The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy.

BACKGROUND: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy. METHODS: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively. RESULTS: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes. CONCLUSION: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system.

Effect of a High-Fat Diet and Probiotic Supplementation on the Gut Microbiota of Maternal Mice at Term Pregnancy and Offspring at Three-Week Postpartum.

The effects of probiotics on the gut microbiota in maternal mice-fed high-fat diet (HFD) during pregnancy and offspring are still unknown. We aimed to evaluate the effect of high-fat diet and probiotic supplementation on the gut microbiota of maternal mice at term pregnancy and offspring at three-week postpartum. Female pregnant Kunming mice were randomly divided into four groups: mice on a control diet (MC), mice on HFD (MHF), mice on a control diet and probiotics (MCP), and mice on HFD and probiotics (MHFP). The result showed that MHF had significantly reduced Bacteroidetes and Muribaculaceae (P < 0.05) and increased Firmicutes/Bacteroidetes ratio vs. MC. Lachnospiraceae_NK4A136_group and Alistipes reduced (P < 0.05), and Firmicutes/Bacteroidetes ratio significantly increased in MCP vs. MC. There was no significant difference between MHF and MHFP. Higher levels of Prevotella, Prevotellaceae, and Streptococcaceae were found in mice offspring on HFD (OHF) vs. mice offspring on a control diet (OC) (P < 0.05, respectively). Bacteroidia, Bacteroidota, Bacteroidales, and Muribaculaceae decreased markedly in mice offspring on a control diet and probiotics (OCP) vs. OC (P < 0.05, respectively), while Firmicutes, Lactobacillales, Lactobacillaceae, and Lactobacillus significantly increased in OCP (P < 0.05, respectively). There was no significant difference between the OHF and mice offspring on HFD and probiotics (OHFP). The findings suggest that the gut microbial composition of pregnant mice and offspring were altered to some extent due to HFD or probiotic intervention. Further, maternal mice on HFD and offspring were less affected by probiotic supplementation.

Effect of breast milk with or without bacteria on infant gut microbiota.

BACKGROUND: The breast milk microbiome could be a source of infant intestinal microbiota. Several studies have found that some breast milk is extremely low in bacteria or is even sterile. There are limited studies on the effect of milk without bacteria on the infant gut microbiota. The purpose of this study was to investigate the gut microbiota of infants fed with bacterial milk or sterile milk. Meanwhile, we attempted to find the cause of undetectable bacteria in milk. METHODS: A total of 17 healthy pregnant women and 17 infants were enrolled in this study. Fecal samples were collected from full-term pregnant women. Milk samples and infant fecal samples were collected on the 14th postnatal day. Breast milk and fecal samples were examined using 16S rRNA sequencing technology. Pregnant women and infants were grouped according to milk with or without bacteria. To compare the differences in gut microbiota and clinical characteristics between groups. RESULTS: Bacteria were detected in 11 breast milk samples, and the bacterial detection rate was 64.7%. Infants fed with bacterial milk showed higher Shannon index and Simpson index (P = 0.020, P = 0.048), and their relative abundance of Lachnospirales, Lachnospiraceae and Eggerthellaceae was markedly higher. In addition, there were more bacterial associations in the co-occurrence network of infants fed with bacterial milk. Pregnant women with sterile and bacterial breast milk showed no significant differences in their clinical characteristics, and microbial composition and diversity. CONCLUSIONS: Some breast milk from healthy postpartum women failed to be sequenced due to low microbial DNA quantities or is sterile. Research is needed to explore the reasons for this phenomenon. Infants fed with bacterial milk had higher Alpha diversity and more complex microbiota networks. These findings provide novel insight into milk microbiota and infant gut microbiota.

Differences in cognition, short-chain fatty acids and related metabolites in pregnant versus non-pregnant women: a cross-sectional study.

