Lactobacillus iners

What was studied?

An imbalance of the vaginal microbiome and dysregulation of cytokines are associated with spontaneous preterm birth (sPTB). To date, the relationship between the vaginal microbiome, cytokines, and sPTB remains unclear in the Chinese population. Herein, we conducted a nested case-control study using data from a prospective cohort of 749 Chinese women with a singleton pregnancy who were enrolled between 16 and 28 weeks of pregnancy. Cases consisted of individuals experiencing sPTB (n = 38), while controls were selected randomly at a 4:1 ratio to cases (n = 152). Compared to the term group, the sPTB group exhibited significantly increased abundance of vaginal Aerococcus christensenii, Gardnerella swidsinskii, and Lactobacillus iners, along with elevated levels of interleukin (IL)-1β, IL-6, and IL-12p70 in vaginal fluid (P < 0.05). Least absolute shrinkage and selection operator (LASSO) regression identified L. iners, G. swidsinskii, and IL-6 as significant risk factors for sPTB, with adjusted odds ratios (ORs) (95% CI) of 1.57 (1.06-2.34), 1.45 (1.03-2.05), and 2.05 (1.43-2.93), respectively. Finally, a logistic regression model for sPTB was established incorporating L. iners, G. swidsinskii, and IL-6, which yielded an area under the receiver operating characteristic curve (AUC) of 0.73. These findings suggest that alterations in the vaginal microbiome and cytokine levels may contribute to sPTB in the Chinese population.IMPORTANCEPreterm birth (PTB) is the leading cause of death in children under 5 years of age, of which about 70% were spontaneous ones (sPTB); while genitourinary infections are implicated in 25-40% of sPTB cases. Previous studies have revealed some features of vaginal microbiome and cytokines related to sPTB: increased richness and diversity, increased levels of Lactobacillus iners, BV-associated bacteria, low abundance of L. crispatus, and high levels of pro-inflammatory cytokines. However, there were also some inconsistent findings, and little is known in the Chinese population. This study confirmed the correlations between vaginal microbiome, cytokines, and sPTB in Chinese pregnant women. Specifically, elevated vaginal L. iners, G. swidsinskii, and IL-6 levels were significantly associated factors, which may help to identify women at high risk of sPTB.

What was studied?

This study examined gut microbiota composition in children with three rare, monogenic intoxication-type inborn errors of metabolism: methylmalonic acidemia (MMA), propionic acidemia (PA), and maple syrup urine disease (MSUD). All affected children were on medically supervised, protein-restricted diets, which the authors note may itself alter the gut microbiome. Fecal samples were analyzed using 16S rRNA sequencing, and both alpha and beta diversity were assessed. The authors highlight that no prior study had characterized gut microbiota in MMA or MSUD specifically.

Who was studied?

The cohort consisted of eight children with these disorders (five with MMA, one with PA, and two with MSUD), all following a protein-restricted diet under medical supervision. Eleven age-matched healthy children served as controls. This is a small, real-world pediatric clinical sample rather than a public dataset, reflecting the rarity of these inborn errors of metabolism.

What were the most important findings?

Patients with MMA, PA, and MSUD showed significantly altered gut microbiota composition compared to healthy controls. Alpha diversity was reduced in patients, with significantly lower Chao1 and observed OTU indices, indicating decreased microbial richness. Beta diversity analysis showed distinct clustering, meaning the overall community structure differed significantly between patient and control groups. The abstract does not mention Faecalibacterium prausnitzii, butyrate, or specific anti-inflammatory commensal taxa.

What are the greatest implications of this study?

These findings suggest that children managing MMA, PA, or MSUD with strict protein-restricted diets may develop a less rich and structurally distinct gut microbiome relative to healthy peers. Because this is the first data available for MMA and MSUD, it establishes a baseline for future research into how dietary protein restriction and disease biology jointly shape the microbiome in these disorders. Given the very small sample size, these results should be viewed as preliminary and hypothesis-generating rather than conclusive. Larger studies are needed to clarify whether microbiota alterations relate to disease pathophysiology, dietary restriction, or both, and whether they carry clinical consequences.

What was studied?

UNLABELLED: Backed by advancements in technologies like microbial sequencing, many studies indicate that the vaginal microbiome is a key marker of female reproductive health. However, further studies are still needed to investigate the correlation between vaginal microbiota (VMB) and outcomes of assisted reproductive technology (ART). Therefore, this study compared the VMB of two types of infertile women undergoing in vitro fertilization (IVF) with normal control women during the implantation window period and investigated the effects of VMB characteristics on IVF outcomes. Vaginal swabs from IVF patients (n = 85) were collected before embryo transfer (ET), and vaginal swabs from normal control women (n = 37) were collected during the 6-8 days of ovulation detection. Results showed differences in the vaginal community structure between infertile women with polycystic ovary syndrome (PCOS) and with tubal factor infertility (TFI) undergoing IVF treatment. The results revealed a higher relative abundance of Lactobacillus iners in the non-pregnant group compared with the pregnant group. The results also demonstrated the abundance of Pseudomonas spp. in both non-pregnant groups of infertile women. The findings suggested that the VMB composition affects the IVF outcomes and that the pre-ET high abundance of L. iners may potentially indicate an IVF failure. The abundance of Pseudomonas spp. in the vagina may be an adverse factor for ART pregnancy. IMPORTANCE: Many studies suggest that vaginal microbiota (VMB) may affect in vitro fertilization-embryo transfer (IVF-ET) outcomes. Assessing VMB before embryo transfer can optimize timing for better assisted reproductive technology (ART) results. This study examined VMB distribution in infertile women undergoing ART using 16S rRNA sequencing. Results revealed that VMB structure impacted ART outcomes in women with polycystic ovary syndrome (PCOS) and tubal factor infertility (TFI) before embryo transfer ([less than or equal to] 24 hours). Lactobacillus iners and Pseudomonas spp. were identified as adverse factors for post-ET pregnancy. The study also showed differences in pre-ET VMB between normal women and women with PCOS and TFI during the ovulatory window. These findings highlight the importance of considering VMB composition to optimize embryo transfer timing and personalize ART treatment based on infertility type, improving the chances of success.

