Dynamics of the microbiota in patients with Clostridioides difficile: Recurrence, treatment, sex, and immunosuppression

BACKGROUND: Alterations in the gut microbiome are central to the pathogenesis and recurrence of Clostridioides difficile infection (CDI). OBJECTIVE: To evaluate intestinal microbiome changes during CDI and their association with recurrence, sex, age, and immunosuppression. METHODS: Patients from the CDI-ANCRAID-SEICV cohort were consecutively enrolled. Stool samples were obtained at diagnosis (Dx), end of treatment (ET), and eight weeks post-treatment (8W) or upon recurrence. Microbiota composition was analyzed by 16S rRNA sequencing using QIIME2 and R. Outcomes were compared by demographics, immunosuppression, and treatment (vancomycin [VNC], vancomycin-bezlotuzumab [VNC-BZL], fidaxomicin [FDX]). RESULTS: Among 143 patients, non-recurrent cases showed higher biodiversity at 8W versus diagnosis (H p = 0.002, ASVs p < 0.001), unlike recurrent cases. Diversity decreased with VNC (H p > 0.001, ASVs p < 0.001) but was preserved with FDX (H p = 0.15). Recovery of Shannon diversity was limited in women (p = 0.50) and immunocompromised patients (p = 0.31). At ET, Fusobacteria and Verrucomicrobiota were less abundant in recurrent than non-recurrent cases (0.77%, 0.53% vs 3.43%, 3.50%). FDX-treated samples showed higher Bacteroidetes (31.33%) compared to VNC (5.23%) or VNC-BZL (3.12%). Women exhibited increased Firmicutes abundance (p = 0.034). CONCLUSIONS: Restoration of microbial diversity correlates with CDI resolution. FDX preserves gut microbiota better than VNC or VNC-BZL. Women and immunocompromised patients demonstrate impaired microbiota recovery.

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Publication Details

Journal
PLoS Pathogens
Published
2026-04-06
DOI
https://doi.org/10.1371/journal.ppat.1014063
Primary Topic
Clostridium difficile and Clostridium perfringens research
Type
article
Field-Weighted Citation Impact
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article

Dynamics of the microbiota in patients with Clostridioides difficile: Recurrence, treatment, sex, and immunosuppression

María Tasias, José Manuel Ramos, Francisco Jover, David Vinuesa-García et al.
PLoS Pathogens
Clostridium difficile and Clostridium perfringens research
article

Dynamics of the microbiota in patients with Clostridioides difficile: Recurrence, treatment, sex, and immunosuppression

María Tasias, José Manuel Ramos, Francisco Jover, David Vinuesa-García, Rocío Herrero, Juan José Castón, Nicolás Merchante, Pilar González-de-la-Aleja, Ana-Isabel Aller, Reinaldo Espíndola-Gómez, Jara Llenas-García, Maria Paz Ventero, Miguel Nicolás Navarrete-Lorite, Juan Carlos Rodríguez, Concepcion Gil, María-Dolores Valverde-Fredet, Francisco J. Martínez Marcos, Miguel Rodríguez-Fernández, Marta Trigo, Cristina Gomez-Ayerbe, Monica Parra, Esperanza Merino De Lucas, Ines Portillo, Eva M. León, Silvia Otero, María Dolores Vallés García, Iryna Tyshkovska
article en

Abstract

BACKGROUND: Alterations in the gut microbiome are central to the pathogenesis and recurrence of Clostridioides difficile infection (CDI). OBJECTIVE: To evaluate intestinal microbiome changes during CDI and their association with recurrence, sex, age, and immunosuppression. METHODS: Patients from the CDI-ANCRAID-SEICV cohort were consecutively enrolled. Stool samples were obtained at diagnosis (Dx), end of treatment (ET), and eight weeks post-treatment (8W) or upon recurrence. Microbiota composition was analyzed by 16S rRNA sequencing using QIIME2 and R. Outcomes were compared by demographics, immunosuppression, and treatment (vancomycin [VNC], vancomycin-bezlotuzumab [VNC-BZL], fidaxomicin [FDX]). RESULTS: Among 143 patients, non-recurrent cases showed higher biodiversity at 8W versus diagnosis (H p = 0.002, ASVs p < 0.001), unlike recurrent cases. Diversity decreased with VNC (H p > 0.001, ASVs p < 0.001) but was preserved with FDX (H p = 0.15). Recovery of Shannon diversity was limited in women (p = 0.50) and immunocompromised patients (p = 0.31). At ET, Fusobacteria and Verrucomicrobiota were less abundant in recurrent than non-recurrent cases (0.77%, 0.53% vs 3.43%, 3.50%). FDX-treated samples showed higher Bacteroidetes (31.33%) compared to VNC (5.23%) or VNC-BZL (3.12%). Women exhibited increased Firmicutes abundance (p = 0.034). CONCLUSIONS: Restoration of microbial diversity correlates with CDI resolution. FDX preserves gut microbiota better than VNC or VNC-BZL. Women and immunocompromised patients demonstrate impaired microbiota recovery.

PLoS PathogensVol. 22(4)
Universitat de Miguel Hernández d'Elx (ES), Instituto de Salud Carlos III (ES), Hospital Universitari i Politècnic La Fe (ES), Hospital Universitario Virgen Macarena (ES), Hospital Universitari Sant Joan D'Alacant (ES), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES), Instituto de Investigación Biosanitaria de Granada (ES), Hospital Universitario Reina Sofía (ES), Hospital Juan Ramón Jiménez (ES), Instituto de Biomedicina de Sevilla (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Hospital Marina Baixa (ES), Hospital Clínico Universitario Virgen de la Victoria (ES), Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) (ES)
Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, Agencia Estatal de Investigación, Conselleria de Cultura, Educación y Ciencia, Generalitat Valenciana, European Social Fund
Gender equality
Openalex Percentile: Top 27%
Clostridium difficile and Clostridium perfringens research
DOIOpen Access PDFOpenAlex
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