Proteomic Discovery of Stool Protein Biomarkers for Distinguishing Pediatric Inflammatory Bowel Disease Flares

Casavant, Ellen P.; Park, K.T.; Elias, Joshua E.

doi:10.1016/j.cgh.2019.08.052

Cited by 5 publications

(4 citation statements)

References 5 publications

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“…As was found in this study, Casavant et al identified proteins involved in neutrophil degranulation (S100A8, S100A9, MPO, ELANE) and plasma proteins (HBA1, HBB, and HP). Similar neutrophilic and plasma proteins were previously reported by others as well [12,13,67]. Interestingly, Basso et al were able to identify 193 human proteins in their study, of which only 161 showed any differential abundance in IBD stool, whereas in our study we identified 688 proteins, 422 of which showed statistically significant differential abundance in IBD stool.…”

Section: Discussionsupporting

confidence: 90%

“…In addition to food waste and bacterial products, stool is known to contain secreted human proteins and cellular debris, shed into the lumen as a result of immune cell activity and a damaged mucosal epithelial barrier of the gastrointestinal (GI) tract. Therefore, stool is a rich source of proteins that reflect overall gut health status and biologically relevant pathway activation information [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Profiling of the Human Fecal Proteome from IBD Patients with DIA-MS Enables Evaluation of Disease-Relevant Proteins

Harder,

Lekkerkerker,

Casavant

et al. 2024

Preprint

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Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for non-invasive biomarkers in IBD to detect mucosal inflammation to monitor changes in disease severity and guide treatment decisions. Fecal proteomics has the potential to allow frequent, non-invasive monitoring of biomarkers in stool of IBD patients, however the fecal proteome remains under explored. Here a data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts of IBD patients and healthy controls (HC) to identify non-invasive biomarkers reflective of disease activity. 688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to HC stool (absolute log2 fold change >1, p-value <0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping of the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome. Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential non-invasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Comprehensive Profiling of the Human Fecal Proteome from IBD Patients with DIA-MS Enables Evaluation of Disease-Relevant Proteins

Harder,

Lekkerkerker,

Casavant

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Some studies use data-dependent nanoLC–electrospray ionization MS/MS on a hybrid linear ion trap-FTICR-MS [ 166 ], while others have utilized tandem mass tag (TMT) labeling technique coupled with MS to increase the sensitivity and quantitation of differentially expressed proteins in tissue samples and microbial protein products expressed by a change in the gut environment [ 174 ]. The protein and peptide mass spectra obtained from LC–MS/MS is further analyzed and searched using UniProt, a human proteome sequence database [ 174 , 182 ].…”

Section: Methods Of Analysismentioning

confidence: 99%

The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling

Gangadoo

Rajapaksha

Cheeseman

et al. 2021

IJMS

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Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease.

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“…We and others have successfully applied proteomics methodologies to identify diagnostic biomarkers of IBD − and to evaluate the interplay between the microbiome and host in the pathogenesis of the disease. , Herein, we applied proteomics methods to better understand the disease process and evaluate the proteome changes associated with response to therapy in pediatric patients. By comparing the colon proteomes of individual patients before and after treatment, this study identified over 100 proteins to be differentially expressed between patients with mucosal healing (MH) and those with active disease (AD) following treatment.…”

Section: Introductionmentioning

confidence: 99%

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment

et al. 2021

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Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-nai ̈ve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the presence of noninflamed and/or inflamed regions in IBD patients, up to two biopsies were obtained from IBD patients as compared to a single noninflamed biopsy from non-IBD pediatric control patients. Additional biopsies were obtained and analyzed from 33 of the IBD patients after IBD-directed therapeutic intervention for comparison of pre-and post-treatment proteomes. SuperSILAC was utilized to perform quantitative analysis of homogenized tissues, which were processed by filter-aided sample preparation. Hierarchical clustering and principal component analyses revealed proteomic patterns that distinguished inflamed from noninflamed tissues independent of therapy. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of pre-and post-treatment proteomes from CD patients identified over 100 proteins that are significantly different between patients who responded and those who did not respond to therapy, including creatine kinase B and basigin.

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Proteomic Discovery of Stool Protein Biomarkers for Distinguishing Pediatric Inflammatory Bowel Disease Flares

Cited by 5 publications

References 5 publications

Comprehensive Profiling of the Human Fecal Proteome from IBD Patients with DIA-MS Enables Evaluation of Disease-Relevant Proteins

Comprehensive Profiling of the Human Fecal Proteome from IBD Patients with DIA-MS Enables Evaluation of Disease-Relevant Proteins

The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment

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