BACKGROUND: Pregnancy induces cognitive reorganization which can lead to mental disorders. The aim of this study is to determine differences in cognitive scores, short-chain fatty acids (SCFAs) and related metabolites between pregnant and non-pregnant participants. METHODS: This cross-sectional study included 67 full-term pregnant women and 31 non-pregnant women. We compared scores of mental state and cognitive assessment tests, as well as serum concentrations of SCFAs, hormones, inflammatory factors, and neurotransmitters between these groups. RESULTS: Scores for information processing speed, immediate visual memory, motor response speed and accuracy, execution ability and verbal use ability in the pregnant group were lower than those in the non-pregnant group (p < 0.05 for all tests). Total serum SCFAs in the pregnant group were significantly lower than those in the non-pregnant group (P = 0.031). Among them, acetate and propionate were significantly decreased (P = 0.013 and 0.037, respectively) whereas butyrate was significantly increased (P = 0.035). Serum peptide YY, glucagon-like peptide-1, γ-aminobutyric acid, and dopamine showed no differences between the two groups. However, cortisol, adrenocorticotropic hormone, and acetylcholine were significantly increased in the pregnant group as compared with the non-pregnant group (P = 0.039, 0.016, and 0.012, respectively). Tumor necrosis factor-α was increased and interleukin-10 significantly decreased in the pregnant group (P = 0.045 and 0.019, respectively). CONCLUSION: According to our study findings, cognitive reorganization in the third trimester of pregnancy showed that both the passive storage capacity of working memory and the executive function of online information processing were decreased to varying degrees. At the same time, the changes in total SCFAs, the proportions of SCFAs and related metabolites were also detected. These changes in the internal environment may be increasing the risk of perinatal mental illness.

The effect of probiotic supplementation during pregnancy on the interaction network of vaginal microbiome.

AIM: To evaluate the effect of probiotic supplementation on the vaginal microbiome and provide the effective evidences for clinical management of pregnant women. METHODS: A total of 28 healthy pregnant women at 32 weeks of gestation were enrolled. The women were divided randomly to the probiotic group where they were prescribed with 2 g combined probiotics daily (13 cases) during the third trimester of pregnancy or to the control group (15 cases) on a voluntary basis. Their vaginal samples were taken for analyzing microbiome with the 16S rDNA amplicon sequencing of V4 region. RESULTS: There was no significant difference on the clinical characteristics between the probiotic and control groups. The complexity of vaginal microbial network increased from 32 weeks of gestation to antepartum. Lactobacillus was the dominant microbiota. The probiotic supplementation had no obvious influence on the structure of the vaginal microbiome, whereas the relationships of some pivotal vaginal microbiota at the genus level changed in the probiotic group. CONCLUSION: The vaginal microbiome varied during the third trimester of pregnancy. The features of the vaginal microbiota after probiotic supplementation had shifted and the interaction network had the tendency to be loose. The probiotic supplementation may be useful in regulating the interaction network of vaginal microbiome.

Effects of normal pregnancy on maternal EEG, TCD, and cerebral cortical volume.

OBJECTIVE: Pregnancy causes many changes in our body and some of them may affect our ability of learning and memory. We examined the cerebral cortical volume of brain during pregnancy and measured changes in the brain electrical activity and cerebral blood flow. METHOD: 35 women (20 normal full-term primigravida and 15 non-pregnant women) received the Electroencephalography (EEG) and Transcranial Doppler ultrasonography (TCD). 8 non-pregnant women and 9 primigravida after vaginal delivery underwent brain magnetic resonance imaging (MRI) voluntarily within 24 h. RESULTS: Compared with the non-pregnant, changes were shown by EEG through electrodes of T5, Pz, Cz, T6, F3 and F8. The results displayed increased activity in the central parietal area of pregnant women, while that in the temporoparietal junction decreased. The result of TCD revealed that pulsation index (PI) values of left and right internal and external carotid arteries were asymmetrical, but they all decreased in pregnancy. Atrophy of cortical volume had been found in many brain functional areas of pregnant women. The percentage of atrophy varied between 6.76% and 13.17%. CONCLUSION: Atrophy of cerebral cortex, changes in cerebral blood flow and neuron electrophysiology may be the physiological basis of the emotional, cognitive changes in pregnant women.

Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy.

BACKGROUND: Probiotic supplementation has been shown to be beneficial and is now widely promoted as an auxiliary medicine for maternal health, but the underlying mechanism is still unclear. Thus, this study aimed to explore the effects of probiotic supplementation on the placental autophagy-related proteins LC3 and Beclin1. METHOD: A population-based cohort of specimens was collected under sterile conditions from 37 healthy nulliparous pregnant women who underwent systemic examination and delivered at the First Affiliated Hospital of Jinan University (Guangzhou, China). At 32 weeks of gestation, the pregnant women in the probiotic group were orally supplemented with golden bifid, and the pregnant women in the control group received no probiotic. Pregnant women with pregnancy-associated complications were excluded in the follow-up period, and 25 pregnant women undergoing spontaneous delivery were enrolled. The placental tissue specimens were collected at term. Western blotting was used to detect the protein expression, and qRT-PCR was used to detect the mRNA expression of the placental autophagy-related proteins LC3 and Beclin1. RESULTS: ①There was no significant difference in the expression levels of either LC3 or Beclin1 protein between the two groups (P > 0.05). ②Probiotic supplementation induced a modest but not significant decrease in the content of LC3-mRNA with a significant decrease in the content of Beclin1-mRNA (P < 0.05). CONCLUSION: Our study indicates that probiotic supplementation may reduce Beclin1-mRNA levels.

Eliciting women's preference for prenatal testing in China: a discrete choice experiment.

BACKGROUND: Pregnancy tests can be used for the early diagnosis of fetal problems and can prevent abnormal birth in pregnancies. Yet, testing preferences among Chinese women are poorly investigated. METHODS: We developed a Discrete Choice Experiment with 5 attributes: test procedure, detection rate, miscarriage rate, time to wait for result, and test cost. By studying the choices that the women make in the hypothetical scenarios and comparing the attributes and levels, we can analyze the women's preference of prenatal testing in China. RESULTS: Ninety-two women completed the study. Respondents considered the test procedure as the most important attribute, followed by detection rate, miscarriage rate, wait time for result, and test cost, respectively. The estimated preference weight for the non-invasive procedure was 0.928 (P < 0.0001). All other attributes being equal, the odds of choosing a non-invasive testing procedure over an invasive one was 2.53 (95% confidence interval, 2.42-2.64; P < 0.001). Participants were willing to pay up to RMB$28,810 (approximately US$4610) for a non-invasive test, RMB$6061(US$970) to reduce the miscarriage rate by 1% and up to RMB$3356 (US$537) to increase the detection rate by 1%. Compared to other DCE (Discrete Choice Experiment) studies regarding Down's syndrome screening, women in our study place relatively less emphasis on test safety. CONCLUSIONS: The present study has shown that Chinese women place more emphasis on detection rate than test safety. Chinese women place great preference on noninvasive prenatal testing, which indicate a popular need of incorporating noninvasive prenatal testing into the health insurance coverage in China. This study provided valuable evidence for the decision makers in the Chinese government.

Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency.

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Although the etiology of ICP is not fully understood thus far, some genetic factors might contribute to the development of this condition. Sodium-taurocholate cotransporting polypeptide (NTCP), the protein encoded by the gene Solute Carrier Family 10, Member 1 (SLC10A1), is the primary transporter expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile salts from the plasma. NTCP deficiency arises from biallelic SLC10A1 mutations which impair the NTCP function and cause intractably elevated levels of total bile acids (TBA) in the plasma (hypercholanemia). In this study, all the SLC10A1 exons and their flanking sequences were analyzed by Sanger sequencing to investigate the etiology for hypercholanemia in two male infants aged 2 and 20 months, respectively, from two unrelated families. As a result, both patients are homozygous for the reported pathogenic variant c.800C>T (p.Ser267Phe) that could impair the NTCP function to uptake bile acids, and the diagnosis of NTCP deficiency was thus made. Their mothers are also homozygotes of the same variant and both had been diagnosed to have ICP in the third trimester, with one of them undergoing cesarean section. The father of the first patient in this paper has the same SLC10A1 genotype c.800C>T/c.800C>T, also exhibiting slight hypercholanemia with a plasma TBA level of 21.5 µmol/L. In conclusion, we suggest that with hypercholanemia being a common laboratory change, NTCP deficiency may be a genetic factor leading to ICP and even cesarean section in clinical practice.

