Lactobacillus Modulates Chlamydia Infectivity and Genital Tract Pathology in vitro and in vivo

Abstract

Since we previously reported that women infected with chlamydia had a significant overall reduction in Lactobacillus in the vagina microbiota as compared to those uninfected individuals; the interactions between the altered Lactobacillus and Chlamydia trachomatis, on the other hand, need to be elucidated. Here, we employed both in vitro and in vivo models to evaluate the effects of this changed Lactobacillus on Chlamydia infection. We found that L. iners, L. crispatus, L. jensenii, L. salivarius, L. gasseri, L. mucosae, and L. reuteri all significantly reduced C. trachomatis infection in a dose- and time-dependent manner. The strongest anti-Chlamydia effects were found in L. crispatus (90 percent reduction), whereas the poorest was found in L. iners (50 percent reduction). D (–) lactic acid was the key component in Lactobacillus cell-free supernatants (CFS) to inactivate Chlamydia EBs, showing a positive correlation with the anti-Chlamydia activity. The effects of D (–) lactic acid were substantially attenuated by neutralizing the pH value to 7.0. In vivo, mice intravaginally inoculated with Lactobacillus mixtures (L. crispatus, L. reuteri, and L. iners at a ratio of 1:1:1), but not single Lactobacillus, after genital Chlamydia infection, significantly attenuated the levels of Chlamydia live organism shedding in both the lower genital tract and the intestinal tract, reduced cytokines production (TNF-α, IFN-γ, and IL-1β) in the vagina, and lessened upper genital tract inflammation and pathogenicity. Taken together, these data demonstrate that Lactobacillus inhibits Chlamydia infectivity both in vivo and in vitro, providing useful information for the development of Lactobacillus as adjunctive treatment in Chlamydia infection.

Role of D(−)-Lactic Acid in Prevention of Chlamydia trachomatis Infection in an In Vitro Model of HeLa Cells

“…L. crispatus was chosen because it is known to be able to produce both isomers of LA. In contrast, L. reuteri , which is known to be very abundant in the gut, is a far less effective producer of D(−)-LA [ 15 ]. In particular, the isolate used in the present study produces only L(+)-LA isomer.…”

“…Other authors showed that culture supernatants of L. crispatus and L. jensenii modulated the expression of several genes related to cell proliferation, including a decrease in CCND1 and HER-1. In contrast, L. iners , which is unable to produce D(−)-LA, failed to downregulate these genes and protect against infection with CT [ 15 , 28 ]. Moreover, previous studies have shown that EGFR is required for the internalization of chlamydial EBs into host cells [ 37 ].…”

“…Since both D(−) and L(+) isomers are present in vaginal fluid and their relative amounts depend on which lactobacillus species predominates [ 15 , 16 , 17 ], we decided to conduct a comprehensive study to investigate the role of the two LA isomers in the reduction in CT infectivity.…”

Ovarian Cancer and the Microbiome: Connecting the Dots for Early Diagnosis and Therapeutic Innovations—A Review

“…Studies have indicated that Chlamydia can ascend to the upper female genital tract, inducing inflammation and damage, potentially leading to pelvic inflammatory disease (PID) and an increased risk of ovarian cancer [ 43 , 44 , 45 , 46 ]. Certain Lactobacillus strains, including Lactobacillus crispatus , have demonstrated significant bactericidal effects against Chlamydia trachomatis [ 47 ]. In particular, Lactobacillus crispatus exhibits 90% bactericidal activity, mainly attributed to lactic acid production [ 47 , 48 , 49 ].…”

“…Certain Lactobacillus strains, including Lactobacillus crispatus , have demonstrated significant bactericidal effects against Chlamydia trachomatis [ 47 ]. In particular, Lactobacillus crispatus exhibits 90% bactericidal activity, mainly attributed to lactic acid production [ 47 , 48 , 49 ]. This suggests a potential risk reduction for ovarian cancer through the modulation of Chlamydia by Lactobacillus .…”