Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Gut microbiota changes in preeclampsia, abnormal placental growth and healthy pregnant women.

BACKGROUND: Preeclampsia (PE) is a condition of high blood pressure that is usually concurrent with proteinuria in pregnancy. PE complicates the management of both maternal and fetal health and contributes to most adverse pregnancy outcomes, but the mechanism underlying the development of PE remains unclear. In this study, we performed a case-control study to compare the gut microbiota of PE (n = 26), abnormal placental growth (APG, n = 25) and healthy pregnant women (n = 28) and analyzed the potential pathogenic role of gut microbiota in PE progression. RESULTS: The clinical pathophysiological state did not affect the bacterial diversity, while the compositions of the gut microbiota were significantly altered in both the PE and APG groups compared with healthy pregnant women. At the phylum level, TM7 was significantly increased in women with APG. Heterogeneity was observed at the genus level, especially in genera with positive LDA scores, suggesting the stage-dependent effect of gut microbiota on the development of PE. The beneficial bacterium Lactobacillus was markedly depleted in the PE and APG groups but was only correlated with blood pressure (BP) and proteinuria levels in the PE group. Two different bacterial taxa belonged to Lactobacillus showed different correlations (OTU255 and OTU784 were significantly related to PE and APG, respectively). CONCLUSIONS: Our results indicated that shifts in the gut microbiota might occur from the early stages of the development of PE, which is of possible etiological and therapeutic importance.

Role of Periodontal Bacteria, Viruses, and Placental mir155 in Chronic Periodontitis and Preeclampsia-A Genetic Microbiological Study.

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with mir155 levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18-35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as Tf, Td, Pg, Pi, Fn, HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, Tf, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and mir 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and mir 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, mir155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. mir155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.

Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing.

OBJECTIVES: Preeclampsia is a dangerous pregnancy complication. The source of preeclampsia is unknown, though the placenta is believed to have a central role in its pathogenesis. An association between maternal infection and preeclampsia has been demonstrated, yet the involvement of the placental microbiome in the etiology of preeclampsia has not been determined. In this study, we examined whether preeclampsia is associated with an imbalanced microorganism composition in the placenta. METHODS: To this end, we developed a novel method for the identification of bacteria/viruses based on sequencing of small non-coding RNA, which increases the microorganism-to-host ratio, this being a major challenge in microbiome methods. We validated the method on various infected tissues and demonstrated its efficiency in detecting microorganisms in samples with extremely low bacterial/viral biomass. We then applied the method to placenta specimens from preeclamptic and healthy pregnancies. Since the placenta is a remarkably large and heterogeneous organ, we explored the bacterial and viral RNA at each of 15 distinct locations. RESULTS: Bacterial RNA was detected at all locations and was consistent with previous studies of the placental microbiome, though without significant differences between the preeclampsia and control groups. Nevertheless, the bacterial RNA composition differed significantly between various areas of the placenta. Viral RNA was detected in extremely low quantities, below the threshold of significance, thus viral abundance could not be determined. CONCLUSIONS: Our results suggest that the bacterial and viral abundance in the placenta may have only limited involvement in the pathogenesis of preeclampsia. The evidence of a heterogenic bacterial RNA composition in the various placental locations warrants further investigation to capture the true nature of the placental microbiome.

Pregnant women who develop preeclampsia have lower abundance of the butyrate-producer Coprococcus in their gut microbiota.

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and dysfunction of several organs, that is associated with maternal and fetal complications. The human gut microbiota is related to health and disease including hypertension. Alterations in gut microbiota composition can change the short-chain fatty acid profile released by the bacteria and contribute to hypertension and metabolic syndrome. It is unclear if the composition of the gut microbiota is altered in women who develop late-onset preeclampsia. In this study, we investigated the composition of the gut microbiota at 28 weeks gestation in women who developed late-onset (>34 weeks gestation) preeclampsia (DPE) by 16S rRNA gene amplicon sequencing of fecal samples obtained from 213 pregnant women in the SPRING cohort (Study of Probiotics IN Gestational diabetes). Quantitative real-time PCR was used to assess the density of butyrate-producing genes. Gut microbiota composition was compared between women with and without DPE. The abundance of the butyrate-producing Coprococcus genus significantly decreased in DPE. Abundance of Coprococcus is significantly and positively correlated with the abundance of genes encoding the terminal step in bacterial butyrate formation (but and buk). Women with DPE also had significantly reduced levels of serum butyrate prior to the development of symptoms than controls. This study suggests that a reduction in the abundance of butyrate-producing bacteria, and Coprococcus spp. in particular, may contribute to an increased risk of developing preeclampsia in pregnant women.

