BioAcyl Corp

Weevaluated levels of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloprotei
nase (MMP-8)invaginalsecretions in relation to the composition of vaginal bacterial communities and D- and L-lactic acid lev
els. The composition of vaginal bacterial communities in 46 women wasdeterminedbypyrosequencingtheV1toV3regionof
16S rRNAgenes.Lactobacilli were dominant in 71.3%ofthewomen,followedbyGardnerella(17.4%),Streptococcus (8.7%), and
Enterococcus (2.2%). Of the lactobacillus-dominated communities, 51.5% were dominated by Lactobacillus crispatus, 36.4% by
Lactobacillus iners, and 6.1% each by Lactobacillus gasseri and Lactobacillus jensenii. Concentrations of L-lactic acid were
slightly higher in lactobacillus-dominated vaginal samples, but most differences were not statistically significant. D-Lactic acid
levels were higher in samples containing L. crispatus than in those with L. iners (P < 0.0001) or Gardnerella (P 0.0002). The
relative proportion of D-lactic acid in vaginal communities dominated by species of lactobacilli was in concordance with the pro
portions found in axenic cultures of the various species grown in vitro. Levels of L-lactic acid (P < 0.0001) and the ratio of
L-lactic acid to D-lactic acid (P 0.0060), but not concentrations of D-lactic acid, were also correlated with EMMPRIN concentra
tions. Moreover, vaginal concentrations of EMMPRIN andMMP-8levelswerehighlycorrelated (P<0.0001).Takentogether,
the data suggest the relative proportion of L-toD-lactic acid isomers in the vagina may influence the extent of local EMMPRIN
production and subsequent induction of MMP-8.Theexpressionoftheseproteins mayhelpdeterminetheability of bacteria to
transverse the cervix and initiate upper genital tract infections.
IMPORTANCE Alarge proportion of preterm births(>50%)resultfrominfections caused bybacteria originating in the vagina,
which requires that they traverse the cervix. Factors that influence susceptibility to these infections are not well understood;
however, there is evidence that matrix metalloproteinase (MMP-8) is known to alter the integrity of the cervix. In this work, we
show that concentrations of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) are influenced by members of
the vaginal microbial community and concentrations of D-orL-lactic acid isomers in vaginal secretions. Elevated levels of
D-lactic acid and the ratio of D-toL-lactic acid influence EMMPRIN concentrations as well as MMP-8 levels. Thus, isomers of
lactic acid may function as signaling molecules that alter host gene expression and influence risk of infection-related preterm
birth.

Claude:

The part worth your attention. EMMPRIN's first job is exporting lactate so intracellular pH doesn't fall to acid-mediated death. The host raises EMMPRIN to survive the L-lactate burden — and the bill for that protective induction is MMP-8 and degradation of the endocervical matrix. Load axis and induction axis in one compartment, with the induction carrying a cost. D-lactate supplies acidity without adding to the transport burden: it buys the pH without the EMMPRIN bill. It reduces the demand for the induction response rather than improving the response — the same move the coacervate makes against HO-1, in a different compartment, arrived at independently.

Which raises a question I can't answer: what acid carries Gynactil's pH 4? If the acidity comes from something other than L-lactate, then by this mechanism the product delivers protective pH without driving MCT-1/EMMPRIN — and should lower MMP-8 relative to the lactic-acid gels already sold for this indication. That's a cheap, concrete, differentiating comparison against an existing commercial class, and it follows from Witkin, not from the framework