Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, New York, USA.
mBio. 2013 Aug 6;4(4):e00460-13. doi: 10.1128/mBio.00460-13.
We evaluated levels of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP-8) in vaginal secretions in relation to the composition of vaginal bacterial communities and D- and L-lactic acid levels. The composition of vaginal bacterial communities in 46 women was determined by pyrosequencing the V1 to V3 region of 16S rRNA genes. Lactobacilli were dominant in 71.3% of the women, followed by Gardnerella (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 proportions 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 concentrations. Moreover, vaginal concentrations of EMMPRIN and MMP-8 levels were highly correlated (P<0.0001). Taken together, the data suggest the relative proportion of L- to D-lactic acid isomers in the vagina may influence the extent of local EMMPRIN production and subsequent induction of MMP-8. The expression of these proteins may help determine the ability of bacteria to transverse the cervix and initiate upper genital tract infections.
A large proportion of preterm births (>50%) result from infections caused by bacteria 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- or L-lactic acid isomers in vaginal secretions. Elevated levels of D-lactic acid and the ratio of D- to L-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.
我们评估了阴道细胞外基质金属蛋白酶诱导剂（EMMPRIN）和基质金属蛋白酶（MMP-8）在阴道分泌物中的水平与阴道细菌群落组成和 D-和 L-乳酸水平的关系。
我们通过焦磷酸测序 16S rRNA 基因的 V1 到 V3 区，确定了 46 名女性阴道细菌群落的组成。乳酸杆菌在 71.3%的女性中占优势，其次是加德纳菌（17.4%）、链球菌（8.7%）和肠球菌（2.2%）。在乳酸杆菌占主导地位的群落中，51.5%由卷曲乳杆菌主导，36.4%由惰性乳杆菌主导，6.1%由加氏乳杆菌和詹氏乳杆菌各主导。阴道中 L-乳酸的浓度在乳酸杆菌主导的样本中略高，但大多数差异无统计学意义。与 L. iners（P<0.0001）或加德纳菌（P=0.0002）相比，含有 L. crispatus 的样本中 D-乳酸水平较高。在由各种乳酸杆菌物种组成的体外培养物中，阴道群落中 D-乳酸的相对比例与在阴道群落中发现的比例一致。乳酸水平（P<0.0001）和 L-乳酸与 D-乳酸的比例（P=0.0060），而不是 D-乳酸的浓度，也与 EMMPRIN 浓度相关。此外，阴道中 EMMPRIN 和 MMP-8 水平高度相关（P<0.0001）。
大量早产（>50%）是由起源于阴道的细菌引起的感染引起的，这需要它们穿过宫颈。影响这些感染易感性的因素尚不清楚；然而，有证据表明，基质金属蛋白酶（MMP-8）已知会改变宫颈的完整性。在这项工作中，我们表明，阴道细胞外基质金属蛋白酶诱导剂（EMMPRIN）的浓度受阴道微生物群落成员和阴道分泌物中 D-或 L-乳酸异构体浓度的影响。D-乳酸的升高水平和 D-与 L-乳酸的比值也会影响 EMMPRIN 浓度以及 MMP-8 水平。因此，乳酸异构体可能作为信号分子发挥作用，改变宿主基因表达并影响与感染相关的早产风险。
阴道中的细菌群落组成和 D-和 L-乳酸异构体的浓度可能影响 EMMPRIN 的产生和 MMP-8 的诱导，这可能有助于解释为什么某些女性比其他女性更容易发生与感染相关的早产。
