Dataset Information

Identifying fecal host biomarkers for the presence and severity of Clostridioides difficile infection using top-down proteomics

ABSTRACT: Clostridioides difficile is a major cause of healthcare-associated diarrhea in adult patients. Laboratory diagnosis of C. difficile infection (CDI) is challenging as there is no single test combining high sensitivity and specificity, rapid turnaround time and cost efficiency. They also offer no or little correlation with the clinical outcome. Recently, host-based methods have shown satisfactory performance for the diagnosis of infectious diseases. The aim of this study was to discover CDI-specific host biomarkers that correlate with disease stage and severity.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Feces

DISEASE(S): Clostridium Difficile Colitis

SUBMITTER: Momar Ndao

LAB HEAD: Momar Ndao

PROVIDER: PXD020117 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CD-neg-01_RC1_01_2144.mzXML	Mzxml
	CD-neg-01_RC1_01_2144_DeconvolutedPeaks.csv	Csv
	CD-neg-03_RC3_01_2149.mzXML	Mzxml
	CD-neg-03_RC3_01_2149_DeconvolutedPeaks.csv	Csv
	CD-neg-04_RC4_01_2151.mzXML	Mzxml

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Publications

Fecal host biomarkers predicting severity of Clostridioides difficile infection.

Golizeh Makan M Winter Kaitlin K Roussel Lucie L Landekic Marija M Langelier Mélanie M Loo Vivian G VG Ndao Momar M Vinh Donald C DC

JCI insight 20210111 1

Clostridioides difficile is a major cause of health care-associated diarrhea. Severity ranges from mild to life-threatening, but this variability remains poorly understood. Microbiologic diagnosis of C. difficile infection (CDI) is straightforward but offers little insight into the patient's prognosis or into pathophysiologic determinants of clinical trajectory. The aim of this study was to discover host-derived, CDI-specific fecal biomarkers involved in disease severity. Subjects without and wi ...[more]

PMID: 33232301

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Project description:A major risk factor for Clostridioides difficile infection (CDI) is the perturbation of the gut microbiota by antibiotic administration, and antibiotic therapy, the standard treatment option for CDI, exacerbates the imbalance of the gut microbiota, leading to a very high recurrent CDI (rCDI) incidence rate. Therefore, CDI treatment based on live biotherapeutic products (LBPs) has recently emerged for long-term CDI management and preventive treatment However, there is limited research and understanding of how these LBPs improve CDI symptoms, which raises the need to elucidate the therapeutic mechanisms of LBPs. To fill this knowledge gap, here, we holistically analyzed and investigated the mechanisms involved in the inhibitory effect of probiotics on C. difficile at the molecular level through a multiomics approach on screened strain from probiotics that inhibit C. difficile growth. First, Bifidobacterium species were co-cultured with C. difficile, and B. longum was screened based on its ability to inhibit the growth of C. difficile. Then, the antimicrobial activity of B. longum against C. difficile was confirmed by spot-on-lawn assay and organic acid quantification. Next, we performed proteomic and metabolomic analysis on C. difficile co-cultured with B. longum, and observed physiological changes associated with the inhibition of C. difficile growth and toxin production. It was found that lactate produced by B. longum up-regulated the lactate dehydrogenase complex of C. difficile, leading to a decrease in intracellular ATP synthesis and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Furthermore, proteinaceous stress induced by B. longum was also identified through the up-regulation of ribosomal proteins, molecular chaperones, and chaperonins, and the down-regulation of translation-related proteins. Finally, we found that B. longum suppressed butyrate metabolism and toxin production by producing and replenishing proline consumed by C. difficile. Therefore, this study will not only expand our understanding of the mechanisms of probiotics' inhibition of C. difficile, but also contribute to the development of LBPs based on molecular mechanisms for treating CDI.