Broadening horizons: intestinal microbiota as a novel biomarker and potential treatment for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.

Human milk microbiota development during lactation and its relation to maternal geographic location and gestational hypertensive status.

Bacteria in human milk could directly seed the infant intestinal microbiota, while information about how milk microbiota develops during lactation and how geographic location, gestational hypertensive status, and maternal age influence this process is limited. Here, we collected human milk samples from mothers of term infants at the first day, 2 weeks, and 6 weeks postpartum from 117 longitudinally followed-up mothers (age: 28.7 ± 3.6 y) recruited from three cities in China. We found that milk microbial diversity and richness were the highest in colostrum but gradually decreased over lactation. Microbial composition changed across lactation and exhibited more discrete compositional patterns in 2-week and 6-week milk samples compared with colostrum samples. At phylum level, the abundance of Proteobacteria increased during lactation, while Firmicutes showed the opposite trend. At genus level, Staphylococcus, Streptococcus, Acinetobacter, Pseudomonas, and Lactobacillus were predominant in colostrum samples and showed distinct variations across lactation. Maternal geographic location was significantly associated with the milk microbiota development and the abundance of predominant genus. In addition, milk from mothers with gestational prehypertension had a different and less diverse microbial community at genus level in early lactation times, and contained less Lactobacillus in the 2-week milk samples than those from normotensive mothers. Findings of our study outlined the human milk microbial diversity and community development over lactation, and underscored the importance of maternal geographic locations and gestational hypertensive status on milk microbiota, which might have important implications in the establishment of the infant intestinal microbiota via breastfeeding.

A pregnancy complication-dependent change in SIgA-targeted microbiota during third trimester.

Gut microbiota play a crucial role in metabolic dysfunction during gestation, which might be prevented by using probiotics. This study compared the composition of the gut microbiota in healthy and complicated pregnancies, for screening and isolating healthy pregnancy-derived probiotics. According to the principal component analysis of secretory immunoglobulin A (SIgA)-coated microbiota in the gut, third-trimester volunteers can be divided into three groups: AHd (n = 29), GDMd (n = 37), and GHd (n = 25), dominated by asymptomatic healthy donors (62.07%), gestational diabetes mellitus (GDM) donors (40.54%), and gestational hypertension (GH) donors (40%), respectively. There was a significant difference in ß-diversity (p < 0.01) and α-diversity (p < 0.05) among the three groups. At the phylum level, the Firmicutes of the GHd group were significantly lower than those of the AHd group (p = 0.039), while Bacteroidetes (p = 0.005) and Proteobacteria (p = 0.002) of the GHd group were more dominant than those of the AHd group. At the genus level, the linear discriminant analysis effect size showed that SIgA-targeted Enterococcus was the dominant taxonomic biomarker of the AHd group, and the GHd group was enriched with Escherichia and Streptococcus. The GDMd and GHd groups had higher faecal calprotectin, serum lipopolysaccharide, zonulin, and GLYCAM-1 levels. We conclude that the occurrence of complications in the third trimester may be related to intestinal barrier injury associated with disorders of the intestinal SIgA-targeted microbiota; gut barrier injury triggers inflammation in pregnant women. SIgA-targeted L. reuteri showed a significant correlation with low inflammatory response and may be a potential probiotic candidate for preventing pregnancy complications.

Porphyromonas gingivalis, Treponema denticola and toll-like receptor 2 are associated with hypertensive disorders in placental tissue: a case-control study.

AIM(S): To explore the associations between the presence of periodontal pathogens and the expression of toll-like receptors (TLR-2 and TLR-4) in the placental tissue of patients with hypertensive disorders compared to the placentas of healthy normotensive patients. MATERIAL AND METHODS: A case-control study was performed. From a cohort composed of 126 pregnant women, 33 normotensive healthy pregnant women were randomly selected, and 25 cases of patients with hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, were selected. Placental biopsy was obtained after aseptic placental collection at the time of delivery. All of the samples were processed and analysed for the detection of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia using the polymerase chain reaction (PCR) technique. Determination of the expressions of TLR-2 and TLR-4 was performed in samples of total purified protein isolated from placental tissues and analysed by ELISA. The data were assessed using descriptive statistics. The associations among variables were estimated through multiple logistic regression models and the Mann-Whitney test to evaluate the differences between the two groups. RESULTS: A significant increase was observed in the expression of TLR-2 in the placentas of patients with hypertensive disorders (p = 0.04). Additionally, the multiple logistic regression models demonstrated an association between the presence of T. denticola and P. gingivalis in placental tissues and hypertensive disorders (OR: 9.39, p = 0.001, CI 95% 2.39-36.88 and OR: 7.59, p = 0.019, CI 95% 1.39-41.51, respectively). CONCLUSIONS: In the present study, pregnant women with periodontal disease presented an association in the placental tissue between the presence of T. denticola and P. gingivalis and hypertensive disorders. Additionally, increased expression of TLR-2 was observed. However, further studies are required to determine the specific roles of periodontal pathogens and TLRs in the placental tissue of patients with pregnancy-related hypertensive disorders.

