The influence of the oral microbiota in full-term pregnant women on immune regulation during pregnancy.

BACKGROUND: This study aims to conduct a preliminary exploration of the correlation between the oral microbiota of full-term pregnant women and both local placental immunity and the systemic immune system of the mother. METHODS: A total of 26 pregnant women participated in this study, with samples collected from oral swabs, placental tissue, and peripheral venous blood. High-throughput sequencing was used to examine the oral microbial community. Flow cytometry was employed to assess immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid bead chip technology were utilized to detect cytokines in both placental tissue and peripheral venous blood. RESULTS: In placental tissue, The oral microbial community is primarily negatively correlated with placental CD3+CD4+CD8+T cells and positively correlated with placental IL-5. In the peripheral blood, The oral microbial community is primarily positively correlated with maternal systemic immune parameters, including CD3+CD4+ T cells and the CD4+/CD8+ ratio, as well as positively correlated with peripheral IL-18. CONCLUSIONS: The oral microbiota of full-term pregnant women participates in the regulatory function of the maternal immune system. Meanwhile, the oral microbial community may also be an important factor mediating local immune regulation in the placenta.

From whole genomes to probiotic candidates: A study of potential lactobacilli strains selection for vaginitis treatment.

Vaginitis, characterized by pathogenic invasion and a deficiency in beneficial lactobacilli, has recognized lactobacilli supplementation as a novel therapeutic strategy. However, due to individual differences in vaginal microbiota, identifying universally effective Lactobacillus strains is challenging. Traditional methodologies for probiotic selection, which heavily depend on extensive in vitro experiments, are both time-intensive and laborious. The aim of this study was to pinpoint possible vaginal probiotic candidates based on whole-genome screening. We sequenced the genomes of 98 previously isolated Lactobacillus strains, annotating their genes involved in probiotic metabolite biosynthesis, adherence, acid/bile tolerance, and antibiotic resistance. A scoring system was used to assess the strains based on their genomic profiles. The highest-scoring strains underwent further in vitro evaluation. Consequently, two strains, Lactobacillus crispatus LG55-27 and Lactobacillus gasseri TM13-16, displayed an outstanding ability to produce d-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity against Gardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa compared to reference Lactobacillus strains. Their resilience to acid and bile environments highlights the potential for oral supplementation. Oral and vaginal administration of these two strains were tested in a bacterial vaginosis (BV) rat model at various doses. Results indicated that combined vaginal administration of these strains at 1 × 106 CFU/day significantly mitigated BV in rats. This research offers a probiotic dosage guideline for vaginitis therapy, underscoring an efficient screening process for probiotics using genome sequencing, in vitro testing, and in vivo BV model experimentation.

The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy.

BACKGROUND: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy. METHODS: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively. RESULTS: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes. CONCLUSION: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

Prevalence of and risk factors for chlamydia in female outpatients with genital tract infections: a nationwide multi-center, cross-sectional study in China.

Introduction: Chlamydia trachomatis is the etiological agent of the commonest sexually transmitted bacterial infection. This study aimed to examine the prevalence of genital chlamydia and associated risk factors in Chinese female outpatients with genital tract infections. Methods: A prospective, multicenter epidemiological study of genital chlamydia prevalence in 3008 patients with genital tract infections in 13 hospitals in 12 provinces of China was performed between May 2017 and November 2018. Vaginal secretion specimens were collected for the clinical diagnosis of vaginitis, whereas cervical secretion specimens were tested for Chlamydia trachomatis and Neisseria gonorrhoeae. All patients participated in a one-on-one cross-sectional questionnaire interview. Results: Totally 2,908 participants were included. The prevalence rates of chlamydia and gonococcal infections in women with genital tract infections were 6.33% (184/2908) and 0.01% (20/2908), respectively. Multivariate analysis showed high risk factors for chlamydia were premarital sex behavior, first sexual intercourse before the age of 20 and bacterial vaginosis. Discussion: Given that most chlamydia cases are asymptomatic and no vaccine is currently available, chlamydia prevention strategies should include behavioral interventions as well as early screening programs to identify and treat individuals with genital tract infections, especially those with the above identified risk factors.

