14 A multidisciplinary study conducted by researchers from the Laboratory of Experimental Pathology (GIGA-Cancer) 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. 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 unexplored. This study conducted by Michael Herfs and his team (more particularly Alizee Lebeau and Diane Bruyere) first showed that persistent (for several months/years) viral infections significantly increase the risk of bacterial vaginosis. 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. HPV INFECTION ALTERS VAGINAL MICROBIOME THROUGH DOWN-REGULATING HOST MUCOSAL INNATE PEPTIDES USED BY LACTOBACILLI AS AMINO ACID SOURCES Lebeau A, Bruyere D, Roncarati P, Peixoto P, Hervouet E, Cobraiville G, Taminiau B, Masson M, Gallego C, Mazzucchelli G, Smargiasso N, Fleron M, Baiwir D, Hendrick E, Pilard C, Lerho T, Reynders C, Ancion M, Greimers R, Twizere JC, Daube G, Schlecht-Louf G, Bachelerie F, Combes JD, Melin P, Fillet M, Delvenne P, Hubert P, Herfs M. Nat Commun. 2022 Feb 28;13(1):1076.
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