Leptospirosis in pregnancy.

Leptospirosis is a direct zoonotic disease caused by spirochetes belonging to the genus Leptospira. Many animals act as carriers or vectors. Human infection results from accidental contact with carrier animals or environment contaminated with animal urine containing the organism. Epidemics of leptospirosis result from poor sanitation in urban areas and are aggravated following natural calamities. The majority of leptospiral infections are either subclinical or result in very mild illness and patients recover without complications. In a few cases it may manifest as multiorgan failure where the mortality can go up to 40%. Infection in pregnant women may be grave leading to severe fetal and maternal morbidity and mortality. The presentation may mimic other viral, bacterial, and parasitic infections, acute fatty liver, pregnancy-induced hypertension, and HELLP syndrome. Owing to the unusual presentation, leptospirosis in pregnancy is often misdiagnosed and under-reported. Preventive public education regarding hygiene, personal practices, source reduction, environmental sanitation, early diagnosis, and treatment of the condition are needed to avoid perinatal and maternal mortality.

Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy.

BACKGROUND: There are many studies documenting increased prevalence of periodontal infection in women with preeclampsia. But, very few studies have attempted to establish causal relationship between the two. OBJECTIVE: To find out causal circumstantial evidence by isolating specific periodontal pathogens in oral and placental samples. MATERIALS AND METHODS: Antenatal periodontal screening and subgingival plaque collection was carried out in ten women with hypertension in pregnancy and ten normotensive controls on their hospital admission at term for cesarean delivery. Placental biopsy was obtained after aseptic placental collection at the time of elective cesarean delivery. Subgingival plaque and placental biopsy were studied for Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans using quantitative polymerase chain reaction technique. Periodontist and laboratory personnel were unaware of case or control status. Periodontal status was not informed to the obstetrician recruiting the cases and laboratory. Microbiology report was not revealed till end of the study. RESULTS: Periodontal pathogens were found to be high in the group with hypertension than the controls. P gingivalis was found in all the samples from subgingival plaque and placenta, irrespective of the periodontal disease status. CONCLUSION: In cases with hypertension, periodontal pathogens are present in higher proportion in subgingival plaque and placenta.

Risk of pregnancy-related hypertension within five years of exposure to bacteria-contaminated drinking water.

Exposure to Escherichia coli O157:H7 may result in subclinical kidney injury manifesting as hypertension during pregnancy. We evaluated the risk of pregnancy-related hypertension (PRH) among previously healthy females from the Walkerton Health Study, Canada (2002-6), who conceived within five years of exposure to bacteria-contaminated drinking water. Ontario Ministry of Health Antenatal forms were used to determine outcomes and risk factors. PRH was defined as any systolic or diastolic blood pressure (BP) > or =140 mm Hg and > or =90 mm Hg, respectively. Chronic and gestational hypertension were defined, respectively, as elevated BP observed prior to or at > or =20 weeks gestation. Risk of PRH was evaluated using a modified Poisson regression model that controlled for known risk factors. Of 148 eligible pregnancies, antenatal audits with blood pressure data were available for 135. PRH was detected in 20.7% pregnancies, of which 6.7% were chronic hypertension and 14.1% gestational hypertension. Although nonsignificant, we observed a consistent trend toward higher rates of PRH and mean arterial pressure, particularly prior to 20 weeks gestation, among women who reported symptomatic gastroenteritis compared to asymptomatic women. BP should be monitored closely in women after exposure to contaminated water.

Prevalence of asymptomatic bacteriuria and its consequences in pregnancy in a rural community of Bangladesh.

This was a cross-sectional followed by cohort type of study conducted among the pregnant mothers of second trimester in the rural areas of Rajshahi district. Initially 1800 pregnant mothers ofsecond trimester were selected from 18 unions applying 2-stage random sampling. A total of 216 pregnant mothers with asymptomatic bacteriuria were paired among the rest of the healthy pregnant mothers (without bacteriuria) on the basis of age, gravida and economic status for cohort study to relate asymptomatic bacteriuria with the incidence of symptomatic bacteriuria, hypertensive disorders in pregnancy (HDP) and pre-term delivery. The matched paired pregnant mothers werefollowed monthly interval up to delivery. The prevalence of asymptomatic bacteriuria was 12% among the pregnant mothers in rural Rajshahi. E. Coli was the commonest causative agent of both asymptomatic and symptomatic bacteriuria. The results of this study suggest that asymptomatic bacteriuria were more prone to develop symptomatic bacteriuria, hypertensive disorders in pregnancy and pre-term delivery than that of the healthy mothers (without bacteriuria). Screening of bacteriuria in pregnancy and proper treatment must be considered as an essential part of antenatal care in this rural community.