Exploring the Association between Anxiety, Depression, and Gut Microbiota during Pregnancy: Findings from a Pregnancy Cohort Study in Shijiazhuang, Hebei Province, China.

Negative emotions and gut microbiota during pregnancy both bear significant public health implications. However, the relationship between them has not been fully elucidated. This study, utilizing data from a pregnancy cohort, employed metagenomic sequencing to elucidate the relationship between anxiety, depression, and gut microbiota's diversity, composition, species, and functional pathways. Data from 87 subjects, spanning 225 time points across early, mid, and late pregnancy, were analyzed. The results revealed that anxiety and depression significantly corresponded to lower alpha diversity (including the Shannon entropy and the Simpson index). Anxiety and depression scores, along with categorical distinctions of anxiety/non-anxiety and depression/non-depression, were found to account for 0.723%, 0.731%, 0.651%, and 0.810% of the variance in gut-microbiota composition (p = 0.001), respectively. Increased anxiety was significantly positively associated with the abundance of Oscillibacter sp. KLE 1745, Oscillibacter sp. PEA192, Oscillibacter sp. KLE 1728, Oscillospiraceae bacterium VE202 24, and Treponema socranskii. A similar association was significantly noted for Oscillibacter sp. KLE 1745 with elevated depression scores. While EC.3.5.3.1: arginase appeared to be higher in the anxious group than in the non-anxious group, vitamin B12-related enzymes appeared to be lower in the depression group than in the non-depression group. The changes were found to be not statistically significant after post-multiple comparison adjustment.

Spatiotemporal patterns of the pregnancy microbiome and links to reproductive disorders.

The microbiome of females undergoes extensive remodeling during pregnancy, which is likely to have an impact on the health of both mothers and offspring. Nevertheless, large-scale integrated investigations characterizing microbiome dynamics across key body habitats are lacking. Here, we performed an extensive meta-analysis that compiles and analyzes microbiome profiles from  >10,000 samples across the gut, vagina, and oral cavity of pregnant women from diverse geographical regions. We have unveiled unexpected variations in the taxonomic, functional, and ecological characteristics of microbial communities throughout the course of pregnancy. The gut microbiota showed distinct trajectories between Western and non-Western populations. The vagina microbiota exhibited fluctuating transitions at the genus level across gestation, while the oral microbiota remained relatively stable. We also identified distinctive microbial signatures associated with prevalent pregnancy-related disorders, including opposite variations in the oral and gut microbiota of patients with gestational diabetes and disrupted microbial networks in preterm birth. This study establishes a comprehensive atlas of the pregnancy microbiome by integrating multidimensional datasets and offers foundational insights into the intricate interplay between microbes and host factors that underlie reproductive health.

Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.

PURPOSE: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy complication. However, the pathogenesis of ICP is currently unclear. METHODS: We analyzed the placenta samples of 10 normal and 10 ICP pregnant women. the expressions of circ0060731, miR-21-5p, and their downstream target genes PDCD4, ESR1, and apoptotic protein cleaved-caspase3 were detected in the cell model. RESULTS: The expression of Circ_0060731, PDCD4, ESR1, and caspase-3 was higher in the ICP placenta tissue than in the control group, and the expression of miR-21-5p was lower in the ICP group than in the control group. In HTR8/Svneo cells treated with TCA, the expression/levels of Circ_0060731, PDCD4, ESR1, and caspase-3 were significantly higher in the ICP group than in the control group, and miR-21-5p was significantly lower in the ICP group than in the control group. Lentiviral knockdown of miR-21-5p significantly increased the expressions of its downstream genes of PDCD4 and ESR1, and also increased cell apoptosis. Overexpression of miR-21-5p significantly reduced the expression of PDCD4 and ESR1 and reduced cell apoptosis. The dual-luciferase experiment showed that both PDCD4 and ERS1 were the target genes of miR-21-5p. CONCLUSION: Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway could induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.

Placental acute inflammation infiltrates and pregnancy outcomes: a retrospective cohort study.

