Role of the vaginal microbiome in miscarriage: exploring the relationship.

Miscarriage is a devastating pregnancy loss that affects many women worldwide. It is characterized as a spontaneous miscarriage that occurs before 20 weeks of gestation which affects more than 25% of pregnancies. While the causes of miscarriage are complex and multifactorial, recent research has suggested a potential role of the vaginal microbiota. The vaginal microbiome is a dynamic ecosystem of microbes that are essential for preserving vaginal health and avoiding infections. Vaginal dysbiosis has been accompanied with numerous adverse pregnancy complications, such as preterm birth. However, the effect of the vaginal microbiome in miscarriage is not fully understood. This review aims to investigate the link between vaginal microbiota and miscarriage. Also, we investigate the various mechanisms through which the vaginal microbiota may affect miscarriage. Additionally, we examine the implications of these research findings, specifically the possibility of vaginal microbiome screening and targeted interventions to prevent miscarriage.

Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, ß7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.

Infections and Pregnancy: Effects on Maternal and Child Health.

Pregnancy causes physiological and immunological adaptations that allow the mother and fetus to communicate with precision in order to promote a healthy pregnancy. At the same time, these adaptations may make pregnant women more susceptible to infections, resulting in a variety of pregnancy complications; those pathogens may also be vertically transmitted to the fetus, resulting in adverse pregnancy outcomes. Even though the placenta has developed a robust microbial defense to restrict vertical microbial transmission, certain microbial pathogens have evolved mechanisms to avoid the placental barrier and cause congenital diseases. Recent mechanistic studies have begun to uncover the striking role of the maternal microbiota in pregnancy outcomes. In this review, we discuss how microbial pathogens overcome the placental barrier to cause congenital diseases. A better understanding of the placental control of fetal infection should provide new insights into future translational research.

Tipping the Balance: Vitamin D Inadequacy in Children Impacts the Major Gut Bacterial Phyla.

Vitamin D inadequacy appears to be on the rise globally, and it has been linked to an increased risk of osteoporosis, as well as metabolic, cardiovascular, and autoimmune diseases. Vitamin D concentrations are partially determined by genetic factors. Specific single nucleotide polymorphisms (SNPs) in genes involved in vitamin D transport, metabolism, or binding have been found to be associated with its serum concentration, and these SNPs differ among ethnicities. Vitamin D has also been suggested to be a regulator of the gut microbiota and vitamin D deficiency as the possible cause of gut microbial dysbiosis and inflammation. This pilot study aims to fill the gap in our understanding of the prevalence, cause, and implications of vitamin D inadequacy in a pediatric population residing in Qatar. Blood and fecal samples were collected from healthy subjects aged 4-14 years. Blood was used to measure serum metabolite of vitamin D, 25-hydroxycholecalciferol 25(OH)D. To evaluate the composition of the gut microbiota, fecal samples were subjected to 16S rRNA gene sequencing. High levels of vitamin D deficiency/insufficiency were observed in our cohort with 97% of the subjects falling into the inadequate category (with serum 25(OH)D < 75 nmol/L). The CT genotype in rs12512631, an SNP in the GC gene, was associated with low serum levels of vitamin D (ANOVA, p = 0.0356) and was abundant in deficient compared to non-deficient subjects. Overall gut microbial community structure was significantly different between the deficient (D) and non-deficient (ND) groups (Bray Curtis dissimilarity p = 0.049), with deficient subjects also displaying reduced gut microbial diversity. Significant differences were observed among the two major gut phyla, Firmicutes (F) and Bacteroidetes (B), where deficient subjects displayed a higher B/F ratio (p = 0.0097) compared to ND. Vitamin D deficient children also demonstrated gut enterotypes dominated by the genus Prevotella as opposed to Bacteroides. Our findings suggest that pediatric vitamin D inadequacy significantly impacts the gut microbiota. We also highlight the importance of considering host genetics and baseline gut microbiome composition in interpreting the clinical outcomes related to vitamin D deficiency as well as designing better personalized strategies for therapeutic interventions.

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar.

BACKGROUND: Pregnancy is governed by multiple molecular and cellular processes, which might influence pregnancy health and outcomes. Failure to predict and understand the cause of pregnancy complications, adverse pregnancy outcomes, infant's morbidity and mortality, have limited effective interventions. Integrative multi-omics technologies provide an unbiased platform to explore the complex molecular interactions with an unprecedented depth. The objective of the present protocol is to build a longitudinal mother-baby cohort and use multi-omics technologies to help identify predictive biomarkers of adverse pregnancy outcomes, early life determinants and their effect on child health. METHODS/DESIGN: One thousand pregnant women with a viable pregnancy in the first trimester (6-14 weeks of gestation) will be recruited from Sidra Medicine hospital. All the study participants will be monitored every trimester, at delivery, and one-year post-partum. Serial high-frequency sampling, including blood, stool, urine, saliva, skin, and vaginal swabs (mother only) from the pregnant women and their babies, will be collected. Maternal and neonatal health, including mental health and perinatal growth, will be recorded using a combination of questionnaires, interviews, and medical records. Downstream sample processing including microbial profiling, vaginal immune response, blood transcriptomics, epigenomics, and metabolomics will be performed. DISCUSSION: It is expected that the present study will provide valuable insights into predicting pregnancy complications and neonatal health outcomes. Those include whether specific microbial and/or epigenomics signatures, immune profiles are associated with a healthy pregnancy and/or complicated pregnancy and poor neonatal health outcome. Moreover, this non-interventional cohort will also serve as a baseline dataset to understand how familial, socioeconomic, environmental and lifestyle factors interact with genetic determinants to influence health outcomes later in life. These findings will hold promise for the diagnosis and precision-medicine interventions.