Maternal sepsis in pregnancy and the puerperal periods: a cross-sectional study.

Maternal sepsis is a life-threatening condition and ranks among the top five causes of maternal death in pregnancy and the postpartum period. Herein, we conducted a retrospective study on sepsis cases to explain the related risk factors by comparing them with bloodstream infection (BSI) and control maternities. In total, 76 sepsis cases were enrolled, and 31 BSI and 57 maternal cases of the same age but with neither sepsis nor BSI were set as controls. Genital tract infection (GTI) and pneumonia were the two most common infection sources in both sepsis (22 cases, 29% and 29 cases, 38%) and BSI cases (18 cases, 58% and 8 cases, 26%). Urinary tract infection (UTI)/pyelonephritis (9 cases, 12%) and digestive infection cases (11 cases, 14%) only existed in the sepsis group. Significantly different infection sources were discovered between the sepsis-death and sepsis-cure groups. A higher proportion of pneumonia and a lower proportion of GTI cases were present in the sepsis-death group (17 cases, 45% pneumonia and 9 cases, 24% GTI) than in the sepsis-cure group (12 cases, 32% pneumonia and 13 cases, 34% GTI). In addition, although gram-negative bacteria were the dominant infectious microorganisms as previously reported, lower proportion of gram-negative bacteria infectious cases in sepsis (30 cases, 50%) and even lower in sepsis-death group (14 cases, 41%) was shown in this study than previous studies. As expected, significantly greater adverse maternal and fetal outcomes, such as higher maternal mortality (26.3% vs. 0% vs. 0%), higher fetal mortality (42.2% vs. 20.8% vs. 0%), earlier gestational age at delivery (26.4 ± 9.5 vs. 32.3 ± 8.1 vs. 37.7 ± 4.0) and lower newborn weight (1,590 ± 1287.8 vs. 2859.2 ± 966.0 vs. 3214.2 ± 506.4), were observed in the sepsis group. This study offered some potential pathogenesis and mortality risk factors for sepsis, which may inspire the treatment of sepsis in the future.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Maternal Group B Streptococcal Rectovaginal Colonization after Intrapartum Antibiotic Prophylaxis.

Maternal rectovaginal colonization with Group B Streptococcus (GBS) during labor is a prerequisite for neonatal early-onset GBS disease. Intrapartum antibiotic prophylaxis (IAP) has been proven to prevent GBS perinatal infection, while there are few studies on the evaluation of the effectiveness of different antibiotic prophylaxis regimens. This study aimed to assess the maternal rectovaginal GBS colonization status after IAP, antimicrobial susceptibility and maternal and neonatal outcomes among women administered different antibiotic prophylaxis regimens. A prospective study was conducted between June 2018 and June 2022. GBS carriers identified at 35-37 weeks of gestation were provided IAP (penicillin, cefazolin or clindamycin) at delivery based on the local protocol for GBS prevention. Rectovaginal samples were obtained from participants again after delivery. Antimicrobial susceptibility testing in GBS isolates was performed using the broth microdilution method. A total of 295 cases were included in this study. In the postpartum re-examination for GBS, the overall negative rectovaginal culture rate was 90.8% (268/295). Women who received cefazolin prophylaxis had the highest negative culture rate (95.2%, 197/207), which was followed by those who received penicillin (80.7%, 67/83) and clindamycin (80.0%, 4/5) (p = 0.001). All GBS isolates achieved sensitivity to penicillin and cefazolin, whereas resistance to clindamycin was shown in 21.4% of the strains. There were no significant differences in maternal and neonatal outcomes among the IAP groups. The use of IAP is highly effective in reducing the maternal rectovaginal GBS colonization. Cefazolin may offer equivalent efficacy and safety compared to standard penicillin prophylaxis.

Risk Factors for Macrosomia in Multipara: A Multi-Center Retrospective Study.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.