A joint modeling approach for longitudinal microbiome data improves ability to detect microbiome associations with disease.

Changes in the composition of the microbiome over time are associated with myriad human illnesses. Unfortunately, the lack of analytic techniques has hindered researchers' ability to quantify the association between longitudinal microbial composition and time-to-event outcomes. Prior methodological work developed the joint model for longitudinal and time-to-event data to incorporate time-dependent biomarker covariates into the hazard regression approach to disease outcomes. The original implementation of this joint modeling approach employed a linear mixed effects model to represent the time-dependent covariates. However, when the distribution of the time-dependent covariate is non-Gaussian, as is the case with microbial abundances, researchers require different statistical methodology. We present a joint modeling framework that uses a negative binomial mixed effects model to determine longitudinal taxon abundances. We incorporate these modeled microbial abundances into a hazard function with a parameterization that not only accounts for the proportional nature of microbiome data, but also generates biologically interpretable results. Herein we demonstrate the performance improvements of our approach over existing alternatives via simulation as well as a previously published longitudinal dataset studying the microbiome during pregnancy. The results demonstrate that our joint modeling framework for longitudinal microbiome count data provides a powerful methodology to uncover associations between changes in microbial abundances over time and the onset of disease. This method offers the potential to equip researchers with a deeper understanding of the associations between longitudinal microbial composition changes and disease outcomes. This new approach could potentially lead to new diagnostic biomarkers or inform clinical interventions to help prevent or treat disease.

Changes in intestinal flora in preeclampsia rats and effects of probiotics on their inflammation and blood pressure.

OBJECTIVE: The aim of this study was to investigate the changes in intestinal flora in preeclampsia rats and the effects of probiotics on their inflammation and blood pressure. MATERIALS AND METHODS: A total of 40 Specific Pathogen Free (SPF) Wistar rats were randomly selected in this study. Abdominal operation was performed to reduce uterine blood perfusion, so as to establish the model of preeclampsia in rats. All rats were randomly divided into two groups, namely, observation group (treated with probiotics, n=20) and control group (not treated with probiotics, n=20). Subsequently, the changes in serum endotoxin level during intervention, the 24-h urinary 99mTc-diethylene triamine pentaacetic acid (DTPA) excretion rate, and intestinal flora colonization ability after intervention were compared between the two groups. The distribution of intestinal flora after intervention was recorded in the two groups. Meanwhile, vascular endothelial function and blood pressure following intervention were compared between the two groups as well. In addition, the changing trend of inflammatory cytokines during intervention in the two groups, and the correlation of colonization ability of intestinal flora with changes in systolic blood pressure and high-sensitivity C-reactive protein (hs-CRP) level in patients were analyzed. RESULTS: At 3 days and 1 week after intervention, serum endotoxin level in the observation group was significantly lower than that in the control group at the same period (p<0.05). Following intervention, observation group exhibited remarkably higher excretion rate of 24-h urinary 99mTc-DTPA (p<0.05), stronger colonization ability of intestinal flora (p<0.05), higher levels of Bifidobacteria and Lactobacillus in intestinal flora (p<0.05), lower level of endothelin-1 (ET-1) (p<0.05) and higher level of nitric oxide (NO) (p<0.05) than the control group. In addition, the systolic blood pressure and diastolic blood pressure in the observation group were basically normal, which were both notably lower than those in the control group (p<0.05). At 3 days and 1 week after intervention, the levels of serum inflammatory cytokine hs-CRP in the observation group was markedly lower than that in the control group (p<0.05) at the same period. Furthermore, the colonization ability of intestinal flora was negatively associated with the changes in systolic blood pressure and hs-CRP level in patients (p<0.05). CONCLUSIONS: Treating preeclampsia rats with probiotics can effectively reduce the level of serum endotoxin, improve the body's capacity to eliminate metabolites and the colonization ability of intestinal flora, maintain the stability of intestinal flora, enhance vascular endothelial function, and reduce blood pressure and the body's inflammatory responses.

Determination of the Role of Fusobacterium Nucleatum in the Pathogenesis in and Out the Mouth.