What was studied?

This meta-analysis examined the gut microbiome in obese children with metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). Researchers searched electronic databases for studies providing shotgun metagenomic sequencing data on the gut microbiome in children with obesity, with or without MASLD or MASH. The analysis combined data from multiple existing studies with an additionally recruited cohort to compare microbiome composition and function across disease states.

Who was studied?

The pooled analysis included obese children with MASLD (n = 153) and MASH (n = 70), compared against obese children without liver disease (n = 58) and healthy controls (n = 132). This population was assembled from nine identified studies plus one additionally recruited cohort, all using shotgun metagenomic sequencing. The study therefore draws on a multi-cohort pediatric dataset rather than a single trial population.

What were the most important findings?

Fecal microbiomes of children with MASLD and MASH differed significantly in alpha- and beta-diversity compared to obese and healthy children (p < 0.001). Faecalibacterium prausnitzii and Prevotella copri were differentially abundant across the obese, MASLD, and MASH groups. Machine-learning models (XGBoost and random forest) accurately distinguished MASLD from obesity (AUROC 87%) and MASH from MASLD (AUROC 89%), with pathway-abundance-based models performing similarly well (81% and 88%, respectively). Increasing hepatic fibrosis was accompanied by further gut microbiome alteration and a concomitant rise in Prevotella copri abundance (p = 0.0082).

What are the greatest implications of this study?

The findings suggest that gut microbiome composition, including shifts in species such as Faecalibacterium prausnitzii and Prevotella copri, tracks with the progression from obesity to MASLD to MASH and fibrosis severity in children. The high predictive accuracy of microbiome-based machine-learning models points to potential non-invasive tools for staging pediatric liver disease. These results also support the gut microbiome as a plausible target for future diagnostic or therapeutic strategies in pediatric metabolic liver disease.

What was studied?

This study investigated the relationship between vaginal microbiota and women's health conditions in 95 Chinese pregnant women in their third trimester. We conducted vaginal metagenomic analysis, examining species, functional pathways, and genes, and utilized correlation and LEfSe analyses to link microbiota to health conditions. Results revealed that healthy participants exhibited higher levels of Lactobacillus iners, with its abundance associated with tetrahydrofolate biosynthesis pathways. They also possessed more glycosyltransferase and ErmB antibiotic resistance genes compared to women with diagnosed conditions. Comparative genomics demonstrated that L. iners strains linked to bacterial vaginosis (BV) possessed more genes encoding biofilm-associated YhgE/Pip domain-containing proteins than healthy-associated strains. Notably, three BV-associated L. iners strains exhibited stronger biofilm formation abilities than four healthy-associated strains isolated in this study. Also, four out of seven L. iners strains inhibited the growth of Gardnerella vaginalis. Overall, L. iners may help maintain vaginal ecosystem stability in Chinese pregnant women.

What was studied?

The oral and gut microbiota had been shown to control bone metabolism and have a strong correlation with osteoporosis. However, to reveal the oral and gut bacteria characteristics in osteoporosis, further studies are still needed to investigate the relationship between oral and gut microbiota diversity and bone health in OVX-induced osteoporotic rats versus Sham-operated (Sham) rats. This study analyzed the oral and gut microbiota in OVX and Sham rats using 16S rRNA gene sequencing. We compared microbial diversity and composition between the two groups. There was an inverse association found between the number of bacterial taxa and bone mineral density (BMD) readings. The OVX group had considerably higher estimated diversity of both oral and gut microbiota than the Sham group. Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteriota were the dominant phyla in both groups. The OVX group had a reduced ratio of Firmicutes in oral and gut microbiota compared to the Sham group (p <  0.05). OVX rats had a higher proportion of oral Bacteroidota but a lower proportion of gut microbiota. They also had a substantial drop in Lactobacillus in both oral and gut microflora (p <  0.01). The crosstalk between oral and gut microbiota may be important in the development of osteoporosis. Identifying novel biomarkers in the oral and gut microbiota could provide more information in osteoporosis and the intricate oral-gut-bone health interaction.

What was studied?

Presently, 20-40% of pregnant women are colonized with Streptococcus agalactiae, which is commonly referred to as Group B Streptococcus (GBS). Numerous studies have demonstrated the association of GBS colonization with adverse pregnancy outcomes and neonatal infectious diseases. However, few studies have explored the complex interactions between GBS and other reproductive tract microbes.