Chorioamnionitis can be either an infection or a sterile inflammation. This study aims to analyze the prevalence of acute inflammatory lesions of the placenta, the association with a positive result of the microbiological examination, and the fetal-maternal outcomes. This retrospective study considered all single, consecutive pregnancies and their placental pathological examination during 2014-2017. The evidence of funisitis, chorionic vasculitis, and chorioamnionitis was assessed by a pathologist, including stage and grade. Moreover, maternal fever, placental microbiological examination, and neonatal outcomes were also recorded. Among the 5910 pregnancies in the considered period, 1770 had a placental pathological examination, and 358 (6.06%) had acute placental inflammation. Microbiological examination was performed in 125 cases, revealing 64 cases with a positive microbiological outcome. In the presence of acute placental inflammation, there was a higher rate of neonatal cardiopulmonary resuscitation, admission to neonatal intensive care unit, and postnatal death of the newborn. Multivariate analysis inferred that acute inflammation of membranes was a risk factor for neonatal cardiopulmonary resuscitation (OR 2.12; CI.95 1.36-3.31; p < 0.05), acute funisitis was a risk factor for admission to intensive neonatal care unit (OR 3.2; CI.95 1.67-6.12; p < 0.05), and chorionic vasculitis was a risk factor for postnatal death of the newborn (OR 5.38; CI.95 1.37-21.06; p < 0.05). The prevalence of chorioamnionitis was 6.06%, and about half of the cases were sterile inflammation. Chorioamnionitis was associated with higher rates of adverse fetal and neonatal outcomes; in particular, chorionic vasculitis was a risk factor for postnatal death.

Association of tuberculosis treatment with pregnancy complications: A protocol for systematic review and meta-analysis.

BACKGROUND: The increasing burden of tuberculosis (TB) remains a very serious concern around the world, and account for a decreased quantity and quality of life. However, there is a limited epidemiology of the association of TB treatment with pregnancy. We aim to assess the effects of TB treatment in pregnancy complications. METHODS: This will be a systematic review and meta-analysis of published studies on the association of TB treatment with pregnancy, retrieved from ScienceDirect, Web of Science, LILACS, Pubmed, Google scholar, Embase, Medline, ResearchGate, EBSCOhost and Cochrane library databases. The eligibility of the studies will be screened in accordance to the selection criteria by two independent reviewers. The quality and risk of bias of eligible studies will be performed by both reviewers using the Hoy tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool in accordance to the measured outcomes (Hypertension in pregnancy, Pre-eclampsia, Hypertensive disorders of pregnancy, Fetal growth restriction, Miscarriage and Recurrent spontaneous abortion). A data charting table will be used to extract background information and process the data items from each eligible study. The data will be analysed using Review Manager 5.3 (RevMan 5.3) software. Generic Inverse Variance method will be used for meta-analysis of both, individually and cluster randomized trials. ETHICS AND DISSEMINATION: The review and meta-analysis will not require ethical approval and the findings will be published in peer-reviewed journals and presented at local and international conferences. In addition, the study findings will be made accessible to the national committee of TB to formulate TB guidelines for their respective settings. SYSTEMATIC REVIEW REGISTRATION: International prospective Register of Systematic Reviews (PROSERO) number: CRD42021231872.

Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women.

Objective: To evaluate the small intestinal bacterial overgrowth (SIBO) of subclinical hypothyroidism of pregnant women, and explore their possible relevance. Methods: In total, 224 pregnant women with subclinical hypothyroidism during pregnancy (study group) and 196 pregnant women whose thyroid function was normal (control group) were enrolled in this study. Lactulose-based hydrogen and methane breath test was performed to evaluate the growth of intestinal bacteria. The serum-free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), body mass index (BMI) and gastrointestinal symptoms were detected and recorded. Results: The positive rates of SIBO were 56.7% and 31.6% in study group and control group, respectively. The levels of C response protein (CRP), abdominal distension and constipation in study group were higher than those in the control group. The risk of abdominal distension and constipation in SIBO-positive pregnant women were higher than that in SIBO-negative pregnant women, and the BMI of SIBO-positive patients in the two groups was lower than that of SIBO-negative patients in each group. In addition, the TPOAb-positive rate and TSH levels were higher but the FT4 level was lower in SIBO-positive patients compared to SIBO-negative patients in study group. Conclusion: The occurrence of subclinical hypothyroidism is related to SIBO, and the excessive growth of small intestinal bacteria may affect gastrointestinal symptoms. Clinical Trial: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026326.

Perinatal Infections With Ureaplasma.

Ureaplasma species are increasingly recognized as relevant pathogens in prenatal, perinatal and postnatal morbidity. They are commonly found as commensals on the mucous membranes of the lower urogenital tract of pregnant women, but when ascending, they can cause bacterial vaginosis, chorioamnionitis, premature birth and postnatal morbidities such as bronchopulmonary dysplasia, and early-onset neonatal sepsis and meningitis. The detection of Ureaplasma species is challenging and is not covered by routine diagnostics, and current empiric antibiotic treatment in neonates suspected of infection is not directed against Ureaplasma species. The aim of this review is to discuss the pathophysiology of Ureaplasma infections, the clinical consequences and the current difficulties in diagnosis and treatment by providing an overview of the current literature.