INTRODUCTION: One of the most important types of microorganisms in the oral cavity in both healthy and non-healthy individuals is Fusobacterium nucleatum. Although present as a normal resident in the oral cavity, this Gram-negative pathogen is dominant in periodontal disease and it is involved in many invasive infections in the population, acute and chronic inflammatory conditions, as well as many adverse events with a fatal outcome. AIM: To determine the role of F. nucleatum in the development of polymicrobial biofilms thus pathogenic changes in and out of the oral media. MATERIAL AND METHOD: A systematic review of the literature concerning the determination and role of F. nucleatum through available clinical trials, literature reviews, original research and articles published electronically at Pub Med and Google Scholar. CONCLUSION: The presence of Fusobacterium nucleatum is commonly associated with the health status of individuals. These anaerobic bacteria plays a key role in oral pathological conditions and has been detected in many systemic disorders causing complex pathogenethic changes probably due to binding ability to various cells thus several virulence mechanisms. Most common diseases and conditions in the oral cavity associated with F.nucleatum are gingivitis (G), chronic periodontitis (CH), aggressive periodontitis (AgP), endo-periodental infections (E-P), chronic apical periodontitis (PCHA). The bacterium has been identified and detected in many systemic disorders such as coronary heart disease (CVD) pathological pregnancy (P); polycystic ovary syndrome (PCOS), high-risk pregnancy (HRP), colorectal cancer (CRC); pre-eclampsia (PE); rheumatoid arthritis (RA); osteoarthritis (OA).

Pre-Eclampsia: Microbiota possibly playing a role.

Pre-eclampsia (PE) is a complication of pregnancy that is associated with mortality and morbidity in mothers and fetuses worldwide. Oxygen dysregulation in the placenta, abnormal remodeling of the spiral artery, defective placentation, oxidative stress at the fetal-maternal border, inflammation and angiogenic impairment in the maternal circulation are the main causes of this syndrome. These events result in a systemic and diffuse endothelial cell dysfunction, an essential pathophysiological feature of PE. The impact of bacteria on the multifactorial pathway of PE is the recent focus of scientific inquiry since microbes may cause each of the aforementioned features. Microbes and their derivatives by producing antigens and other inflammatory factors may trigger infection and inflammatory responses. A mother's bacterial communities in the oral cavity, gut, vagina, cervix and uterine along with the placenta and amniotic fluid microbiota may be involved in the development of PE. Here, we review the mechanistic and pathogenic role of bacteria in the development of PE. Then, we highlight the impact of alterations in a set of maternal microbiota (dysbiosis) on the pathogenesis of PE.

Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia.

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation.

OBJECTIVE: Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown. DESIGN: We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation. RESULTS: Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased. CONCLUSIONS: This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

Maternal microbiome and the hypertensive disorder of pregnancy, preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder that can be life threatening for both mother and baby. It is characterized by a new onset hypertension during the second half of pregnancy and affects ~300,000 women in the United States every year. There is no cure for PE, and the only effective treatment is delivery of the placenta and the fetus, which is often preterm. PE is believed to be a severe manifestation of placental dysfunction due to early angiogenic imbalances and inflammatory disturbances; however, the cause of this is unknown. The once thought "sterile" placenta now has been proposed to have a unique microbiome of its own. Under ideal conditions, the microbiome represents a balanced bacterial community that is important to the maintenance of a healthy environment. Dysbiosis of these communities may lead to inflammation that potentially contributes to adverse pregnancy outcomes, such as preterm birth and PE. Thus far, the female reproductive tract microbiome has been found to be influenced by periodontal disease, cardiometabolic complications, and maternal obesity, all of which have been identified as contributors to PE. This review will look at the maternal reproductive tract microbiome, evidence for and against, and its role in pregnancy and PE-related events as well as data from relevant mouse models that could be useful for further investigating the influence of the reproductive tract microbiome on the pathogenesis of PE.

Urinary Tract Infections and Preeclampsia among Pregnant Women Attending Two Hospitals in Mwanza City, Tanzania: A 1:2 Matched Case-Control Study.