Who was studied?

This study employed a retrospective case‒control design. The research subjects included 53 pregnant women at 35-37 weeks of gestation who received treatment at Shenyang Women and Infants Hospital between November 1, 2022, and July 1, 2024 (GBS culture-positive group vs. GBS culture-negative group: 22 vs. 31). Chi-square tests and multiple logistic regression analyses were performed to identify factors associated with genital tract colonization in GBS patients. Additionally, reproductive tract swabs from 53 pregnant women were subjected to 16 S rRNA microbiome analysis using the Illumina NovaSeq platform.

What were the most important findings?

Our analysis revealed that factors such as premature rupture of membranes, preterm delivery, diabetes mellitus, vaginal cleanliness, elevated leukocyte count in the vaginal discharge, and fungal colonization were associated with GBS colonization. The presence of both shared and unique amplicon sequence variants (ASVs) was observed between the GBS culture-negative and GBS culture-positive groups. The beta diversity values revealed significant differences in species composition between the groups. The GBS culture-positive group presented greater species richness, reduced homogeneity, and a notable reduction in the abundance of Lactobacillus.

What are the greatest implications of this study?

GBS shares intricate relationships with other bacterial taxa within the reproductive tract. Understanding and optimizing the composition and dynamics of the reproductive tract microbiota can provide theoretical support and guidance for clinical prevention and treatment of GBS colonization, thereby reducing adverse pregnancy outcomes and neonatal infectious diseases in patients with GBS colonization.

What was studied?

The process of in vitro fertilization-embryo transfer (IVF-ET) induces a maternal supraphysiological estradiol environment during embryo implantation and early development. Estrogen is crucial in modulating the colonization of microbiota within the vaginal epithelium. However, the impact of supraphysiological estradiol levels on the vaginal microbiome and the relationship with pregnancy outcomes remains unclear.

What were the most important findings?

The study aimed to characterize the vaginal microbiota under supraphysiological hormonal conditions. A total of 67 patients undergoing fresh embryo transfer were divided into three groups based on their peak estradiol levels: high-estradiol (HE) group (E2 > 11,000 pmol/L), median-estradiol (ME) group (E2 5,000-11,000 pmol/L), and low-estradiol (LE) group (E2 < 5,000 pmol/L). Twenty-five patients undergoing frozen-thawed embryo transfer were categorized into natural cycle (NC) group and hormone replacement cycle (HRT) group according to endometrial preparation protocols. Using 16S rRNA sequencing, we found that the vaginal microbiome exhibited variations with changes in peak estradiol levels. The elevated estradiol levels during ovarian stimulation or exogenous estrogen supplementation, significantly reduced alpha diversity, altered beta diversity within the vaginal microbiome, and shifted the vaginal community state types (CSTs) in Chinese infertile women toward Lactobacillus-dominant profiles, resembling those observed in most Asian women previously. However, the reproductive outcomes were not improved by these variations. The Streptococcus_anginosus and Akkermansia abundance correlated with estradiol levels positively, whereas Escherichia-Shigella showed a negative correlation. The abundance of Streptococcus, Atopobium, and Bifidobacterium on the day of embryo transfer may serve as predictors for adverse pregnancy outcomes, as determined by calculating the area under the curve (AUC) values.

What are the greatest implications of this study?

Supraphysiological estradiol levels induced by IVF-ET significantly alter vaginal microbiota and shift the CSTs in Chinese infertile women toward patterns of most Asian women. The Lactobacillus dominance under supraphysiological estradiol conditions does not help improve assisted reproductive outcomes. The abundance of Streptococcus, Atopobium, and Bifidobacterium on the day of embryo transfer may serve as predictors for adverse pregnancy outcomes. Among them, Streptococcus correlates positively with peak estradiol levels and may act as a microbial mediator impairing reproductive success under hyperestrogenic conditions. However, further larger-scale researches are needed to identify and elucidate the potential mechanisms.

What was studied?

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

What was studied?

This study investigated the microbial and metabolic profile of the gut-lung axis in children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). The researchers used an integrated multi-omics approach, analyzing metabolites and microbiota from both the gut and lower respiratory tract. Their goal was to characterize how gut and pulmonary microbiome and metabolome profiles relate to each other in PAH-CHD and to explore the potential diagnostic value of these profiles.

Who was studied?

The study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease. Participants were drawn from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. This design allowed direct comparison of gut and lower respiratory tract samples between affected children and healthy controls.

What were the most important findings?

The gut and pulmonary microbiota of children with PAH-CHD showed an increased abundance of beneficial symbionts compared to healthy individuals. These microbial shifts were closely linked to accompanying metabolite changes, indicating coordinated alterations across the gut-lung axis. The abstract does not specify particular taxa such as Salmonella, Salmonella enterica, typhoid-associated organisms, or the Enterobacteriaceae, so no claims about those groups can be made from this study.

What are the greatest implications of this study?

The findings support the idea that the gut-lung axis is disrupted in pediatric PAH-CHD and may play a role in disease progression through immune and metabolic pathways. Because distinct microbiome and metabolome signatures were identified, these profiles could potentially serve as aids in diagnosing PAH-CHD. Further validation would be needed before such profiles could be used clinically, but the results point toward the microbiome as a relevant factor in this cardiopulmonary condition.