A preliminary study of uterine scar tissue following cesarean section.

AIM: To compare smooth muscle cells, type I collagen, and apoptosis of the lower uterine segment of women who had/without a prior cesarean delivery. METHODS: Alpha smooth muscle actin (α-SMA), type I collagen, and nuclear apoptosis were compared between the groups from lower uterine segment. Twenty-eight controls and 82 with one prior cesarean delivery were included. The women with a prior cesarean section were classified by time since the surgery: ≤3 years, >3 and ≤5 years, >5 and ≤7 years, >7 and ≤9 years, and >9 years. RESULTS: Smooth muscle volume density (VD) % was significantly lower in women who had cesarean sections in first three groups than in the controls (all, P<0.01). Type I collagen VD% was similar among all groups and the controls. The number of apoptotic nuclei in the lower uterine segment of the scarred group was greater up to 3 years after surgery and less than in the control at 7-9 years. The number of non-apoptotic nuclei in the scarred group was greater than controls up to 7 years after surgery. CONCLUSION: The lower uterine segment scar becomes stable at 3 years after cesarean delivery, and by 9 years, the scar is mature.

Medical nutrition treatment of women with gestational diabetes mellitus by a telemedicine system based on smartphones.

AIM: To explore whether WeChat platform-based treatment of women with gestational diabetes mellitus (GDM) reduces the risk of perinatal complications and explore factors affecting gestational age at delivery. METHODS: Pregnant women with GDM (n = 107) and normal glucose tolerance (n =50, group C) according to oral glucose tolerance test (OGTT) results during gestational weeks 24-28 were included. Women with GDM were divided into groups A (n =57) and B (n =50) according to informed consent. According to GDM treatment norms, group B was given routine outpatient treatment and health education guidance. In addition to the interventions in group B, group A was given access to both a smartphone-based telemedicine system and articles providing continuous health education. The PBG level in groups A and B was compared, as were differences in maternal and fetal outcomes. Data were analyzed by t-test, analysis of variance (anova), chi-square test and multiple linear regression, with P < 0.05 considered significant. RESULTS: Fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG) were significantly lower and premature delivery was significantly less likely in group A than in group B (all P < 0.05). Compared with group B, caesarean section was more likely in group A (P < 0.05). Pregnancy-induced hypertension had a higher incidence in group B than in group C (P < 0.05). Gestational age at delivery was associated with OGTT2h, premature fetal membrane rupture and self-monitoring of blood glucose. CONCLUSION: GDM treatment based on the WeChat platform effectively reduces FBG and 2-h PBG and may improve pregnancy outcomes. However, 1-h PBG was not affected by treatment. Obstetricians should consider the OGTT2h value to increase gestational age at delivery.

[Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency].

OBJECTIVE: To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them. METHODS: The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies. RESULTS: Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated. CONCLUSION: Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.

The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy.

BACKGROUND/AIMS: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. METHODS: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 ±16.29 of gestation) and late (day 268.12 ±13.04 of gestation) pregnancy. RESULTS: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. CONCLUSIONS: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies.

Telbivudine during the second and third trimester of pregnancy interrupts HBV intrauterine transmission: a systematic review and meta-analysis.