Urinary tract infection (UTI) and preeclampsia are common among pregnant women and are associated with adverse maternal-fetal and neonatal outcomes. Despite this, limited information exists on the association between UTIs and preeclampsia in Tanzania to guide specific management and thereby averting the adverse outcomes. A 1:2 matched case-control study (by age and gravidity) involving 131 pregnant women with preeclampsia (cases) and 262 without preeclampsia (controls) was conducted. Sociodemographic and clinical information was collected using a questionnaire. Midstream urine samples were collected during admission for culture and antimicrobial susceptibility testing (AST). Out of 393 pregnant women enrolled, 110 (28.0%), 95% CI: 23.8%-32.7%, had significant bacteriuria [cases: 50.4% (66/131) and control: 16.8% (44/262)]. Pregnant women with preeclampsia had 7.7 odds of having significant bacteriuria than those without preeclampsia [OR=7.7, 95% CI (4.11-14.49); p-value <0.001]. Escherichia coli, 50 (45.5%), and Klebsiella spp., 25 (23.6%), predominated, and resistance to gentamicin, ceftriaxone, and piperacillin-tazobactam ranged from 9.0% to 29.0% in these dominant species. Extended spectrum beta lactamases (ESBL) production in Escherichia coli and Klebsiella spp. was 18.0% (9/50) and 15.4% (4/26), respectively. Routine urine culture and AST among pregnant women with preeclampsia should be introduced in the antenatal clinics to ensure prompt management. Delineation of maternal-fetal and neonatal outcomes among pregnant women with preeclampsia and UTIs would be of interest in future studies.

Through the Microbial Looking Glass: Premature Labor, Preeclampsia, and Gestational Diabetes: A Scoping Review.

The influence of microbial factors on adverse perinatal outcomes has become the focal point of recent investigations, with particular interest in the role of the microbiome and probiotic interventions. The purpose of this scoping review was to identify and critique the most recent evidence about these factors as they relate to pregnancies complicated by preeclampsia (PEC), preterm birth (PTB), and gestational diabetes mellitus (GDM). Four databases (PubMed, EMBASE, Web of Science, and Cochrane) were searched for articles published in English in the last 10 years with the concepts of the microbiome, probiotics, and PEC, PTB, or GDM. Forty-nine articles were eligible for full-text review. Five articles were excluded, leaving 44 articles that met all the eligibility criteria. The relationships between the microbiome and the risk for PEC, PTB, and GDM are not fully elucidated, although probiotic interventions seem beneficial in decreasing PEC and GDM risk. Probiotic interventions targeting bacterial vaginosis and elimination of infection in women at risk for PTB appear to be beneficial. More research is needed to understand the contributions of the microbiome to adverse perinatal outcomes. Probiotic interventions appear to be effective in reducing risk for select outcomes.

Prenatal complications are associated with the postnatal airway host response and microbiota in intubated preterm infants.

PURPOSE: To prospectively examine the relationship between prenatal events, postnatal airway host response and microbiota, and clinical outcomes. MATERIALS AND METHODS: Tracheal aspirates collected at seven days of age from 71 mechanically ventilated infants (median gestational age (GA), 25 weeks [range 23-28]) were simultaneously processed for a 12-plex protein assay and bacterial identification by 16S rRNA sequencing. Phenotypes were determined by unsupervised clustering of the protein analytes. Subject characteristics, microbial communities and clinical factors and outcomes were compared across the phenotype groups. RESULTS: Three clusters were identified: 1 (high protein levels), 2 (high proinflammatory proteins and low anti-inflammatory proteins), and 3 (low protein levels), respectively. Antenatal hemorrhage was most common in cluster 1, while chorioamnionitis characterized cluster 2 and preeclampsia was most prevalent in cluster 3, which was characterized by a predominance of Staphylococcus and relative absence of Ureaplasma. There were higher rates of adverse clinical outcomes in cluster 1. CONCLUSIONS: Airway protein profiles in seven days old mechanically ventilated preterm infants are associated with important antenatal events and unique airway microbial communities. These relationships may reveal new mechanisms by which antenatal events impact the course and outcomes of preterm infants.

Characteristics and pregnancy outcomes of patients with severe pneumonia complicating pregnancy: a retrospective study of 12 cases and a literature review.

