P < 0.05).ConclusionsDysbacteriosis occurs in the early stage of CD and is associated with the progression of CD. This data provides a foundation that furthers the understanding of the role of gut microbiota in CD's pathogenesis.
| S-EPMC9753350 | biostudies-literature
Project description:BackgroundPredicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.ObjectivesThis study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD.MethodsIn children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR).ResultsOf 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN.ConclusionsWe identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
| S-EPMC11007740 | biostudies-literature
Project description:Intestinal tuberculosis (ITB) and Crohn's disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.
| S-EPMC8290844 | biostudies-literature
Project description:ObjectivesPreventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial.DesignMicrobiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis.ResultsICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/β Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence.ConclusionsICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.
| S-EPMC4893116 | biostudies-literature
Project description:Previous studies have demonstrated that patients with Crohn's disease (CD) in remission do not exhibit an improvement in gut microbiota composition, which might trigger relapses. The present study investigated the dysbiosis and mucins production in CD patients during remission. We performed an analytical cross-sectional single center study, which recruited 18 CD patients and 18 healthy controls (CG) residing in the same home, meaning that all of the participants experienced the same environmental factors, with similar hygiene status, diet, pollution and other common lifestyle characteristics that may influence the composition of the gut microbiota. When compared to healthy controls, the CD patients exhibited lower microbial α-diversity (p = 0.047), a greater abundance of the Proteobacteria phylum (p = 0.037) and a reduction in the Deltaproteobacteria class (p = 0.0006). There was also a reduction in the Akkermansia (p = 0.002) and Oscillospira (p = 0.024) genera and in the proportion of the yeast Saccharomyces cerevisiae (p = 0.01). Additionally, CD patients in remission presented increased neutral (p = 0.001) and acid mucin (p = 0.002) concentrations. The reductions in the proportions of Oscollospira and Akkermansia genera, sulfate-reducing bacteria and Saccharomyces cerevisiae, observed in the CD group, may account for the increased mucins production observed in these patients.
| S-EPMC6744406 | biostudies-literature