The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge. 

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Microbiota medicine: towards clinical revolution

https://translational-medicine.biomedcentral.com/track/pdf/10.1186/s12967-022-03296-9

Abstract Background Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. Methods A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis ( n =13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran’s Q statistics were used to quantify the heterogeneity of instrumental variables. Results Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64–0.89, P = 8.03 × 10 −4 ). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60–0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62–0.93, P = 8.76 × 10 −3 ), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63–0.91, P = 2.43 × 10 −3 ), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65–0.92, P = 3.77 × 10 −3 ), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74–0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Conclusions This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms. 

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Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.

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Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.

Preeclampsia is a devastating hypertensive pregnancy disorder that currently affects 2%-8% of pregnancies worldwide. It is associated with maternal and fetal mortality and morbidity and adverse health outcomes both in mom and offspring beyond pregnancy. The pathophysiology is not completely understood, and there are no approved therapies to specifically treat for the disease, with only few therapies approved to manage symptoms. Recent advances suggest that aberrations in the composition of the microbiome may play a role in the pathogenesis of various diseases including preeclampsia. The maternal and uteroplacental environments greatly influence the long-term health outcomes of the offspring through developmental programming mechanisms. The current review summarizes recent developments on the role of the microbiome in adverse pregnancy outcomes with a focus on preeclampsia. It also discusses the potential role of the maternal microbiome in fetal programming; explores gut-targeted therapeutics advancement and their implications in the treatment of preeclampsia.

Maternal microbiome in preeclampsia pathophysiology and implications on offspring health.

BACKGROUND Preeclampsia (PE) is a serious complication that affects maternal and perinatal outcomes. However, the mechanisms have not been fully explained. This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second (T2) and third trimesters (T3). METHODS In this nested case-control study, which was conducted at Nanjing Maternity and Child Health Care Hospital, fecal samples from 25 PE patients (25 fecal samples obtained in T2 and 15 fecal samples obtained in T3) and 25 matched healthy controls (25 fecal samples obtained in T2 and 22 fecal samples obtained in T3) were collected, and the microbiota were analyzed using 16S rRNA gene sequencing. The diversity and composition of the microbiota of PE cases and controls were compared. RESULTS No significant differences in diversity were found between the PE and control groups (P > 0.05). In the control group, from T2 to T3, the relative abundances of Proteobacteria (median [Q1, Q3]: 2.25% [1.24%, 3.30%] vs. 0.64% [0.20%, 1.20%], Z = -3.880, P < 0.05), and Tenericutes (median [Q1, Q3]: 0.12% [0.03%, 3.10%] vs. 0.03% [0.02%, 0.17%], Z = -2.369, P < 0.05) decreased significantly. In the PE group, the relative abundance of Bacteroidetes in T2 was lower than in T3 (median [Q1, Q3]: 18.16% [12.99%, 30.46%] vs. 31.09% [19.89%, 46.06%], Z = -2.417, P < 0.05). In T2, the relative abundances of mircrobiota showed no significant differences between the PE group and the control group. However, in T3, the relative abundance of Firmicutes was significantly lower in the PE group than in the control group (mean ± standard deviation: 60.62% ± 15.17% vs. 75.57% ± 11.53%, t = -3.405, P < 0.05). The relative abundances of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group (median [Q1, Q3]: 31.09% [19.89%, 46.06%] vs. 18.24% [12.90%, 32.04%], Z = -2.537, P < 0.05; 1.52% [1.05%, 2.61%] vs. 0.64% [0.20%, 1.20%], Z = -3.310, P < 0.05; 0.75% [0.20%, 1.00%] vs. 0.01% [0.004%, 0.023%], Z = -4.152, P < 0.05). Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes, class Bacteroidia and order Bacteroidales were increased in the PE group, while those of the phylum Firmicutes, the class Clostridia, the order Clostridiales, and the genus unidentified Lachnospiraceae were decreased in the PE group; and these differences were identified as taxonomic biomarkers of PE in T3. CONCLUSION From T2 to T3, there was an obvious alteration in the gut microbiota. The gut microbiota of PE patients in T3 was significantly different from that of the control group.

Zhong-Hua Shi

Papers

Gut microbiota dysbiosis in preeclampsia patients in the second and third trimesters.