Search Results (127)

Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization—driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding—deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome–immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases. Full article

Colostrum harbors a highly diverse microbial community, predominantly composed of genera such as Staphylococcus, Streptococcus, Lactobacillus, Bifidobacterium, and Enterococcus. The composition and diversity of this microbiota are influenced by maternal factors—including age, body mass index, lactation activity, stress levels, and gestational diabetes—as well as external factors such as mode of delivery, antibiotic exposure, diet, and geographic location. This microbial community plays a critical role in maternal and neonatal health by contributing to early gut colonization, supporting digestion, promoting immune system development, and protecting against pathogenic microorganisms through mechanisms such as antimicrobial peptide production by lactic acid bacteria. The primary aim of this study was to evaluate the impact of mode of delivery on colostrum microbiota by comparing mothers who delivered vaginally with those who underwent cesarean section. Colostrum samples from 15 mothers were subjected to DNA extraction, high-throughput sequencing, and bioinformatic analyses to characterize microbial composition and predicted functional profiles. Although substantial inter-individual variability was observed, no statistically significant differences were detected in overall microbial diversity or community structure between the two delivery groups. However, distinct bacterial taxa and functional characteristics were identified that were specific to each mode of delivery, suggesting subtle delivery-related influences on colostrum microbiota composition. Full article

Group B Streptococcus (GBS) is a component of the natural human microbiota, colonizing the genitourinary tract and the distal gastrointestinal tract. Due to its production of numerous virulence factors, GBS can cause infections in pregnant women, newborns, and immunocompromised individuals. In newborns, GBS infection may present as severe pneumonia, meningitis, or sepsis. Screening for maternal GBS colonization, combined with intrapartum antibiotic prophylaxis for colonized women, is currently regarded as the most effective strategy for preventing neonatal GBS infections. However, growing concerns regarding antibiotic resistance and the negative impact of antibiotics on the neonatal microbiome have intensified the search for alternative approaches. These include the development of a vaccine and methods to reduce vaginal colonization in pregnant women. Full article

Traditional dry-cured and fermented foods are part of the diet of many countries all over the world. These products are a source of lactic acid bacteria (LAB). Some of the LAB isolated from these products have a variety of probiotic effects on the consumers, among others, maintaining gastrointestinal homeostasis, enhancing immunity, providing antioxidant effects, preventing vaginal and urinary tract infections, and treating obesity. In addition, LAB has antagonistic properties against human pathogens and foodborne bacteria. This review summarizes methods for isolation, characterization, and selection of LAB with probiotic effects. Besides the effect of the selected probiotic LAB, focusing on gastrointestinal adhesion and colonization, and the described mechanisms of action, emphasizing their potential to advance nutritional innovations, will also be discussed. Furthermore, the advantages of the application of selected probiotic LAB in traditional dry-cured and fermented foods and in plant-based analogues will also be reviewed. Full article

Background/Objectives: Vaginitis is a prevalent inflammatory disorder of the vaginal mucosa, frequently arising from its anatomical proximity to the anorectal region and a microenvironment conducive to pathogen colonization and dysbiosis. This prospective, multicenter, randomized, third-party-blinded study assessed the efficacy and safety of a plasma vaginal cleanser (WOMEN CARE^®) employing plasma-activated water (PAW) as a non-pharmacological alternative to conventional antimicrobials for restoring vaginal homeostasis. Methods: Women aged ≥19 years with clinically suspected vaginitis were assigned to either the experimental group (WOMEN CARE^®) or the control group (standard pharmacotherapy). The primary endpoint was the proportion of participants exhibiting decreased Nugent scores between baseline and Visit 4. Results: Of 144 participants in the experimental group, 125 completed the study. The experimental group showed comparable outcomes to standard pharmacotherapy group across Nugent scores, vaginal pH, and symptoms severity, with pathogen suppression confirmed as non-inferior. Additionally, PAW exerted anti-HPV activity through a potential effect against new genotypic HPV infection. While the control group experienced antibiotic-associated adverse effects (e.g., headache, abdominal discomfort, nausea), no treatment-related adverse events occurred in the WOMEN CARE^® group. Conclusions: These results indicate that PAW vaginal cleansing provides an effective, safe, non-antibiotic approach for managing vaginitis and maintaining vaginal ecological balance. Full article

