In-depth insights into cervicovaginal microbial communities and hrHPV infections using high-resolution microbiome profiling

Abstract

The cervicovaginal microbiome (CVM) correlates with women’s cervical health, and variations in its composition are associated with high-risk human papillomavirus (hrHPV) infection outcomes. Cervicovaginal microbes have been grouped into five community state types (CSTs) based on microbial community composition and abundance. However, studying the impact of CSTs in health and disease is challenging because the current sequencing technologies have limited confident discrimination between closely related and yet functionally different bacterial species. Circular probe-based RNA sequencing (ciRNAseq) achieves high-resolution microbiome profiling and therefore provides in-depth and unambiguous knowledge about the composition of the CVM. Based on ciRNAseq profiling of a large cohort of cervical smears (n = 541), we here define subgroups of CSTs I, III, and IV based on intra-CST differences with respect to abundances of Lactobacillus acidophilus (CSTs I-A vs. I-B and CSTs III-A vs. III-B), Lactobacillus iners (CSTs I-A vs. I-B and CSTs III-A vs. III-B), and Megasphaera genomosp type 1 (CSTs IV-A vs. IV-B). Our results further support the existence of subgroups of CST IV-C that are dominant for non-Lactobacillus species and have intermediate microbial diversity. We also show that CST V is associated with uninfected conditions, and CST IV-A associates with hrHPV-induced cervical disease. In conclusion, we characterized new subdivisions of cervicovaginal CSTs, which may further advance our understanding of women’s cervical health and hrHPV-related progression to disease.

Assessing the Cervicovaginal Microbiota in the Context of hrHPV Infections: Temporal Dynamics and Therapeutic Strategies

“…Similarly, in CST IV-B, where M. genomosp type 1 is dominant, the vaginal pH is also basic, and there is production of biogenic amines, including spermidines ( Fig. 1E ) ( 46 , 73 , 74 ). Megasphaera species also take up iron available in the mucus layer for their metabolic activities ( 74 ).…”

“…These community state types (CSTs) are classified into five major groups: I, II, III, IV, and V, with CSTs I, II, III, and V presenting low diversity and having microbial dominance for Lactobacillus crispatus , Lactobacillus gasseri , Lactobacillus iners , and Lactobacillus jensenii , respectively. Colonization by Lactobacillus acidophilus further subdivides CSTs I and III into A and B subgroups ( 46 , 47 ). CST IV is characterized by high diversity, Lactobacillus depletion, and a high abundance of BV-associated bacteria, such as Gardnerella vaginalis , Megasphaera genomosp type 1 , Prevotella timonensis , and Sneathia amnii ( 17 , 46 , 48 , 49 ).…”

“…Colonization by Lactobacillus acidophilus further subdivides CSTs I and III into A and B subgroups ( 46 , 47 ). CST IV is characterized by high diversity, Lactobacillus depletion, and a high abundance of BV-associated bacteria, such as Gardnerella vaginalis , Megasphaera genomosp type 1 , Prevotella timonensis , and Sneathia amnii ( 17 , 46 , 48 , 49 ).…”

“…The prevalence of BV is high among reproductive-aged women globally, ranging from 23% to 29% ( 80 , 81 ). Other studies have investigated the composition of the CVM and have identified even more CSTs than the classical five groups ( 46 , 82 , 83 ). For instance, the vaginal colonization by L. acidophilus is characteristic of the microbial subgroup B in both CST I and CST III ( 46 , 61 ).…”

“…Other studies have investigated the composition of the CVM and have identified even more CSTs than the classical five groups ( 46 , 82 , 83 ). For instance, the vaginal colonization by L. acidophilus is characteristic of the microbial subgroup B in both CST I and CST III ( 46 , 61 ). The occurrence of L. acidophilus may promote a decrease in abundance for L. crispatus and L. iners in CSTs I and III, respectively, leading to a transitional state between both communities ( 46 ).…”