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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Microbiol.</journal-id>
<journal-title>Frontiers in Microbiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Microbiol.</abbrev-journal-title>
<issn pub-type="epub">1664-302X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmicb.2017.01815</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Microbiology</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Fuochi</surname> <given-names>Virginia</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn003"><sup>&#x02020;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/472098/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Li Volti</surname> <given-names>Giovanni</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="author-notes" rid="fn003"><sup>&#x02020;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/246511/overview"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Furneri</surname> <given-names>Pio Maria</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/338097/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Microbiology Section, Department of Biomedical and Biotechnological Sciences, University of Catania</institution> <country>Catania, Italy</country></aff>
<aff id="aff2"><sup>2</sup><institution>Medical Biochemistry Section, Department of Biomedical and Biotechnological Sciences, Biological Tower, University of Catania</institution> <country>Catania, Italy</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Omry Koren, Bar-Ilan University, Israel</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Rebeca Mart&#x000ED;n, INRA Centre Jouy-en-Josas, France; Suleyman Yildirim, School of International Medicine, Istanbul Medipol University, Turkey</p></fn>
<fn fn-type="corresp" id="fn001"><p>&#x0002A;Correspondence: Pio Maria Furneri <email>furneri&#x00040;unict.it</email></p></fn>
<fn fn-type="other" id="fn002"><p>This article was submitted to Microbial Symbioses, a section of the journal Frontiers in Microbiology</p></fn>
<fn fn-type="other" id="fn003"><p>&#x02020;These authors have contributed equally to this work.</p></fn></author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>09</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection">
<year>2017</year>
</pub-date>
<volume>8</volume>
<elocation-id>1815</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>07</month>
<year>2017</year>
</date>
<date date-type="accepted">
<day>06</day>
<month>09</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2017 Fuochi, Li Volti and Furneri.</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Fuochi, Li Volti and Furneri</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" journal-id="Front Microbiol" journal-id-type="nlm-ta" vol="7" page="1936" xlink:href="28008325" ext-link-type="pubmed">A commentary on <article-title>Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?</article-title> by Miller, E. A., Beasley, D. E., Dunn, R. R., and Archie, E. A. (2016). Front. Microbiol. 7:1936. doi: <object-id>10.3389/fmicb.2016.01936</object-id></related-article>
<kwd-group>
<kwd><italic>Lactobacillus</italic> spp.</kwd>
<kwd>vaginal microbiome</kwd>
<kwd>pH</kwd>
<kwd>estrogens</kwd>
<kwd>lactic Acid</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="30"/>
<page-count count="3"/>
<word-count count="1907"/>
</counts>
</article-meta>
</front>
<body>
<p>Vaginal microbiota is involved in the homeostasis of mammal female&#x00027;s physiological conditions (Ja&#x00161;arevi&#x00107; et al., <xref ref-type="bibr" rid="B9">2015</xref>), avoiding vaginal infections such as aerobic vaginitis, bacterial vaginosis, and candidiasis (Vitali et al., <xref ref-type="bibr" rid="B28">2007</xref>; Tempera and Furneri, <xref ref-type="bibr" rid="B25">2010</xref>; Heczko et al., <xref ref-type="bibr" rid="B7">2015</xref>). To this regard, the <italic>genus Lactobacillus</italic> plays a major role in women vagina, exerting its beneficial functions by lactic acid and bacteriocins production (Fuochi et al., <xref ref-type="bibr" rid="B5">2017</xref>; Tachedjian et al., <xref ref-type="bibr" rid="B24">2017</xref>). Furthermore, the very low pH (4.5&#x02013;6.0) of the genital tract should be taken into due account in protection of the host (Wylie and Henderson, <xref ref-type="bibr" rid="B30">1969</xref>). Miller et al. have analyzed and put together possible hypotheses (Figure <xref ref-type="fig" rid="F1">1</xref>) in order to explain the important correlation between Lactobacilli dominance and vaginal pH in human species. They further elaborated their own theory as a possible explanation of that peculiarity. In particular, the authors suggested that the high level of glycogen, present in the human