scholarly journals Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xu Zhang ◽  
Zhibin Ning ◽  
Janice Mayne ◽  
Yidai Yang ◽  
Shelley A. Deeke ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Lysine Acetylation ◽  
Protein Lysine Acetylation

scholarly journals Deep characterization of the protein lysine acetylation in human gut microbiome and its alterations in patients with Crohn’s disease

2019 ◽  
Author(s):  
Xu Zhang ◽  
Zhibin Ning ◽  
Janice Mayne ◽  
Shelley A. Deeke ◽  
Krystal Walker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Human Microbiome ◽  
Host Protein ◽  
Lysine Acetylation ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Human Proteins ◽  
Protein Lysine Acetylation

AbstractMetagenomic and metaproteomic approaches have been used to study the composition and functions of the microbiota. However, no studies have examined post-translational modifications (PTM) on human microbiome proteins at the metaproteome level, and it remains unknown whether the microbial PTM is altered or not in patient microbiome. Herein we used anti-acetyl-lysine (Kac) antibody enrichment strategy and mass spectrometry to characterize the protein lysine acetylation in human microbiome, which successfully identified 35,200 Kac peptides corresponding to 31,821 Kac sites from the microbial or host proteins in human gut microbiome samples. The gut microbial proteins exhibited Kac motifs that were distinct from those of human proteins. Functional analysis showed that microbial Kac proteins were significantly enriched in energy production and abundant in enzymes related to transferases and oxidoreductases. Applying to the analysis of pediatric Crohn’s disease (CD) patient microbiome identified 52 host and 136 microbial protein Kac sites that were differentially abundant in CD versus controls. Interestingly, most of the decreased Kac sites in CD were derived from Firmicutes and most of the increased sites were derived from Bacteroidetes. Forty-six out of the 52 differentially abundant human protein Kac sites were increased in CD patients, including those on calprotectin, lactotransferrin and immunoglobulins. Taken together, this study provides an efficient approach to study the lysine acetylation in microbiome and revealed taxon-specific alterations in the lysine acetylome as well as changes in host protein acetylation levels in intestinal samples during the on-set of disease in CD patients.

Sa595 DIETARY INFLAMMATORY POTENTIAL AND FOOD PATTERNS IN RELATION TO GUT MICROBIOME AMONG CHILDREN WITH CROHN'S DISEASE: A COMPARATIVE STUDY WITH HEALTHY CONTROLS

2021 ◽  
Vol 160 (6) ◽  
pp. S-566
Author(s):  
Jessica Breton ◽  
Vincent Tu ◽  
Ceylan Tanes ◽  
Maire A. Conrad ◽  
Kelly Kachelries ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Comparative Study ◽  
Gut Microbiome ◽  
Healthy Controls ◽  
Food Patterns

scholarly journals Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Jagadesan Sankarasubramanian ◽  
Rizwan Ahmad ◽  
Nagavardhini Avuthu ◽  
Amar B. Singh ◽  
Chittibabu Guda
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Meta Analysis ◽  
Metabolic Effects ◽  
Taxonomic Rank ◽  
Disease Specific

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.

scholarly journals Gut Microbiome in New-Onset Crohn's Disease

2014 ◽  
Vol 147 (4) ◽  
pp. 932-934 ◽  
Author(s):  
Lindsay J. Hall ◽  
John Walshaw ◽  
Alastair J.M. Watson
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
New Onset

scholarly journals A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition

2016 ◽  
Vol 151 (4) ◽  
pp. 724-732 ◽  
Author(s):  
Dalin Li ◽  
Jean-Paul Achkar ◽  
Talin Haritunians ◽  
Jonathan P. Jacobs ◽  
Ken Y. Hui ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Missense Variant ◽  
Human Gut ◽  
Microbiome Composition ◽  
Human Gut Microbiome

scholarly journals Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Grégoire Chevalier ◽  
Arnaud Laveissière ◽  
Guillaume Desachy ◽  
Nicolas Barnich ◽  
Adeline Sivignon ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Adhesion ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Promising Therapeutic Approach ◽  
Activity Dependent

Abstract Background An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn’s Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota. Results We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity. Conclusions We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence.

scholarly journals Anti-inflammatory Gut Microbial Pathways Are Decreased During Crohn’s Disease Exacerbations

2019 ◽  
Vol 13 (11) ◽  
pp. 1439-1449 ◽  
Author(s):  
Marjolein A Y Klaassen ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Jingyuan Fu ◽  
Cisca Wijmenga ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Inflammatory Disorder ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Anti Inflammatory ◽  
Clinical Records

Abstract Background and Aims Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity. Methods Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software. Results In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] <0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs]. Conclusions CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.

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