What was studied?

Annually, in India, 13% of all newborns are preterm, accounting for 23.4% of preterm birth (PTB) globally. The composition and diversity of the vaginal microbiome have a notable degree of ethnic inequality. For understanding differences in vaginal microbiome composition and functions between adverse and normal pregnancy, we have collected, processed and sequenced 600 high vaginal swab (HVS) samples across the three trimesters of pregnancy from 140 women who delivered at term and 60 women who delivered PTB, adopting a targeted metagenomics approach. The microbial signatures in HVS samples showed Lactobacillus genera to be highly abundant in term birth (TB), while in early pregnancy the abundances of Gardnerella, Atopobium, and Sneathia were found to be high in PTB. We further extended our analysis, identified specific microbial genomic signatures, and developed a dipstick assay for rapid identification of PTB-associated microbiota in HVS samples in low-resource settings.

What was studied?

Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the cause and effect of the condition. The present study characterizes the microbial pathogenesis involved in developing cervical cancer. Relative species abundance assessment identified Firmicutes, Actinobacteria, and Proteobacteria dominating the phylum level. A significant increase in Lactobacillus iners and Prevotella timonensis at the species level revealed its pathogenic influence on cervical cancer progression. The diversity, richness, and dominance analysis divulges a substantial decline in cervical cancer compared to control samples. The β diversity index proves the homogeneity in the subgroups' microbial composition. The association between enriched Lactobacillus iners at the species level, Lactobacillus, Pseudomonas, and Enterococcus genera with cervical cancer is identified by Linear discriminant analysis Effect Size (LEfSe) prediction. The functional enrichment corroborates the microbial disease association with pathogenic infections such as aerobic vaginitis, bacterial vaginosis, and chlamydia. The dataset is trained and validated with repeated k-fold cross-validation technique using a random forest algorithm to determine the discriminative pattern from the samples. SHapley Additive exPlanations (SHAP), a game theoretic approach, is employed to analyze the results predicted by the model. Interestingly, SHAP identified that the increase in Ralstonia has a higher probability of predicting the sample as cervical cancer. New evidential microbiomes identified in the experiment confirm the presence of pathogenic microbiomes in cervical cancer vaginal samples and their mutuality with microbial imbalance.

What was studied?

This study investigated the duodenal mucosa-associated microbiota and its surrounding microenvironment in relation to hyperglycemia, an area far less studied than stool microbiota in metabolic disease. The researchers compared paired stool and duodenal microbial samples between hyperglycemic and normoglycemic individuals. They also assessed the duodenal microenvironment directly by measuring tissue oxygen saturation, serum inflammatory markers, and zonulin as a marker of gut permeability. The goal was to determine whether duodenal, rather than stool, microbial changes track more closely with glycemic status.

Who was studied?

The study population consisted of 33 subjects with hyperglycemia, defined as HbA1c of 5.7% or higher and fasting plasma glucose above 100 mg/dl, compared against 21 normoglycemic subjects. Both groups contributed paired stool and duodenal samples, allowing direct comparison of microbiota across two body sites within the same individuals. No further demographic details are given in the abstract.

What were the most important findings?

Hyperglycemic subjects had a significantly higher duodenal bacterial count than normoglycemic subjects, along with increased pathobionts and reduced beneficial flora. This bacterial overload correlated with elevated serum zonulin and higher TNF-alpha, suggesting a link to increased gut permeability and inflammation. The hyperglycemic group also showed reduced duodenal oxygen saturation, higher total leukocyte count, and lower IL-10, indicating a systemic proinflammatory state. Notably, unlike stool flora, duodenal bacterial profile variability was specifically associated with glycemic status.

What are the greatest implications of this study?

These findings suggest the duodenal microbiome and its local microenvironment, rather than stool alone, may play a distinct role in the pathogenesis of hyperglycemia and prediabetes. The association between bacterial overload, reduced oxygen saturation, and systemic inflammatory markers points to a possible mechanistic pathway linking small intestinal dysbiosis to metabolic dysfunction. This work highlights the duodenum as an underexplored but potentially important site for understanding and possibly intervening in early glycemic disturbances.

What was studied?

Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients.

Who was studied?

CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients.

What were the most important findings?

Differential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score >4, adj. p-value <0.05). Functional analyses showed distinct microbial metabolic pathways in CRCs compared to normal tissues within the racial/ethnic groups. Egyptian CRCs, compared to normal tissues, showed lower l-methionine biosynthesis and higher galactose degradation pathways.

What are the greatest implications of this study?

Our findings showed altered mucosa-associated microbiome profiles of CRCs and their metabolic pathways across racial/ethnic groups. These findings provide a basis for future studies to link racial/ethnic microbiome differences with distinct clinical behaviors in CRC.

What was studied?

Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment.

Who was studied?

A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients.

What were the most important findings?

The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera.

What are the greatest implications of this study?

Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.

What was studied?

The vaginal microbiome protects the female genital tract from various diseases, such as vaginitis, a vaginal inflammation characterized by abnormal discharge, itching, and pain. To evaluate the clinical relationship between the vaginal microbiome and the pathophysiology of recurrent vaginitis (RV), we investigated the microbiome taxonomic profile (MTP) in the vaginal samples of Korean female patients with RV.