BACKGROUND: Pneumonia during pregnancy has been proven to be associated with increased maternal and fetal morbidity and mortality. The management of severe pneumonia in gravid patients is even more challenging. Thus, we summarized the characteristics and pregnancy outcomes of these patients and explored the probable risk factors and predictive factors for pneumonia during pregnancy and the appropriate timing of delivery in severe pneumonia patients. METHODS: A retrospective cohort study was conducted with 12 patients who were diagnosed with severe pneumonia complicating pregnancy at Peking Union Medical College Hospital between January 2010 and June 2017. The clinical features, treatment strategies, and pregnancy outcomes were collected from medical records and telephone calls. RESULTS: All 12 patients were in their late second or third trimester. The patients had a higher prevalence of anemia (50%) and preeclampsia (25%) than ordinary pregnant women. Delayed diagnoses were not uncommon. Two mothers died in our series, resulting in a mortality rate of 17%. Two intrauterine deaths were observed. Elective delivery was not performed in any of the four patients in their second trimester. Six of the seven patients who presented after 28 weeks of gestation and had live fetuses underwent emergency deliveries. Preterm births (6/7) and cesarean sections (5/7) were the two leading adverse outcomes in newborns. CONCLUSIONS: Anemia, advanced gestational age, and preeclampsia might be associated with the severity of pneumonia. Chest radiographs should be taken as soon as pneumonia is highly suspected to facilitate an early diagnosis. High incidences of adverse fetal outcomes were observed; thus, termination of the pregnancy is recommended for patients in their third trimester when respiratory function deteriorates progressively. However, it might be reasonable to continue pregnancy for those in their first or second trimester.

Association between specific periodontal pathogens, Toll-like receptor-4, and nuclear factor-κB expression in placental tissues of pre-eclamptic women with periodontitis.

AIM: The aim of the present study was to determine the association between the presence of specific periodontal pathogens, Toll-like receptor-4 (TLR-4), and nuclear factor-κB (NF-κB) expression in the placental tissues of pre-eclamptic women. METHODS: Antenatal periodontal screening was performed in 25 normotensive pregnant women and 25 pre-eclamptic women. Subgingival plaque and placental tissue samples were collected from both groups and screened for the presence of Porphyromonas gingivalis (P. gingivalis), Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia (P. intermedia) using real-time polymerase chain reaction. The placental samples were also analyzed to quantify TLR-4 and NF-κB expression. RESULTS: The subgingival plaque samples of pre-eclamptic women showed significantly higher frequencies of P. intermedia. In the placental samples, P. gingivalis, P. intermedia, and the expression of TLR-4 and NF-κB were found to be at significantly higher levels compared to normotensive pregnant women. Using linear regression analysis, the expression of TLR-4 was significantly influenced by the presence of P. gingivalis (coefficient=3.176, 95% confidence interval [CI]: 367-5.986) and P. intermedia (coefficient=2.886, 95% CI: 0.77-5.696), whereas NF-κB expression was influenced only by the presence of P. intermedia (coefficient=2.220, 95% CI: 0.051-4.388) in the placental tissues of pre-eclamptic women. CONCLUSION: An association exists between P. gingivalis and P. intermedia with increased TLR-4 and NF-κB expression in the placenta of pre-eclamptic women with periodontitis.

Human infectious diseases and risk of preeclampsia: an updated review of the literature.

BACKGROUND: Preeclampsia (PE) is one of the major causes of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries. In recent years, a growing body of literatures suggests that infections by bacteria, viruses, and parasites and their related inflammations play an important role in the pathogenesis of PE. METHODS: We searched PubMed, Google scholar, and Cochrane databases using the following search words: "infection and preeclampsia," "bacterial infection and preeclampsia," "viral infection and preeclampsia" and "parasitic infection and preeclampsia." RESULTS: The literature review revealed that many bacteria including Helicobacter pylori, Chlamydia pneumonia, and those are involved in periodontal disease or urinary tract infections (UTIs) and some viral agents such as Cytomegalovirus, herpes simplex virus type-2, human immunodeficiency virus, and some parasites especially Plasmodium spp. and Toxoplasma gondii can be effective in development of PE. Inflammation responses against infections has major role in the inducement of PE. The shift of immunological cytokine profile of Th2 toward Th1 and high levels of pro-inflammatory cytokines (TNF-ɑ, IL-12, IFN-γ, etc.), increase of oxidative stress, increase of anti-angiogenic proteins, increase of vascular endothelial growth factor receptor 1 (sVEGFR1), and complement C5a are the main potential mechanisms related to infections and enhanced development of PE. CONCLUSION: Thus, early diagnosis and treatment of bacterial, viral, and parasitic infections could be an effective strategy to reduce the incidence of PE.