Persistent HPV infection promotes an imbalance in the vaginal flora.
A multi-approach study conducted by researchers from the Laboratory of Experimental Pathology (GIGA-Cancer, ULiege) and their partners (local and international) highlights that some innate peptides secreted by the cervical/vaginal mucosa are used by the predominant Lactobacillus species (L. crispatus, L. jensenii, L. iners) as an amino acid source. As part of a broad effort to escape the immune responses, human papillomaviruses (HPV) drastically inhibit the expression of these antimicrobial peptides, ultimately promoting an imbalance in the vaginal flora. A study published in the scientific journal Nature Communications.
The replacement of the normally dominant lactic acid bacteria (constituting over 95% of the vaginal flora) by a more diverse bacterial mixture (dominated by Gardnerella vaginalis and other anaerobic bacteria) has been considered as a risk factor for both the persistence and progression of HPV-dependent (pre)neoplastic lesions for many years. Conversely, the potential influence of HPV infections on the vaginal microbiota remained largely unknown.
This study conducted by Michael Herfs (FNRS Research Associate) and his team [more particularly Alizee Lebeau and Diane Bruyere (Televie/FRIA PhD student and now post-docs)] first showed that persistent (for several months/years) viral infections significantly increase the risk of bacterial vaginosis occurrence. Related to an inhibition of both NF-κB and Wnt/β-catenin signaling pathways (dependent on the interaction of E7 viral oncoprotein with NEMO, CK1 and β-TrCP), this phenomenon is associated with a drastic reduction in secretion of innate peptides by the host mucosa. Unexpectedly, these peptides display no antimicrobial activity on Lactobacillus species but rather, are cleaved, internalized and used as amino acid source by these lactic acid bacteria, sustaining their growth/survival.
Commonly treated with broad-spectrum antibiotics, bacterial vaginosis is well-known to have a very high recurrence rate (>50%). Therefore, some innate peptides (e.g. elafin and S100A7) physiologically secreted by the host mucosa could constitute prebiotics of choice and prove to be allies in the treatment of this pathology affecting between 15 and 30% of women.
Reference
Alizee Lebeau, Diane Bruyere, Patrick Roncarati, Paul Peixoto, Eric Hervouet, Gael Cobraiville, Bernard Taminiau, Murielle Masson, Carmen Gallego, Gabriel Mazzucchelli, Nicolas Smargiasso, Maximilien Fleron, Dominique Baiwir, Elodie Hendrick, Charlotte Pilard, Thomas Lerho, Celia Reynders, Marie Ancion, Roland Greimers, Jean-Claude Twizere, Georges Daube, Geraldine Schlecht-Louf, Françoise Bachelerie, Jean-Damien Combes, Pierrette Melin, Marianne Fillet, Philippe Delvenne, Pascale Hubert & Michael Herfs
Nature Communications, 13, Article number: 1076 (2022)