Who was studied?

Forty women of reproductive age diagnosed with RV were enrolled. The vaginal MTP of patients was analyzed using 16S ribosomal RNA gene sequencing, and the results were compared with that of healthy women (n = 100). Further, the association of the vaginal community state type (CST) with the clinical characteristics was analyzed.

What were the most important findings?

The species abundance of MTP was significantly lower in patients with RV than in healthy women (p < 0.05), whereas species evenness and diversity were significantly higher in patients with RV than in healthy individuals (p < 0.05). The proportion of the most common vaginal Lactobacillus spp. was significantly lower in the MTP of patients with RV than healthy women (p < 0.01). The beta diversity distance was also significantly different between patients with RV patients and healthy individuals (p = 0.001). Based on the CST, the MTP of 40 RV samples was categorized as follows: 21 (52.5%) for CST IV, 8 (20.0%) for CST III, 5 (12.5%) for CST I, 2 (5.0%) for CST II, 1 for (2.5%) for CST V, and 3 (7.5%) for mixed CST. Patients with underlying uterine diseases (uterine leiomyoma, adenomyosis, and endometrial polyps; n = 17) showed higher species richness and diversity than those without (n = 23; p < 0.05).

What are the greatest implications of this study?

Changes in the species abundance and microbial diversity in the vagina were strongly associated with RV. A low proportion of Lactobacillus spp. was found in patients with RV than in healthy women. The abundance and diversity of bacterial taxa were significantly higher in patients with underlying gynecologic disease than those without. Our study offers an insight into the nature of the vaginal microbiome and proposes that surveying the vaginal microbiome is valuable for detecting and treating gynecologic diseases in the future.

What was studied?

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195-0.656; P < .05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004-0.072; P < .001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb.

What was studied?

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.

What was studied?

Preterm premature rupture of membranes (PPROM) is a common pregnancy complication. Yet, the main cause of PPROM remains poorly understood. In this study, we used 16S rRNA gene sequencing technology to identify the differences in vaginal microbiota between pregnant women with PPROM and those who delivered at term.

Who was studied?

Vaginal samples were collected from 48 patients with PPROM and 54 age- and gestational age-matched pregnant women who delivered at term (controls). The vaginal microbiota of the two groups was compared using 16S rRNA gene sequencing of the V3-V4 regions.

What were the most important findings?

The vaginal microbial composition of the PPROM group was significantly different from that of the control group. Our results showed that the diversity of vaginal microbiota in patients with PPROM increased compared with controls. The relative abundance of Lactobacillus iners, Gardnerella vaginalis, Prevotella bivia, Ochrobactrum sp., Prevotella timonensis, and Ureaplasma parvum were more abundant in patients with PPROM, while Lactobacillus crispatus and Lactobacillus gasseri were more abundant in controls. Ochrobactrum sp., Prevotella timonensis, and Gardnerella vaginalis, could serve as biomarkers for PPROM. Finally, we proposed several metabolic pathways, including PWY-6339, PWY-6992, and PWY-7295.

What are the greatest implications of this study?

PPROM is characterized by vaginal microbial dysbiosis. The dysbiotic vaginal microbiota signatures in patients with PPROM include a higher bacterial diversity, decreased autochthonous bacteria, and increased pathogenic bacteria. These results may be beneficial for developing biomarkers for screening and early diagnosis of PPROM and may provide effective preventative treatments.

What was studied?

This single-center study profiled the gut mucosa-associated microbiome of Kenyan colorectal cancer (CRC) patients and healthy volunteers. Researchers used 16S rRNA sequencing to characterize microbial community composition, examining alpha and beta diversity, differential taxa abundance, and predicted microbial metabolic profiles. The study also evaluated associations between microbiome profiles and patient age, motivated by rising and increasingly early-onset CRC incidence in Kenya.

Who was studied?

The cohort consisted of 18 CRC patients and 18 healthy controls recruited at the Moi Teaching and Referral Hospital, Moi University, in Kenya. This population was chosen because microbiome studies in Kenyan CRC patients are rare, despite CRC incidence rates tripling in the country between 1997 and 2017. The hospital has also observed an increase in CRC diagnoses among younger patients.

What were the most important findings?

Alpha diversity did not differ significantly between CRC patients and healthy controls, but beta diversity metrics showed clear dissimilarities in overall microbial community structure between the two groups. The most notably underrepresented species in the CRC group were Prevotella copri and Faecalibacterium prausnitzii, an anti-inflammatory, butyrate-associated commensal. The abstract also points to an association with bacterial glutamate degradation pathways as part of the CRC-associated microbial signature.

What are the greatest implications of this study?

The findings suggest that gut microbiome dysbiosis, marked by loss of key commensals like Faecalibacterium prausnitzii and Prevotella copri, may contribute to CRC pathobiology in a Kenyan population that has been understudied in microbiome research. Because overall diversity was preserved while community composition shifted, compositional and functional changes rather than diversity loss appear more relevant to CRC in this setting. These results support further investigation of microbiome signatures, including glutamate metabolism pathways, as potential contributors to the rising and increasingly early-onset CRC burden in Sub-Saharan Africa.

What was studied?

