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.