Analysis of Intestinal Mycobiota of Patients with Clostridioides difficile Infection among a Prospective Inpatient Cohort.

Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE

Original Publication: Washington, DC : ASM Press, 2013-

Clostridioides difficile* ; Clostridium Infections*/diagnosis ; Clostridium Infections*/microbiology; Diarrhea/microbiology ; Ecosystem ; Humans ; Inpatients ; Prospective Studies

Clostridioides difficile infection (CDI) is a burden to health care systems worldwide. Gut microbiota dysbiosis associated with CDI has been well accepted. However, contribution of fungal mycobiota to CDI has recently gained research interest. Here, we report the gut mycobiota composition of 149 uniquely well characterized participants from a prospective clinical cohort and evaluate the discriminating ability of gut mycobiota to classify CDI and non-CDI patients. Fecal samples were divided into two groups: (i) CDI (inpatients who had clinically significant diarrhea and positive nucleic acid amplification testing [NAAT] and received subsequent CDI therapy, n  = 58) and (ii) non-CDI, which can be further divided into three subgroups: (a) carrier (inpatients with positive stool NAAT but without diarrhea; n  = 28); (b) diarrhea (inpatients with negative stool NAAT; n  = 31); and (c) control (inpatients with negative stool NAAT and without diarrhea; n  = 32). Fecal mycobiota composition was analyzed by internal transcribed spacer 2 (ITS2) sequencing. In comparison to non-CDI patients, CDI patients tend to have gut mycobiota with lower biodiversity, weaker fungi correlations, and weaker correlations between fungi and host immune factors. Notably, 11 genera (Saccharomyces, Penicillium, Aspergillus, Cystobasidium, Cladosporium, and so on) were significantly enriched in non-CDI patients, and Pichia and Suhomyces were enriched in patients with CDI, while 1 two genera, Cystobasidium and Exophiala, had higher abundance in patients with diarrhea compared with CDI (linear discriminant analysis [LDA] > 3.0; P <  0.05). Ascomycota and Basidiomycota (or Candida and Saccharomyces) exhibited a strong negative correlation ( r ≤ -0.714 or r ≤ -0.387; P <  0.05), and the ratios of Ascomycota to Basidiomycota or genera Candida to Saccharomyces were dramatically higher in CDI patients than in non-CDI patients ( P <  0.05). A disease-specific pattern with much weaker fungal abundance correlations was observed in the CDI group compared to that in the non-CDI and diarrhea groups, suggesting that these correlations may contribute to the development of CDI. Our findings provided specific markers of stool fungi that distinguish CDI from all non-CDI hospitalized patients. This study's potential clinical utility for better CDI diagnosis warrants further investigation. IMPORTANCE Clostridioides difficile is an opportunistic bacterial pathogen that causes a serious and potentially life-threatening infection of the human gut. It remains an existing challenge to distinguish active infection of CDI from diarrhea with non-CDI causes. A few large prospective studies from recent years suggest that there is no single optimal test for the diagnosis of CDI. Previous research has concentrated on the relationship between bacteria and CDI, while the roles of fungi, as a significant proportion of the gut microbial ecosystem, remain understudied. In this study, we report a series of fungal markers that may add diagnostic values for the development of a more systematic approach to accurate CDI diagnosis. These results help open the door for better understanding of the relationship between host immune factors and the fungal community in the context of CDI pathogenesis.

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U19 AI095219 United States AI NIAID NIH HHS; U01 HL089856 United States HL NHLBI NIH HHS; RF1 AG067744 United States AG NIA NIH HHS; R01 AI141529 United States AI NIAID NIH HHS; R01 HD093761 United States HD NICHD NIH HHS; R01 AI116596 United States AI NIAID NIH HHS; UH3 OD023268 United States OD NIH HHS; T32 DK007760 United States DK NIDDK NIH HHS

Keywords: Clostridiodes difficile; ITS2; biomarker; diarrhea; gut mycobiota

Date Created: 20220722 Date Completed: 20220908 Latest Revision: 20240216

20240216

PMC9430669

10.1128/spectrum.01362-22

35867408