Fecal host biomarkers predicting severity of Clostridioides difficile infection

Golizeh, Makan; Winter, Kaitlin; Roussel, Lucie; Landekic, Marija; Langelier, Mélanie; Loo, Vivian G.; Ndao, Momar; Vinh, Donald C.

doi:10.1172/jci.insight.142976

Cited by 4 publications

(6 citation statements)

References 51 publications

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“…Essentially, proteins are separated by liquid chromatography and detected by mass spectrometry. Interesting candidates are identified following rigorous statistical analysis of MS/MS data for further structural and biological information . Although top-down proteomics was more of a fringe method with limited application to clinical samples, top-down approaches are now gaining more and more popularity in forensics and doping control. − The point of this Perspective is thus to highlight how top-down proteomics can contribute to toxicology research in public health and to the battle against sports doping.…”

Section: Lc-ms/(ms)-based Proteomicsmentioning

confidence: 99%

Using Proteins As Markers for Anabolic Steroid Abuse: A New Perspective in Doping Control?

Sansoucy

Naud

2023

Chem. Res. Toxicol.

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Drug toxicity is a major concern and has motivated numerous studies to elucidate specific adverse mechanisms, with acetaminophen being the favorite candidate in toxicology studies. Conversely, androgenic anabolic steroids (AASs) also represent a severe public health issue in sports for elite and non-elite athletes. Supraphysiological dosages of AASs are associated with various adverse effects, from cardiovascular to neurological repercussions including liver dysfunction. Yet, few studies have addressed the toxicity of anabolic steroids, and a significant amount of work will be needed to elucidate and understand steroid toxicity properly. This Perspective suggests ideas on how proteomics and liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) can contribute to (1) pinpoint serum proteins affected by substantial doses of anabolic steroids that would represent interesting novel candidates for routine testing and (2) provide additional knowledge on androgenic anabolic steroid toxicity to help raise awareness on the harmful effects. ■ CONTENTSIntroduction 1168 LC-MS/(MS)-

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Section: Lc-ms/(ms)-based Proteomicsmentioning

confidence: 99%

Using Proteins As Markers for Anabolic Steroid Abuse: A New Perspective in Doping Control?

Sansoucy

Naud

2023

Chem. Res. Toxicol.

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“…The relative abundance of alpha-1-antitrypsin was significantly higher in non-severe than severe patients ( p = .028), identifying it as a putative biomarker of severity. 82 …”

Section: Microbiologic Factors Associated With CDI Outcomesmentioning

confidence: 99%

“…The relative abundance of alpha-1-antitrypsin was significantly higher in non-severe than severe patients (p = .028), identifying it as a putative biomarker of severity. 82 Another strategy to profile the association between immune response and CDI severity is to measure systemic biomarkers in circulation. One of the early studies (78 cases; 8 of them met CDC severity criteria) found that severe patients had significantly elevated levels of IL-8 [odds ratio (OR) = 5.92; 95% CI = 1.13-31.1] and IL-6 (OR = 3.12; 95% CI = 1.05-9.28).…”

Section: Therapeutic Advances In Gastroenterology 14mentioning

confidence: 99%

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

Ressler

Wang

Rao

2021

Therap Adv Gastroenterol

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In the United States, Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infection, affecting nearly half a million people and resulting in more than 20,000 in-hospital deaths every year. It is therefore imperative to better characterize the intricate interplay between C. difficile microbial factors, host immunologic signatures, and clinical features that are associated with adverse outcomes of severe CDI. In this narrative review, we discuss the implications of C. difficile genetics and virulence factors in the molecular epidemiology of CDI, and the utility of early biomarkers in predicting the clinical trajectory of patients at risk of developing severe CDI. Furthermore, we identify associations between host immune factors and CDI outcomes in both animal models and human studies. Next, we highlight clinical factors including renal dysfunction, aging, blood biomarkers, level of care, and chronic illnesses that can affect severe CDI diagnosis and outcome. Finally, we present our perspectives on two specific treatments pertinent to patient outcomes: metronidazole administration and surgery. Together, this review explores the various venues of CDI research and highlights the importance of integrating microbial, host, and clinical data to help clinicians make optimal treatment decisions based on accurate prediction of disease progression.

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“…Using this method, a recent paper by Golizeh identified fecal host proteins that may be useful in differentiating C. difficile infection from other causes of diarrhea and seem to correlate with clinical severity [62]. Alpha-2 macroglobulin and matrix metalloproteinase-7 are produced by the intestinal mucosal epithelium and levels may correlate with disease severity [62]. Protection from inflammation is associated with the presence of alpha-1-antitrypsin and levels of this serine protease inhibitor negatively correlate with disease severity [62].…”

Section: Using Biomarkersmentioning

confidence: 99%

“…Alpha-2 macroglobulin and matrix metalloproteinase-7 are produced by the intestinal mucosal epithelium and levels may correlate with disease severity [62]. Protection from inflammation is associated with the presence of alpha-1-antitrypsin and levels of this serine protease inhibitor negatively correlate with disease severity [62].…”

Section: Using Biomarkersmentioning

confidence: 99%

The future of Clostridioides difficile diagnostics

Mizusawa

Carroll

2021

Current Opinion in Infectious Diseases

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Purpose of review Although the epidemiology of Clostridioides difficile has changed, this organism continues to cause significant morbidity and mortality. This review addresses current and future approaches to the diagnosis of C. difficile disease. Recent findings Over the last several years, large prospective studies have confirmed that there is no single optimal test for the diagnosis of C. difficile disease. The pendulum has swung from a focus on rapid molecular diagnosis during the years of the ribotype 027 epidemic, to a call for use of algorithmic approaches that include a test for toxin detection. In addition, diagnostic stewardship has been shown to improve test utilization, especially with molecular methods. Advances in testing include development of ultrasensitive toxin tests and an expansion of biomarkers that may be more C. difficile specific. Microbiome research may be leveraged to inform novel diagnostic approaches based on measurements of volatile and nonvolatile organic compounds in stool. Summary As rates of C. difficile infection decline, emphasis is now on improving test utilization and a quest for improved diagnostic approaches. These approaches may involve implementation of technologies that improve toxin testing, predict patients likely to have disease and/or a severe outcome, and harnessing research on changes in the microbiome to advance metabolomics.

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Fecal host biomarkers predicting severity of Clostridioides difficile infection

Cited by 4 publications

References 51 publications

Using Proteins As Markers for Anabolic Steroid Abuse: A New Perspective in Doping Control?

Using Proteins As Markers for Anabolic Steroid Abuse: A New Perspective in Doping Control?

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

The future of Clostridioides difficile diagnostics

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