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The Gut Microbiome and Butyrate Differentiate Clostridioides difficile Colonization and Infection in Children

M. Nicholson, Siyuan Ma, B. Strickland, Mia Cecala, Lisa S. Zhang, Seth Andrew Reasoner, Emma R. Guiberson, Matthew J. Munneke et al.

bioRxiv, 2025

55 participants · 1 citation

Abstract

Background and Aims Symptomatic Clostridioides difficile infection (CDI) can cause significant morbidity and mortality. Conversely, patients can be colonized with toxigenic C. difficile in the absence of symptoms, termed asymptomatic colonization. We previously demonstrated that the presence and function of C. difficile toxins do not differentiate between asymptomatic colonization and CDI in children, suggesting the influence of other factors. This study aimed to interrogate the intestinal microbiome and butyrate in stool samples from children with CDI and asymptomatic colonization. Methods Design: Case-control study Setting: Tertiary care children’s hospital Participants and measures: Asymptomatic children had stool tested for C. difficile by nucleic-acid amplification-based testing (NAAT) and were considered colonized if positive (N=50). Residual stool was also obtained from symptomatic children who tested positive for C. difficile by NAAT (N=55). The microbiome was assessed via 16S rRNA sequencing and butyrate via liquid chromatography-mass spectrometry. Results Compared to clinical co-variates and comorbidities, C. difficile symptom status (i.e., asymptomatic colonization versus symptomatic CDI) demonstrated the strongest differential abundance association on gut microbes. Symptomatic CDI was associated with increased abundance of Escherichia/Shigella (Benjamini-Hochberg adjusted q=3.94×10−5), Haemophilus (q=0.022), and Gemella (q=0.085), and depleted abundance of gut…

How strong is the evidence?

Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 55 participants or records.

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