Human milk contains abundant commensal bacteria that colonize and establish the infant's gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, 'early' (6-46 days postpartum, n = 29) or 'late' (109-184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ -1 SD (early: n = 18; late: n = 14) and HCAZ < -1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ -1 SD and HCAZ < -1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ -1 SD and HCAZ < -1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR < 0.05) between HCAZ ≥ -1 SD and HCAZ < -1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ -1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ < -1 SD group at late lactation had more differentially abundant taxa associated with environmentally and 'potentially opportunistic' species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.

What was studied?

Streptococcus agalactiae or group B Streptococcus (GBS) asymptomatically colonizes the genitourinary tracts of up to 30% of pregnant women. Globally, GBS is an important cause of neonatal morbidity and mortality. GBS has recently been linked to adverse pregnancy outcomes. The potential interactions between GBS and the vaginal microbiome composition remain poorly understood. In addition, little is known about the vaginal microbiota of pregnant Egyptian women.

What were the most important findings?

Using V3-V4 16S rRNA next-generation sequencing, we examined the vaginal microbiome in GBS culture-positive pregnant women (22) and GBS culture-negative pregnant women (22) during the third trimester in Ismailia, Egypt. According to the alpha-diversity indices, the vaginal microbiome of pregnant GBS culture-positive women was significantly more diverse and less homogenous. The composition of the vaginal microbiome differed significantly based on beta-diversity between GBS culture-positive and culture-negative women. The phylum Firmicutes and the family Lactobacillaceae were significantly more abundant in GBS-negative colonizers. In contrast, the phyla Actinobacteria, Tenericutes, and Proteobacteria and the families Bifidobacteriaceae, Mycoplasmataceae, Streptococcaceae, Corynebacteriaceae, Staphylococcaceae, and Peptostreptococcaceae were significantly more abundant in GBS culture-positive colonizers. On the genus and species levels, Lactobacillus was the only genus detected with significantly higher relative abundance in GBS culture-negative status (88%), and L. iners was the significantly most abundant species. Conversely, GBS-positive carriers exhibited a significant decrease in Lactobacillus abundance (56%). In GBS-positive colonizers, the relative abundance of the genera Ureaplasma, Gardnerella, Streptococcus, Corynebacterium, Staphylococcus, and Peptostreptococcus and the species Peptostreptococcus anaerobius was significantly higher. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the metabolism of cofactors and vitamins, phosphatidylinositol signaling system, peroxisome, host immune system pathways, and host endocrine system were exclusively enriched among GBS culture-positive microbial communities. However, lipid metabolism KEGG pathways, nucleotide metabolism, xenobiotics biodegradation and metabolism, genetic information processing pathways associated with translation, replication, and repair, and human diseases (Staphylococcus aureus infection) were exclusively enriched in GBS culture-negative communities.

What are the greatest implications of this study?

Understanding how perturbations of the vaginal microbiome contribute to pregnancy complications may result in the development of alternative, targeted prevention strategies to prevent maternal GBS colonization. We hypothesized associations between inferred microbial function and GBS status that would need to be confirmed in larger cohorts.

What was studied?

HPV persistent infection is a main event leading to the development of cervical intraepithelial neoplasia and cervical cancer. Earlier to distinguish HPV persistent and transient infection is meaningful but the methods are limited. This study used 16S rDNA sequencing to determine the cervicovaginal microbiota of HPV persistent infection, transient infection and health women. Sequences analysis was performed and according to subsequent statistical analysis, the structure of cervicovaginal microbiota of healthy and transient infection individuals is relatively single, Firmicutes occupy the main composition. However, that of the HPV persistent infection presented a complicated trend and the abundance of Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria was higher. The significance p-values of the average species abundance of Firmicutes, Proteobacteria and Bacteroides between HPV persistent and transient infection groups were 0.003, 0.018 and 0.005, respectively. The study also found 36 biomarkers of cervicovaginal microbiota dysbiosis for LDA score>4 among different groups. At genus level, Prevotella, Sphingomonas and Anaerococcus correlated with HPV persistent infection. At species level, Lactobacillus iners correlated with HPV transient infection. Besides, local immune microenvironment was changed with cervicovaginal microbiota dysbiosis. Interleukin-6 and TNF-α were significantly upregulated in cervical secretions from HPV persistent infection compared with those from transient infection and healthy women. Peripheral blood Regulatory T cells and myeloid-derived suppressor cells in patients with HPV persistent infection were also significantly increased. In conclusion, this study identified cervicovaginal microbiota dysbiosis closely related to HPV persistent infection, which provided a new idea and method for the prevention of cervical cancer.

What was studied?

Recent research studies are showing breast tissues as a place where various species of microorganisms can thrive and cannot be considered sterile, as previously thought. We analysed the microbial composition of primary tumour tissue and normal breast tissue and found differences between them and between multiple breast cancer phenotypes. We sequenced the transcriptome of breast tumours and normal tissues (from cancer-free women) of 23 individuals from Slovakia and used bioinformatics tools to uncover differences in the microbial composition of tissues. To analyse our RNA-seq data (rRNA depleted), we used and tested Kraken2 and Metaphlan3 tools. Kraken2 has shown higher reliability for our data. Additionally, we analysed 91 samples obtained from SRA database, originated in China and submitted by Sichuan University. In breast tissue, the most enriched group were Proteobacteria, then Firmicutes and Actinobacteria for both datasets, in Slovak samples also Bacteroides, while in Chinese samples Cyanobacteria were more frequent. We have observed changes in the microbiome between cancerous and healthy tissues and also different phenotypes of diseases, based on the presence of circulating tumour cells and few other markers.