UNLABELLED: BECKGROUND: Evaluate the efficacy and safety of telbivudine during the 2nd and 3rd trimester of pregnancy in intrauterine transmission of hepatitis B virus (HBV). Based on the principle of Cochrane systematic reviews, a database was constructed from Medline, EMBASE, Cochrane Library, the US National Science Digital Library (NSDL), the China Biological Medicine Database (CBM-disc), and contact with Chinese experts in the field from November 2006 to February 2013. METHODS: The Critical Appraisal Skills Programme (CASP) of Oxford, Cochrane Collaboration's tool, and Review Manager Version 5.0 (Rev-Man 5.0) for assessing the quality of clinical trials, risk of bias, and statistical analysis was used. We analyzed the effects and safety of telbivudine treatment on intrauterine mother-to-child transmission (MTCT) of HBV from HBsAg and HBV-DNA positive mothers. All newborns received an immune prophylaxis schedule consisting of simultaneous hepatitis B virus vaccine and hepatitis B immunoglobulin (HBIG) postpartum. Of 32 studies, 7 studies fulfilled the inclusion criteria in the study. RESULTS: Either the Mantel-Haenszel or Inverse Variance fixed-effects model or Mantel-Haenszel or Inverse Variance random-effects model was applied for all analyses indicated by odds ratio (OR) and 95% confidence interval (CI). The meta-analysis based on new onset of HBsAg seropositivity of infants at 6-12 months postpartum revealed that the control group had an intrauterine transmission rate of 8.25-42.31%. This rate was reduced to 0-14.29% in the telbivudine treatment group (OR 0.09, 95% CI 0.04-0.22, including seven trials, p < 0.001). The rates of intrauterine transmission based on new onset of HBV DNA seropositivity of infants at 6-12 months postpartum were 8.25-19.23% in the control group and 0 - 3.57% in the treatment group (OR 0.07, 95% CI 0.02-0.22, p < 0.001, including only five trials, since two trials had no data on HBV DNA in infants). With the exception of CK elevations, adverse effect frequencies were similar in both groups. CONCLUSIONS: Telbivudine is an effective and safe drug for preventing intrauterine transmission of HBV.

Expression of interferon-γ in decidual natural killer cells from women with hypertensive disorder complicating pregnancy.

AIM: Hypertensive disorder complicating pregnancy (HDCP) is one of the most frequent and serious pregnancy-related diseases, which is closely related to disorders of the maternal immune system, especially the local immune microenvironment of the maternal-fetal interface. Uterine decidual natural killer (dNK) cells are the major immune cells in the maternal-fetal interface and they play an important role in establishing and maintaining a normal pregnancy. The aim of this study was to investigate the phenotype and function of dNK cells from women with HDCP. MATERIAL AND METHODS: Decidual tissues were collected from women with normal pregnancy (normal control group, n = 15 cases) and HDCP (HDCP group, n = 20 cases), respectively. The mononuclear cells were extracted from tissues and flow cytometry (FCM) was utilized to sort out dNK cells. The phenotypes of dNK cells (CD56(bright)CD16⁻CD3⁻ vs CD56(dim)CD16⁺CD3⁻) were detected by FCM. After being co-cultured with Phorbol 12-myristate 13-acetate, ionomycin and monensin, the expression level of interferon (IFN)-γ in the dNK cells was detected by FCM. RESULTS: The phenotypes of dNK cells from the two groups were dominated by the CD56(bright)CD16⁻CD3⁻ subset, with no significant statistical difference (P < 0.05). The expression level of IFN-γ in the dNK cells from women with HDCP was on a lower trend than those from women with normal pregnancy, having significant statistical difference (P = 0.000 < 0.05). CONCLUSIONS: Our results indicated that although the phenotype of dNK cells from women with HDCP is of no difference, their functions are abnormal. Impaired cell function leads to a lower expression level of IFN-γ and this may account for one of the pathogeneses of HDCP.

The influence of the oral microbiota in full-term pregnant women on immune regulation during pregnancy.

BACKGROUND: This study aims to conduct a preliminary exploration of the correlation between the oral microbiota of full-term pregnant women and both local placental immunity and the systemic immune system of the mother. METHODS: A total of 26 pregnant women participated in this study, with samples collected from oral swabs, placental tissue, and peripheral venous blood. High-throughput sequencing was used to examine the oral microbial community. Flow cytometry was employed to assess immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid bead chip technology were utilized to detect cytokines in both placental tissue and peripheral venous blood. RESULTS: In placental tissue, The oral microbial community is primarily negatively correlated with placental CD3+CD4+CD8+T cells and positively correlated with placental IL-5. In the peripheral blood, The oral microbial community is primarily positively correlated with maternal systemic immune parameters, including CD3+CD4+ T cells and the CD4+/CD8+ ratio, as well as positively correlated with peripheral IL-18. CONCLUSIONS: The oral microbiota of full-term pregnant women participates in the regulatory function of the maternal immune system. Meanwhile, the oral microbial community may also be an important factor mediating local immune regulation in the placenta.