Group B Streptococcus (GBS) colonization during pregnancy is a major cause of neonatal infection, yet its microbial determinants remain unclear. This pilot study compared the vaginal and gut microbiota of late-pregnancy women with and without GBS colonization to explore potential microbial cues for peripartum risk stratification. Forty-three Japanese pregnant women (GBS-Negative = 34; GBS-Positive = 9) were enrolled at 35–37 weeks of gestation. Vaginal secretions and stool were analyzed by 16S rRNA (V3–V4) sequencing using QIIME 2 with SILVA annotation and community state type (CST) classification. Vaginal communities were mainly Lactobacillus-dominant. GBS-Positive women showed a non-significant tendency toward more L. iners-dominant CST III and fewer L. crispatus-dominant CST I compared with GBS-Negative women. Prevotella, Atopobium, and Gardnerella were significantly enriched in the GBS-Positive group (false discovery rate < 0.05), whereas gut microbial diversity and composition showed no significant differences between groups. Cross-site gut–vagina genus-level correlations were generally weak and non-significant. These findings suggest that, in late pregnancy, GBS colonization is linked to subtle shifts within Lactobacillus-dominant vaginal communities, with more L. iners and bacterial vaginosis-associated genera, rather than global microbiota disruption. The apparent shift from L. crispatus- to L. iners-dominant communities is hypothesis-generating and should be confirmed in larger cohorts. Full article

Background and Objectives: Extremely preterm infants (<28 weeks’ gestation) face high risks of morbidity and mortality, and the optimal mode of delivery for this population is debated. This retrospective study evaluated the impact of delivery mode (vaginal vs. cesarean section) on neonatal outcomes in extremely preterm infants. Materials and Methods: Ninety-two singleton births at 22 + 0 to 25 + 6 weeks of gestation were analyzed. Primary endpoints were survival to discharge; intraventricular hemorrhage (IVH); necrotizing enterocolitis (NEC); and arterial umbilical cord pH. Secondary endpoints included APGAR scores; preterm premature rupture of membranes (PPROMs); and pathological vaginal microbial colonization. Results: Survival to discharge did not differ significantly between vaginal delivery (84.8%) and cesarean section (93.5%) (p = 0.140). No significant differences were observed for NEC, APGAR scores, or umbilical arterial cord pH. IVH occurred more often after vaginal birth (47.8% vs. 30.4%, p = 0.080). In multivariable analysis, male sex was significantly associated with adverse outcome (p = 0.041); while PPROM showed a borderline association (p = 0.079). Complete antenatal corticosteroid administration was more frequent in the cesarean group (p = 0.021) and represented a relevant confounder. Conclusions: Delivery mode had no significant effect on survival in this cohort, though IVH tended to occur more frequently after vaginal birth. Male sex and complete antenatal corticosteroid exposure were key determinants of neonatal outcome. Prospective studies are needed to establish evidence-based recommendations. Full article

Background/Objectives: Fungal colonization and biofilm formation on intrauterine device (IUD) strings are known to contribute to recurrent infections and decreased contraceptive efficacy. This study aims to develop a novel approach to prevent Candida reservoir and biofilm formation on IUD strings, thereby lowering the risk of IUD-associated vulvovaginal candidiasis (VVC). Methods: Cervicovaginal samples were collected from human cervix using a sterile cytobrush, avoiding microbial contamination. Cytological examination using the Papanicolaou method was performed to detect the presence of Candida. The antifungal effect of the essential oils (EOs) was determined by broth dilution and disk diffusion methods. Antifungal and biofilm inhibitory effects of Thymus zygis (Tz) EO-coated IUD strings were determined by agar diffusion and crystal violet binding assays, while fungal growth on the coated strings was assessed using Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray (EDX) analysis. Results: Tz EO exhibited significantly lower minimum inhibitory concentration (MIC ≤ 0.06 µL/mL) and minimum fungicidal concentration (MFC = 0.24 µL/mL) values compared to Melaleuca alternifolia (Ma) EO (MIC > 0.24 µL/mL, MFC = 1.95 µL/mL), along with larger zones of inhibition (ZOI) against both Candida albicans (110.0 ± 6.0 mm vs. 91.3 ± 7.0 mm) and Candida glabrata (84.0 ± 13.1 mm vs. 50.0 ± 9.2 mm), indicating a stronger antifungal potential. On IUD strings coated with 4% (40 μL/g) Tz EO in hypromellose ointment, the biofilm formation of both C. albicans and C. glabrata strains was inhibited by 58.9% and 66.7%, respectively, as confirmed by SEM and EDX. Conclusions: Tz EO-coated IUD strings effectively inhibit Candida growth, suggesting a promising natural strategy to reduce recurrent IUD-associated fungal infections. However, before these results can be translated to clinical practice, additional research is needed. Future investigations may encompass an extended number of Candida isolates, stability and release studies of the EO in relation to the formulation, toxicity to vaginal mucosa, epithelial cells and sperm motility, and the effect on vaginal microbiotia. Full article