What was studied?

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized. Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level. Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients. Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.

What was studied?

Vaginal microbiota-host interactions are linked to preterm birth (PTB), which continues to be the primary cause of global childhood mortality. Due to population size, the majority of PTB occurs in Asia, yet there have been few studies of the pregnancy vaginal microbiota in Asian populations. Here, we characterized the vaginal microbiome of 2689 pregnant Chinese women using metataxonomics and in a subset (n = 819), the relationship between vaginal microbiota composition, sialidase activity and leukocyte presence and pregnancy outcomes. Vaginal microbiota were most frequently dominated by Lactobacillus crispatus or L. iners, with the latter associated with vaginal leukocyte presence. Women with high sialidase activity were enriched for bacterial vaginosis-associated genera including Gardnerella, Atopobium and Prevotella. Vaginal microbiota composition, high sialidase activity and/or leukocyte presence was not associated with PTB risk suggesting underlying differences in the vaginal microbiota and/or host immune responses of Chinese women, possibly accounting for low PTB rates in this population.

What was studied?

Preterm birth remains the main contributor to early childhood mortality. The vaginal environment, including microbiota composition, might contribute to the risk of preterm delivery. Alterations in the vaginal microbial community structure might represent a risk factor for preterm birth. Here, we aimed to (a) investigate the association between preterm birth and the vaginal microbial community and (b) identify microbial biomarkers for risk of preterm birth. Microbial DNA was isolated from vaginal swabs in a cohort of 69 women enrolled at hospital admission for their delivery. Microbiota was analyzed by high-throughput 16S rRNA sequencing. While no differences in microbial diversity measures appeared associated with the spontaneous preterm and full-term outcomes, the microbial composition was distinct for these groups. Differential abundance analysis showed Lactobacillus species to be associated with full-term birth whereas an unknown Prevotella species was more abundant in the spontaneous preterm group. Although we studied a very miscegenated population from Brazil, our findings were similar to evidence pointed by other studies in different countries. The role of Lactobacillus species as a protector in the vaginal microbiome is demonstrated to be also a protector of spontaneous preterm outcome whereas the presence of pathogenic species, such as Prevotella spp., is endorsed as a factor of risk for spontaneous preterm delivery.

What was studied?

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV.

Who was studied?

This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R.

What were the most important findings?

At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22-0.79), V1 fungal diversity, OR = 0.90 (0.82-1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62-0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03-1.38) was shown to be predictive of progression to CIN2+.

What are the greatest implications of this study?

This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+.

What was studied?

Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.

What was studied?

Endometriosis (EMS) is a multifactorial disease that affects 10%-15% women of reproductive age and is associated with chronic pelvic pain and infertility. The pathogenesis of EMS has not been consistently explained until now. In this study, we involved 36 endometriosis patients and 14 control subjects who performed laparoscopic surgery due to gynecological benign tumor. The samples from lower third of vagina (CL), posterior vaginal fornix (CU), cervical mucus (CV), endometrium (ET) and peritoneal fluid (PF), were collected and sequenced by 16S rRNA amplicon. The continuous change of the microbiota distribution was identified along the reproductive tract. The flora in lower reproductive tract (CL, CU) were dominated by Lactobacillus. Significant difference of the community diversity began showing in the CV of EMS patients and gradually increased upward the reproductive tract. It indicates the microbiota in cervical samples is expected to be an indicator for the risk of EMS. This study also highlights the decreasing of Lactobacillus in vaginal flora and the increasing of signature Operational Taxonomic Units (OTUs) in transaction zone (CV) and upper reproductive tract (ET, PF) of EMS patients, which reflect the alteration of microbial community associated with EMS, participation of specific colonized bacteria in the EMS pathogenesis and relationship between microbiota and development of disease.

What was studied?

The vaginal microbiota of healthy women typically has low diversity, which increases after perturbations. Among these, lifestyle associated with certain sexual and antimicrobial practices may be associated with higher diversity. To test this hypothesis, we characterized the vaginal microbiota in the cervicovaginal and introital sites in sexually active Amerindians (N = 82) spanning urbanization, and in urban mestizos (N = 29), in the Venezuelan Amazonas. HPV status was also considered. Sampling was performed in an urban gradient from remote villages to a town, and women were individually classified by the degree of urbanization (low, medium, and high). Amerindian cervicovaginal and introital microbiota diversity were not associated with major changes in urbanization or ethnicity. There was a non-significant trend of increased diversity with urbanization, with a few taxa found overrepresented in urban Amerindians (Brevibacterium linens and Peptoniphilus lacrimalis) or mestizos (Mobiluncus mulieris and Prevotella sp.). Among all women, cervicovaginal and introital samples clustered, respectively, in four and two community state types (CSTs), where most profiles were dominated by Lactobacillus iners, Gardnerella vaginalis or were highly diverse profiles. HPV status did not associate with microbial diversity. In conclusion, no association was found between urban level and the vaginal microbiome in Amerindian women, and little difference was found between ethnicities. L. iners and high diversity profiles, associated with vaginal health outcomes, prevail in these populations.