Application of methane and hydrogen-based breath test in the study of gestational diabetes mellitus and intestinal microbes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. The purpose of this study was to compare the incidence of small intestinal bacterial overgrowth (SIBO) in patients with GDM and the control group by methane and hydrogen lactulose breath test (LBT), and to explore its relationship with inflammation, vitamins, and the outcomes of maternal and child. METHODS: LBT was detected in 220 GDM patients, 160 pregnancy control patients and 160 pre-pregnancy control patients. The fasting blood glucose, white blood cells, vitamin A, D, E, neonatal weight, neonatal blood glucose and so on were compared and analyzed. RESULTS: There was no statistical significance in the general data of the three groups. The proportion of abdominal distension in the GDM group was higher than that in the other two groups (P < 0.001). The positive rates of SIBO + in GDM group, gestational control group and pre-pregnancy control group were 54.55%, 27.50% and 14.38%, respectively. The average abundance of hydrogen and methane in GDM group was significantly higher than that in control group at each time point. In the GDM group, SIBO + subjects had higher levels of fasting blood glucose, glycoglycated hemoglobin, C-reactive protein, neonatal weight, and lower levels of vitamin D and neonatal blood glucose (P < 0.001). CONCLUSION: Patients with GDM have a high incidence of SIBO, and SIBO may further increase their blood glucose by affecting inflammatory response and vitamin level, and even affect the outcome of mother and child.

A systematic review of the factors influencing microbial colonization of the preterm infant gut.

Prematurity coupled with the necessary clinical management of preterm (PT) infants introduces multiple factors that can interfere with microbial colonization. This study aimed to review the perinatal, physiological, pharmacological, dietary, and environmental factors associated with gut microbiota of PT infants. A total of 587 articles were retrieved from a search of multiple databases. Sixty studies were included in the review after removing duplicates and articles that did not meet the inclusion criteria. Review of this literature revealed that evidence converged on the effect of postnatal age, mode of delivery, use of antibiotics, and consumption of human milk in the composition of gut microbiota of PT infants. Less evidence was found for associations with race, sex, use of different fortifiers, macronutrients, and other medications. Future studies with rich metadata are needed to further explore the impact of the PT exposome on the development of the microbiota in this high-risk population.

The impact of the gut microbiota on the reproductive and metabolic endocrine system.

As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.

Oral microbiome and pregnancy: A bidirectional relationship.

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

Case Report: Severe Craniofacial Coccidioidomycosis in a Pregnant Woman.

Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis and Coccidioides posadasii. The lungs are the most common and often the initial site of involvement, and the non-pulmonary presentation is infrequent. We describe an unusual case of primary craniocutaneous coccidioidomycosis in a pregnant woman with infected bilateral periorbital nodules, intense pain at paranasal sinuses, and several osteolytic skull lesions. The analysis of 54 cases available in the literature makes us suggest that the area between the United States and Mexico is a risk zone for primary cutaneous coccidioidomycosis.

Plasma Lipid Profile and Intestinal Microflora in Pregnancy Women With Hypothyroidism and Their Correlation With Pregnancy Outcomes.

Objective: To investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes. Methods: In total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed. Results: Patients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05). Conclusion: The lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.

Probiotic intervention as a potential therapeutic for managing gestational disorders and improving pregnancy outcomes.

Recent molecular investigations have significantly developed our knowledge of the characteristics of the reproductive microbiome and their associations with host responses to provide an ideal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy as well as to provide a successful in vitro fertilization and appropriate reproductive outcomes. In this context, the establishment of microbial homeostasis in the female reproductive tract, in various physiological periods, is a substantial challenge, which appears the application of probiotics can facilitate the achievement of this goal. So that, currently, probiotics due to its safe and natural features can be considered as a novel biotherapeutic approach. In this review, we comprehensively discuss the bacterial, fungal, and viral diversity detected in the reproductive tract, and their associations with the establishment of dysbiosis/eubiosis conditions as well as we present the significant outcomes on probiotic intervention as an efficient biotherapeutic strategy for management of gestational disorders and improve pregnancy outcomes.

Perfil de sensibilidade de uropatógenos em gestantes de um hospital de ensino do município de São Paulo / Sensitivity profile of uropathogens in pregnant women at a teaching hospital in the city of São Paulo

