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Authors' reply re: The vaginal metabolome and microbiota of cervical HPV‐positive and HPV‐negative women: a cross‐sectional analysis

Sir, We read with great interest the recent study by Borgogna et al. which demonstrated that the vaginal metabolome of HPV women differed from HPV women in terms of several metabolites, including biogenic amines, glutathione and lipid-related metabolites. As the author mentioned, the vaginal metabolome is largely influenced by resident microbiota. For example, Srinivasan et al. found that bacterial vaginosis (BV) was associated with strong metabolic signatures across multiple pathways affecting amino acid, carbohydrate and lipid metabolism. Thus, the study should be designed to eliminate the effect of vaginal microbiota on metabolite differences. In this study, the vaginal metabolome did not cluster by HPV detection status and instead grouped broadly by bacterial composition. This can reduce the interference of vaginal anaerobic microorganisms (CST IV, ‘molecular-BV’) on metabolites. Similarly, Brotman et al. showed that Trichomonas vaginalis (TV) was associated with vaginalmicrobiota consisting of low proportions of lactobacilli and high proportions of Mycoplasma, Parvimonas, Sneathia and other anaerobes. Consider that the microbiome affects metabolites, we can infer that there are unique metabolites in TV state. Therefore, we suggest that the authors exclude patients with TV infection. Additionally, vulvovaginal candidiasis (VVC), Chlamydia trachomatis infection (CT) and BV have specific microbiomes and metabolomes. According to the taxonomic and metabolomics analysis, Ceccarani et al. found that VVC, CT and BV are characterised by a peculiar vaginal microbiome/metabolome fingerprint. Likewise, Sanches et al. characterize the lipid profile in vaginal discharge samples of women with VVC, CV or no infection or dysbiosis by liquid chromatography-mass spectrometry. Their results showed that greater concentrations were found for Gly-cochenodeoxycholic acid-7sulphate,O-adipoylcarnitine, 1-eicosyl-2heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group. We should consider the interference from yeast, pseudohyphae and blastospores. In summary, we think all participants should be examined for TV, CT and VVC. We recommend excluding the participants if they are positive for these groups. Otherwise, the authors cannot rule out interference with the results of these three pathogens.&