What was studied?

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15-19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

What was studied?

To explore differences in the vaginal microbiome between preterm and term deliveries.

Who was studied?

Nested case-control study in 3D cohort (design, develop, discover). Quebec, Canada. To assess the vaginal microbiome by sequencing the V4 region of the 16S ribosomal RNA (rRNA) gene in swabs self-collected during early pregnancy.

What were the most important findings?

Lactobacillus gasseri/ Lactobacillus johnsonii (coefficient -5.36, 95% CI -8.07 to -2.65), Lactobacillus crispatus (99%)/ Lactobacillus acidophilus (99%) (-4.58, 95% CI -6.20 to -2.96), Lactobacillus iners (99%)/ Ralstonia solanacearum (99%) (-3.98, 95% CI -6.48 to -1.47) and Bifidobacterium longum/ Bifidobacterium breve (-8.84, 95% CI -12.96 to -4.73) were associated with decreased risk of early but not late preterm birth. Six vaginal CSTs were identified: four dominated by Lactobacillus; one with presence of bacterial vaginosis-associated bacteria (Gardnerella vaginalis, Atopobium vaginae and Veillonellaceae bacterium) (CST IV); and one with nondominance of Lactobacillus (CST VI). CST IV was associated with increased risk of early (4.22, 95% CI 1.24-24.85) but not late (1.63, 95% CI 0.68-5.04) preterm birth, compared with CST VI.

What are the greatest implications of this study?

Lactobacillus gasseri/L. johnsonii, L. crispatus/L. acidophilus, L. iners/R. solanacearum and B. longum/B. breve may be associated with decreased risk of early preterm birth. A bacterial vaginosis-related vaginal CST versus a CST nondominated by Lactobacillus may be associated with increased risk of early preterm birth.

What was studied?

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals.IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.

What was studied?

While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36γ was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.

What was studied?

We investigated the association between HPV infection and bacterial microbiota composition in the placenta, uterine cervix and mouth in thirty-nine women. HPV DNA genotyping of 24 types was conducted using Multimetrix®. Microbiota composition was characterized by 16S rRNA gene sequencing. HPV DNA was detected in 33% of placenta, 23% cervical and 33% oral samples. HPV16 was the most frequent type in all regions. HPV infection was associated with higher microbiota richness (p = 0.032) in the mouth but did not influence microbial diversity or richness in other samples. HPV infection was associated with higher abundance of Lactobacillaceae (p = 0.0036) and Ureaplasma (LDA score > 4.0, p < 0.05) in the placenta, Haemophilus (p = 0.00058) and Peptostreptococcus (p = 0.0069) genus in the cervix and Selenomonas spp. (p = 0.0032) in the mouth compared to HPV negative samples. These data suggest altered bacterial microbiota composition in HPV positive placenta, cervix and mouth. Whether the changes in bacterial microbiota predispose or result from HPV remains to be determined in future studies.

What was studied?

This study examined the bacterial community composition of the bronchial airway, sampled by protected bronchial brushing, in relation to atopic asthma. The researchers used 16S rRNA gene sequencing to characterize the bronchial bacterial microbiome and inferred community-level functional profiles from the sequencing data. They compared microbiome composition across groups and examined associations with clinical and inflammatory features, including type 2-related inflammation markers and the change in airway hyperresponsiveness following six weeks of inhaled fluticasone treatment.

Who was studied?

The study included 42 adults with steroid-naive atopic asthma, 21 adults with atopy but no asthma, and 21 nonatopic healthy control subjects. All participants underwent bronchial brushing to obtain airway samples for bacterial profiling. The asthmatic group had not yet received corticosteroid treatment at the time of initial sampling, allowing comparison before and after six weeks of fluticasone.

What were the most important findings?

The bronchial microbiome differed significantly among the three groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas genera compared with the atopy-only and healthy control groups. These compositional differences suggest that microbiome features are more closely tied to the asthma phenotype itself than to atopy or aeroallergen sensitization alone.

What are the greatest implications of this study?

By comparing steroid-naive asthmatics, atopic non-asthmatics, and healthy controls, the study helps disentangle whether bronchial microbiome changes reflect asthma, atopy, or corticosteroid treatment. Enrichment of specific bacterial genera in asthmatic airways points to potential microbial targets or biomarkers relevant to asthma pathophysiology. The examination of microbiome relationships to corticosteroid responsiveness also raises the possibility that airway bacterial composition could inform understanding of treatment response in asthma.

What was studied?

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

What was studied?

Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44%±5.26%) and Clostridium cocleatum (0.10%±0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.

What was studied?

This study looked at how the oral microbiome (the bacteria in the mouth) is affected by human papillomavirus (HPV) infection, especially in people with and without HIV. Researchers analyzed mouth rinse samples from 63 men, comparing their bacterial composition based on whether they had HPV and/or HIV. They found that HPV infection changes the diversity and types of bacteria in the mouth, but these changes were different depending on whether the person also had HIV. In HIV-negative individuals, certain bacteria were more common when HPV was present, while in HIV-positive individuals, different bacterial shifts were observed. The study suggests that HPV infection interacts with the oral microbiome in unique ways, and this interaction may be influenced by HIV status.