females&#x00027; vagina but not in other mammal species, could be an energy source for <italic>Lactobacillus</italic> growth. Such presence should be due to the human diet particularly rich in starch. Although, we do share Miller&#x00027;s exhaustive hypotheses and conclusions, we would like to point out additional aspects that have to be taken into due account. On the one hand, vaginal epithelium is rich in glycogen as well as cervico-vaginal mucus is rich in mucins and glycoproteins and therefore there are very high levels of nutrients allowing colonization and dominance of lactobacilli (Mart&#x000ED;n Rosique et al., <xref ref-type="bibr" rid="B12">2008</xref>; Mirmonsef et al., <xref ref-type="bibr" rid="B14">2014</xref>; Nunn and Forney, <xref ref-type="bibr" rid="B18">2016</xref>). On the other hand, high glycogen concentrations are dependent on the high levels of estrogen (Mirmonsef et al., <xref ref-type="bibr" rid="B15">2016</xref>). Moreover, Gorodeski et al. (<xref ref-type="bibr" rid="B6">2005</xref>) provided a further explanation for vaginal pH: vaginal cells seem to contribute to luminal acidity through an active and estrogen-dependent proton secretion throughout the woman&#x00027;s life.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Miller et al. (<xref ref-type="bibr" rid="B13">2016</xref>): a schematic representation.</p></caption>
<graphic xlink:href="fmicb-08-01815-g0001.tif"/>
</fig>
<p>Furthermore, women&#x00027;s life is characterized by continuous physiological changes, from their birth through the reproductive age to menopause, and during all these phases the vaginal microbiota and vaginal epithelium radically change (Paavonen, <xref ref-type="bibr" rid="B19">1983</xref>). The fertile age is characterized by monthly ovulation and therefore high estrogenic levels which, also thanks to the action of proton pumps (Aldunate et al., <xref ref-type="bibr" rid="B2">2015</xref>; Mirmonsef et al., <xref ref-type="bibr" rid="B15">2016</xref>), lead the vaginal lumen to be particularly acid. The combined effect of the presence of glycogen and low pH render provide the best conditions for the growth of <italic>Lactobacillus</italic>.</p>
<p>When the woman reaches the menopause this pattern changes significantly because estrogens are no longer present and the glycogen level decreases leading to a significant modification of vaginal microbiota characterized in particular by a decrease in the amount of lactobacilli (Roccasalva et al., <xref ref-type="bibr" rid="B20">2002</xref>; Hickey et al., <xref ref-type="bibr" rid="B8">2012</xref>; Nunn and Forney, <xref ref-type="bibr" rid="B18">2016</xref>; Shen et al., <xref ref-type="bibr" rid="B22">2016</xref>). The importance of estrogens is further substantiated by the evidence that restoring estrogen levels results in improved trophic conditions of the vaginal epithelium restoring all the benefits arising from such condition (Paavonen, <xref ref-type="bibr" rid="B19">1983</xref>; Roccasalva et al., <xref ref-type="bibr" rid="B20">2002</xref>; Gorodeski et al., <xref ref-type="bibr" rid="B6">2005</xref>; Lien et al., <xref ref-type="bibr" rid="B11">2009</xref>; Hickey et al., <xref ref-type="bibr" rid="B8">2012</xref>; Nunn and Forney, <xref ref-type="bibr" rid="B18">2016</xref>; Shen et al., <xref ref-type="bibr" rid="B22">2016</xref>).</p>
<p>As far as the diet theory is concerned, different vaginal ecotypes should exist according to the different types of diets in the same way as different habits and practices (Lien et al., <xref ref-type="bibr" rid="B11">2009</xref>; Hickey et al., <xref ref-type="bibr" rid="B8">2012</xref>), and this would be accentuated in cases of intolerance or allergies. In particular, in patients with celiac disease, women might have a very different vaginal microbiota, and therefore it would be very interesting to carry out a study to confirm a closer relationship between diets and vaginal microbiota.</p>
<p>In conclusion, we believe that Miller&#x00027;s observations are of great interest for the field, but in our opinion the explanation is more related to the mechanistic theories (reproductive phase hypothesis and common function hypothesis) than it is to the others. Nevertheless, we believe that uniqueness of human vaginal microbiome is due to all five theories (including Miller&#x00027;s hypothesis), intersecting each other, and from which it is impossible to extrapolate one single mechanistic theory.</p>
<sec id="s1">
<title>Author contributions</title>
<p>All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.</p>
<sec>
<title>Conflict of interest statement</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
</sec>
</body>
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