The increase in the incidence and antibiotic-resistant strains show a need for a broadly protective vaccine to prevent gonorrhea. OMVax has developed a combination vaccine based on native outer membrane vesicles (NOMVs) from two Neisseria meningitidis (Nm) and two Neisseria gonorrhoeae (Ng) strains. The strains had the acyl transferase LpxL1 knocked out to increase safety, and the reduction-modifiable protein was also knocked out in the Ng strains. Factor H binding protein (FHbp) mutants with reduced Factor H (FH) binding from Subfamilies A and B, respectively, were overexpressed in the Nm strains. The Ng strains individually expressed porin outer membrane protein B 1a (PorB.1a) or PorB.1b. Antibodies elicited by the Nm-Ng NOMV vaccine had SBA with a human complement against diverse Nm and Ng strains grown in the presence of Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA), had no significant reduction in serum bactericidal activity (SBA) compared to the respective individual vaccines, inhibited the adhesion to human cervical and vaginal cells in five out of six Ng strains tested, and inhibited Nm and Ng colonization in a transgenic mouse model. In conclusion, the Nm-Ng NOMV vaccine has the potential to protect against disease and inhibit colonization by diverse Nm and Ng strains, which may be an advantage for controlling the disease through vaccination, particularly in the adolescent/young adult age group. Full article

Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. Methods: A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. Results: The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a rat sarcoma virus oncogene and BRAF (B-Raf proto-oncogene), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. Conclusions: This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations. Full article

Background/Objectives: Early gut colonization by bifidobacteria, occurring more favorably in vaginally born infants than in those delivered via C-section, is crucial for maintaining overall health. The study investigated the health-promoting properties of Limosilactobacillus vaginalis BC17 both as viable cells and as postbiotics (i.e., cell-free supernatant and heat-killed cells), with the purpose of developing oral formulations to support intestinal health. Methods: The safety, effects on the adhesion of bifidobacteria and enteropathogens to intestinal cells, and anti-inflammatory properties of L. vaginalis BC17 viable cells and postbiotics were evaluated. Fast-disintegrating tablets were formulated by freeze-drying cell-free supernatant in combination with heat-killed or viable cells alongside maltodextrins. Results: The formulations were shown to be non-genotoxic and compatible with intestinal cell lines (Caco-2 and HT-29). BC17 viable cells survived in co-culture with intestinal cells up to 48 h and exhibited moderate adhesion to the cell lines. Notably, both BC17 viable cells and postbiotics enhanced the adhesion of beneficial bifidobacteria to Caco-2 cells by up to 250%, while reducing enteropathogens adhesion by 40–70%. Moreover, they exerted significant anti-inflammatory effects, reducing nitric oxide production in macrophages by 40–50% and protecting intestinal cells from SDS-induced damage. The formulations allowed administration of at least 10⁹ BC17 cells in infants and adults through easy and rapid dispersion in milk or water, or directly in the oral cavity without chewing, and preserved their functional properties for up to 3 months of storage. Conclusions: L. vaginalis BC17 viable cells and postbiotics, as well as fast-disintegrating tablets, showed promising functional and safety profiles. Although further in vivo validation is needed, this approach represents a compelling strategy for promoting gut health. Full article

The complosome controls different activities in innate immune cells and epithelial cells; however, its role in the response of VECs to Candida remains untested. In this in vitro study, we compared two clinical vaginal strains of C. albicans, namely, a Colonizing strain from a healthy woman and a strain from a patient with vulvovaginal candidiasis (VVC), for their ability to activate the complosome and release anaphylatoxins in vaginal epithelial cells (VECs). Our results show the following: (i) both strains triggered the cleavage of C3 into C3a and C3b within VECs, while infection with the Colonizing strain led to greater release of the anaphylatoxin C3a; (ii) infection with the VVC isolate led to a strong reduction in both C5 and C5a in VECs, while no increase in C5a release was observed after infection with either strain; (iii) cathepsin-family gene expression and cathepsin D activity were reduced in VECs infected with the VVC strain but not in those infected with the Colonizing strain; (iv) infection with the Colonizing strain induced a significant increase in intracellular C5aR1 while intracellular C3aR levels remained unchanged. Collectively, our data suggests the propensity of this VVC strain to inactivate the C5/C5aR1 axis and to reduce the C3/C3aR axis, dampening the activity of the complosome in VECs. These effects exerted by the VVC strain suggest a novel strategy of immune evasion by C. albicans and may open new perspectives for finding new therapeutic targets against vaginal fungal infections. Full article

Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent glycoconjugate GBS vaccine against the most prevalent serotypes and a protein subunit vaccine have completed phase two clinical trials. GBS surveillance in both maternal carriage and neonatal disease is therefore important in establishing the coverage of the potential vaccines and in setting up the basis for pre- and post-marketing surveillance. A single-site study was conducted in the years 2020–2021 on the characteristics of 325 GBS strains (serotype distribution; identification of the alpha-like protein family member; and resistance to macrolides, tetracycline, and high-level gentamicin) isolated from the vaginal/rectal site in women in late pregnancy as well as in seven cases of GBS-EOD and one case of GBS-related stillbirth occurring in the same location and time period. The study indicated that the coverage of the developing vaccines was excellent (97.2% for the hexavalent glycoconjugate vaccine and 98.7% for the alpha-like protein subunit vaccine). However, the detection of the serotypes VI, VII, and IX—not covered by current vaccine formulations—accounting for 3.0% of isolates, as well as of negative alpha-like GBS strains from maternal carriage (1.2%), should be closely monitored over time. The high rates of GBS resistance to erythromycin (33.5%) and to clindamycin (29.5% in maternal carriage and 57.1% in GBS-EOD) was mostly due to the ever-increasing spread of the multidrug-resistant ST-17 subclone of serotype III. This finding, along with the newly emerging high-level gentamicin resistance in carriers (4.0%), mainly in serotype IV strains, poses a threat for the continued effectiveness of antibiotic therapy in invasive disease. Full article

Background/Objectives: Perineal obstetrical trauma sustained during vaginal delivery has a profound impact on female quality of life. The aim of the cross-sectional study was to analyze the association between active bacterial cervical infection and group B Streptococcus (GBS) rectovaginal colonization in the 35th–37th weeks of pregnancy with the degree of delivery perineal trauma. Methods: The study included 778 women after vaginal delivery. Maternal characteristics, including age, concomitant diseases, parity, obstetrical history, and cervical swab results conducted at admission and rectovaginal bacterial swabs at the 35th–37th weeks of pregnancy, were analyzed. The rates of perineal tears were compared between the physiological and pathological cervical swab groups and between the GBS-positive and GBS-negative colonization groups. Results: At admission to delivery, active cervical infection was diagnosed in 269 (35.9%) women. After vaginal delivery, 361 (49.3%) women had an intact perineum, and 288 (39.3%), 78 (10.7%), 4 (0.6%), and 1 (0.1%) had 1st–4th-degree perineal tears, respectively. Statistical analyses of the logistic regression model found that GBS colonization at the 35th–37th weeks of pregnancy (OR 1.56, p = 0.035) and pathological flora at admission (OR 1.54, p = 0.019) were associated with perineal tears. A higher vaginal parity was found to be a protective factor (OR 0.49, p < 0.000). Conclusions: High birthweight, longer second stage of labor duration, and primiparity were associated with increased rates of perineal trauma. Active cervical infection at admission and GBS colonization at the 35th–37th weeks of pregnancy were found to be risk factors for perineal tears. A protective factor for an intact perineum was a higher number of prior vaginal deliveries. Full article

Invasive neonatal GBS infections constitute a major cause of sepsis and meningitis in Western countries. Vaginal/rectal GBS colonization during pregnancy is the main risk factor for the development of early-onset infections (GBS-EOD) in newborn by vertical transmission at birth, in addition to prematurity and stillbirth. In Italy, intrapartum antibiotic prophylaxis (IAP) to prevent GBS-EOD is offered to pregnant women who tested as GBS-positive in late pregnancy. Passive surveillance in Italy showed that a non-negligible number of GBS-EOD cases (about 50%) occurred from GBS-negative pregnant women. This finding prompted the launch of a national online survey from 15 December 2022 to 12 February 2023 to investigate the microbiological procedures followed for GBS identification in Italian public and private microbiology laboratories, the prevalence of maternal GBS colonization, and the incidence of GBS-EOD cases. The survey results demonstrated that national guidelines for the prevention of EOD-GBS cases as well as harmonization of microbiological methodologies for GBS identification in the antenatal screening are needed. Full article