Objetivo: O presente estudo tem como objetivo avaliar o perfil de sensibilidade antimicrobiana do patógeno mais comum causador da infecção do trato urinário (ITU) de gestantes que foram internadas em um hospital de ensino do município de São Paulo em determinado período. Métodos: Estudo retrospectivo, transversal, quantitativo, realizado avaliando as uroculturas positivas e o perfil de sensibilidade antimicrobiana dos agentes mais comuns encontrados em ITUs das gestantes de hospital e maternidade-escola do município de São Paulo de janeiro de 2019 até janeiro de 2020. Resultados: A partir da análise de uroculturas positivas e antibiograma de 149 gestantes admitidas com quadro de infecção urinária no referido hospital no intervalo de tempo analisado, constatou-se que 83,89% dos casos apresentaram como patógeno a bactéria Escherichia coli. No âmbito da resistência bacteriana, percebeu-se que o maior índice foi encontrado no que tange a cefalotina (65%), ampicilina (58%) e ampicilina/sulbactam (45%). Ademais, a partir das análises individuais, 20 pacientes, ou seja, aproximadamente 13,42% apresentaram cepas sensíveis a todas as medicações apontadas, e as demais apresentaram resistência a, pelo menos, uma delas. Conclusão: A partir da premissa de eficácia desempenhada pelo protocolo de medicação empírica estabelecido pela instituição no tocante ao tratamento de infecção do trato urinário em gestantes, a cefalotina certamente não deveria compor o rol de drogas ofertadas às pacientes. Isso se dá, pois a sensibilidade apresentada pela Escherichia coli, patógeno que mais comumente está associado aos quadros de ITU do serviço, a essa droga é muito baixa. Já a nitrofurantoína apresentou um satisfatório espectro de cobertura, sendo a resistência à droga inferior a 10%. Com isso, conclui-se que ela deve permanecer como droga inicial para as ITUs das gestantes que chegam a essa instituição.(AU)

Objective: The present study aims to evaluate the antimicrobial sensitivity profile of the most common pathogen that causes urinary tract infection (ITU) in pregnant women who were admitted to a Teaching Hospital in the city of São Paulo in a specific period. Methods: Retrospective, cross-sectional, quantitative study carried out evaluating positive urine cultures and the antimicrobial sensitivity profile of the most common agents found in ITU of pregnant women at Teaching Maternity hospital in the city of São Paulo from January 2019 to January 2020. Results: From the of positive urine culture and antibiogram of 149 pregnant women admitted with a urinary tract infection in the referred hospital in the analyzed period of time, it was found that 83.89% of the cases presented the bacterium Escherichia coli as a pathogen. In the scope of bacterial resistance, it was noticed that the highest index was found with respect to Cephalothin (65%), ampicillin (58%) and ampicillin/sulbactam (45%). Furthermore, from the individual analyzes, 20 patients, that is, approximately 13.42% had strains sensitive to all the medications indicated, with the others showing resistance to at least one of them. Conclusion: Based on the premise of efficacy performed by the empirical medication protocol established by the institution regarding the treatment of urinary tract infection in pregnant women, Cephalothin should certainly not be included in the list of drugs offered to patients. This happens because the sensitivity presented by Escherichia coli, the most commonly pathogen associated with the UTI pathogen of the service, to this drug is very low. Nitrofurantoin, on the other hand, presented a satisfactory coverage spectrum, with drug resistance below 10%. Thus, it is concluded that this should remain as an initial drug for ITUs of pregnant women who arrive at this institution.(AU)

A 28-Year-Old Pregnant Woman With a Lung Abscess and Complicated Pleural Effusion.

CASE PRESENTATION: A 28-year-old woman G1P0 at 22 weeks of gestation and with no significant medical history presented to the ED complaining of worsening dyspnea and right-sided pleuritic chest pain. Symptoms started 2 weeks before presentation, with minimal productive cough and dyspnea on exertion. One week after the initial symptoms, the patient started noticing right-sided chest and shoulder pain along with subjective fevers and night sweats. She denied hemoptysis, weight loss, abdominal pain, diarrhea, nausea, vomiting, arthralgia, or rash. Her pregnancy had so far been uncomplicated. The patient did not use tobacco, alcohol, or recreational drugs. She worked at a daycare center but denied any particular sick contacts. She moved to the United States 7 years ago from Sudan and denied any recent travel.

Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life.

BACKGROUND AND AIM: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum (WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring. METHODS AND RESULTS: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receiving L. plantarum WJL during pregnancy and lactation (DLP-LpWJL). L. plantarum WJL (1 × 109 CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-LpWJL dams had reduced blood pressure and recovered vascular function in later life. CONCLUSION: Administration of L. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.

Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes.

The purpose of this study was to explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy. In this study, oral and intestinal microbial composition was surveyed by using the 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features by using the quantitative real-time PCR (qPCR) approach in 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes. The 16S rRNA results showed that the relative abundances of Gammaproteobacteria were higher in pregnant women in the hypothyroidism group than in those in the control group, whereas the levels of Firmicutes were higher in the control group than in the hypothyroidism group. The serum C-reactive protein level, the weight gain during pregnancy, and the incidence of fetal distress were higher in the hypothyroidism group than in the control group. The QPCR results also showed the same changes of the intestinal microbiota in the two groups. There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.

The maternal microbiome modulates fetal neurodevelopment in mice.

'Dysbiosis' of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly associated with abnormalities in brain function and behaviour of the offspring4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during critical prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small molecules in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioural tasks, but no overt differences in many other sensorimotor behaviours. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.