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.

The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, as well as cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy history, delivery history, cesarean section, and breast feeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breastfeeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiomes, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

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.

Precocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). To explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group), and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera, and α-diversity of GM of the ICPP and PPP group were all significantly higher than that in the HC group ( ). The abundance of butyrate-producing bacteria Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus, and Alistipes was significantly higher in the ICPP group and the PPP group, and Bacteroides and Faecalibacterium showed significantly higher abundance in the HC group. The GM symbiosis network showed that both Bacteroides and Faecalibacterium were negatively correlated with these butyrate-producing bacteria. The abundances of most significantly changed genera were gradually increased from HC to PPP, and to the ICPP group, while only Bacteroides was gradually decreased. After the prediction of the metabolic pathways of the GM, the cell motility, signal transduction, and environmental adaptation were significantly enriched in the ICPP and the PPP groups ( ), while the carbohydrate metabolism pathway was significantly lower ( ). Overall, this study showed that the GM composition and predicted functional pattern of children with ICPP and PPP are different from healthy children, and PPP may be a transitional stage between ICPP and HC children, which provide a theoretical basis for clinical intervention based on GM in the treatment of PP.

Gastrointestinal (GI) disorders are very common among children with cerebral palsy. Gut microbiota has been confirmed to maintain normal GI physiological function and further contributed to cerebral palsy through the gut-brain axis. Our study was to investigate the effect of dietary fiber combined with probiotics on functional constipated children with cerebral palsy. In total, 35 patient children were enrolled and divided into general diet group (n = 14) and liquid diet group (n = 21). All the participants received Compound Dietary Fiber (CDF) for 1 month and lactic acid-producing and butyric acid-producing probiotics for 6 months. After a 1-month intervention, the frequency of spontaneous and manual defecation, and Bristol score were all significantly improved (P < 0.001). The α-diversity of the gut microbiota was significantly increased after a 1-month intervention (P < 0.05), with a higher abundance of butyric acid-producing bacteria and a lower abundance of opportunistic pathogens (P < 0.05, FDR < 0.05). However, the impersistent effect of the 6-month intervention suggested the insufficient impact of intaking probiotics alone and the short duration of CDF intervention. Moreover, although the intervention had affected the constipation symptoms equally in cerebral palsy children with a general diet and liquid diet, the general diet group showed a greater and more durable change in gut microbiota and clinical phenotypes after intervention than the liquid diet group, which indicated that longer intervention time should be considered for liquid diet children. This study not only illustrated that supplementation of dietary fiber combined with probiotics can improve functional constipation in children with cerebral palsy, but also provides guidance for optimal intervention strategy for future studies, which will further benefit cerebral palsy children.Clinical trial registration: http://www.chictr.org.cn/showproj.aspx?proj=46902, identifier: ChiCTR1900028257.