Yinhua Wu, Qiujun Zhou, Chen Wang, Xiaoyan Liu
Background: Human papillomavirus (HPV) persistence is a critical driver of malignant transformation, yet the potential association between gut microbiota composition and HPV clearance remains insufficiently explored. Methods: This study investigated the association between gut microbial features and HPV infection outcomes in patients with condyloma acuminatum (CA). Baseline fecal samples from 44 CA patients and 20 healthy controls underwent 16S rRNA gene sequencing, followed by a two-year clinical follow-up to stratify patients into HPV turn-negative (HPV_TN) and persistent-positive (HPV_PP) groups. Bioinformatic analyses, including alpha/beta diversity metrics, linear discriminant analysis Effect Size (LEfSe), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) functional prediction, and receiver operating characteristic (ROC) curve evaluation, were employed. Results: CA patients exhibited significantly increased microbial richness and distinct beta diversity compared to controls. Notably, LEfSe analysis identified Bacteroides stercoris as a significant biomarker enriched in the HPV_PP group, while Bacteroides vulgatus showed nominally higher abundance in the HPV_PP group. ROC analysis yielded area under the curves (AUCs) of 0.733 for B. stercoris and 0.729 for B. vulgatus, with a combined two-species logistic regression model achieving an AUC of 0.743. Furthermore, Mantel's test and Spearman correlation analysis linked specific microbial shifts to clinical parameters including HPV persistence status. Conclusions: This exploratory study identifies associations between gut microbiota composition and HPV persistence in CA patients. B. stercoris represents the most robust candidate microbial signature, while B. vulgatus provides supplementary evidence. These findings generate hypotheses for future prospective and mechanistic studies investigating whether gut microbiota modulation could influence HPV clearance. The enrichment of B. stercoris and B. vulgatus may represent candidate microbial signatures requiring independent external validation.