COVID-19 Infection during Pregnancy: Risk of Vertical Transmission, Fetal, and Neonatal Outcomes.

The COVID-19 pandemic is a worldwide, critical public health challenge and is considered one of the most communicable diseases that the world had faced so far. Response and symptoms associated with COVID-19 vary between the different cases recorded, but it is amply described that symptoms become more aggressive in subjects with a weaker immune system. This includes older subjects, patients with chronic diseases, patients with immunosuppression treatment, and pregnant women. Pregnant women are receiving more attention not only because of their altered physiological and immunological function but also for the potential risk of viral vertical transmission to the fetus or infant. However, very limited data about the impact of maternal infection during pregnancy, such as the possibility of vertical transmission in utero, during birth, or via breastfeeding, is available. Moreover, the impact of infection on the newborn in the short and long term remains poorly understood. Therefore, it is vital to collect and analyze data from pregnant women infected with COVID-19 to understand the viral pathophysiology during pregnancy and its effects on the offspring. In this article, we review the current knowledge about pre-and post-natal COVID-19 infection, and we discuss whether vertical transmission takes place in pregnant women infected with the virus and what are the current recommendations that pregnant women should follow in order to be protected from the virus.

Vaginal Microbiota and Cytokine Levels Predict Preterm Delivery in Asian Women.

Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs is linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to longitudinally analyzed the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis, and lower levels of Lactobacillus crispatus and Finegoldia, accompanied by decreased levels of cytokines including IFNγ, IL-4, and TNFα. Differences in the vaginal microbial diversity and local vaginal immune environment were associated with greater risk of preterm birth. Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.

Oral microbiome and pregnancy: A bidirectional relationship.

The oral cavity contains the second most complex microbial population within the human body, with more than 700 bacterial organisms. Recent advances in Next Generation Sequencing technology have unraveled the complexities of the oral microbiome and provided valuable insights into its role in health and disease. The human oral microbiome varies dramatically during the different stages of life, including pregnancy. The total viable microbial counts in pregnant women are known to be higher compared to non-pregnant women, especially in the first trimester of pregnancy. A balanced oral microbiome is vital for a healthy pregnancy, as perturbations in the oral microbiome composition can contribute to pregnancy complications. On the other hand, physiological changes and differences in hormonal levels during pregnancy, increase susceptibility to various oral diseases such as gingivitis and periodontitis. A growing body of evidence supports the link between the composition of the oral microbiome and adverse pregnancy outcomes such as preterm birth, preeclampsia, low birth weight among others. This review aims to summarize the dynamics of oral microbiome during pregnancy and to discuss the relationship between a dysbiotic oral microbiome and pregnancy complications.

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data.

According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observed in vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules-phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage.

Profiling the Salivary microbiome of the Qatari population.

BACKGROUND: The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions. MATERIALS AND METHODS: We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1-V3 region of the 16S rRNA gene. RESULTS: In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers. CONCLUSION: This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.

Histopathological effects and determination of the putative receptor of Bacillus thuringiensis Cry1Da toxin in Spodoptera littoralis midgut.

Bacillus thuringiensis subsp. aizawai strain HD133, known by its effectiveness against Spodoptera species, produces many insecticidal proteins including Cry1Ab, Cry1Ca and Cry1Da. In the present study, the insecticidal activity of Cry1Da against Spodoptera littoralis was investigated. It showed toxicity with an LC(50) of 224.4 ng/cm(2) with 95% confidence limits of (178.61-270.19) and an LC(90) of 467.77 ng/cm(2) with 95% confidence limits of (392.89-542.65). The midgut histopathology of Cry1Da fed larvae showed vesicle formation in the apical region, vacuolization and destruction of epithelial cells. Biotinylated-activated Cry1Da toxin bound protein of about 65 kDa on blots of S. littoralis brush border membrane preparations. This putative receptor differs in molecular size from those recognized by Cry1C and Vip3A which are active against this polyphagous insect. This difference in midgut receptors strongly supports the use of Cry1Da as insecticidal agent, particularly in case of Cry and/or Vip-resistance management.