Effect of probiotic administration during pregnancy on the functional diversity of the gut microbiota in healthy pregnant women.

Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women. IMPORTANCE: Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.

Origin of the neonatal gut microbiota and probiotic intervention: a randomized controlled trial.

Objective: This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Methods: Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. Results: We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

Multi-omics analysis reveals the associations between altered gut microbiota, metabolites, and cytokines during pregnancy.

For embryo implantation and fetal development, the maternal immune system undergoes dramatic changes. The mechanisms involved in inducing alterations of maternal immunity have not been fully clarified. Gut microbiome and metabolites were thought to influence the host immune response. During normal pregnancy, notable changes occur in the gut microbiota and metabolites. However, the relationship of these alterations to immune function during pregnancy remains unclear. In this study, we examined gut microbiota, fecal metabolites, plasma metabolites, and cytokines in pregnant women and non-pregnant women. Our findings revealed that, in comparison to non-pregnant women, pregnant women exhibit a significant increase in the relative abundance of Actinobacteriota and notable differences in metabolic pathways related to bile acid secretion. Furthermore, there was a marked reduction in pro-inflammatory cytokines levels in pregnant women. Correlation analyses indicated that these alterations in cytokines may be linked to specific gut bacteria and metabolites. Bacteria within the same microbial modules exhibited consistent effects on cytokines, suggesting that gut bacteria may function as functional groups. Mediation analysis further identified that certain bacteria might influence cytokines through metabolites, such as bile acids and arachidonic acid. Our findings propose potential biological connections between bacteria, metabolites, and immunity, which require further validation in future studies.IMPORTANCEA great number of studies have focused on diseases induced by intestinal microecological disorders and immune imbalances. However, the understanding of how intestinal microbiota interacts with immunity during normal pregnancy, which is fundamental to studying pathological pregnancies related to intestinal microbiota disturbances, has not been well elucidated. Our study employed multi-omics analysis to discover that changes in gut microbiota and metabolites during pregnancy can impact immune function. In addition, we identified several metabolites that may mediate the effect of gut microbes on plasma cytokines. Our study offered new insights into our understanding of the connections between the gut microbiome, metabolome, and the immune system during pregnancy.

Normal weight obesity is associated with lower AFC and adverse IVF outcomes.

Background: Body weight could be classified into underweight, normal weight and overweight according to percentage of body fat (%BF), and normal weight obesity (NWO) is defined as a normal BMI but a high %BF. While the impact of NWO in women fecundity remain unknow. Therefore, this study aimed to investigate the associations between %BF and reproductive outcomes among in vitro fertilization (IVF) women with normal BMI. Methods: A total of 469 women were included in this study and were classified into low %BF, normal %BF and high %BF according to previous study. Multivariate generalized regression models were employed to evaluate the associations of %BF with ovarian reserve parameters, IVF outcomes and early pregnancy outcomes. We further run sensitivity analyses by restricted the analysis to young women and those only with tubal factor, respectively. Results: About 32.2% of normal BMI women were misclassified according %BF, with 16.4% of them were low %BF and 15.8% were high %BF. The high %BF group had significantly lower antral follicle count (AFC) than normal %BF groups, and the AFC showed a tendency of decrease as %BF increased. In sensitivity analysis in young women, high %BF group also had significantly lower number of good-quality embryos when compared to normal %BF groups. The results expanded to all IVF outcomes when analysis restricted to tubal factor women. Conclusion: In summary, misclassifications of body weight status based on BMI are common according to %BF, and NWO is associated with adverse reproductive outcomes.