Maternal Microbiome Research Articles

Microbiome analysis of serum extracellular vesicles in gestational diabetes patients.

Gestational Diabetes Mellitus (GDM) is among the most common complications during pregnancy, posing serious risks to both the patient's and offspring's health and well-being. Alterations in the maternal microbiome are closely associated with the pathogenesis of GDM, with Extracellular Vesicles (EVs) facilitating communication between microbiota and the host. However, little is known about the relationship between the microbial composition within EVs and the pathogenesis of GDM. Therefore, this study aims to characterize the microbiota within serum EVs of GDM Patients (GDM group) and to identify microbial communities that significantly differ from those in Women With Normal Pregnancies (NonGDM group). Blood samples were collected from both groups of patients, and EVs derived from serum were isolated via centrifugation. Identification and characterization of EVs were performed using transmission electron microscopy and nanoparticle flow cytometry. Microbiome analysis of serum EVs from both groups was conducted using 16S rRNA sequencing. Results indicated altered diversity in microbial communities within serum EVs of GDM patients. Further analysis at the phylum, family, genus, and species levels revealed that Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the dominant taxa in the EVs of both the NonGDM and GDM groups. Specifically, Actinobacteria and Firmicutes showed increased relative abundance in GDM group EVs compared to NonGDM, leading to a higher Firmicutes/Bacteroidetes ratio, while Proteobacteria and Bacteroidetes exhibited decreased relative abundance. Tax4Fun analysis revealed enrichment of microbial functions related to amino acid metabolism, carbohydrate metabolism, energy metabolism, and metabolism of cofactors and vitamins in both patient groups. In conclusion, this study reveals a potential correlation between changes in the microbial composition and diversity of serum EVs and the onset and development of GDM. Furthermore, changes in the relative abundance of Actinobacteria, Proteobacteria,Bacteroidetes, and Firmicutes may play an important role in the pathogenesis of GDM.

Maternal high fat diet exposure modifies amniotic fluid metabolites and expands group 3 innate lymphoid cells dependent on the maternal microbiome and MyD88-signaling

BackgroundMaternal high fat diet (mHFD) exposure expands IL-17 producing group 3 innate lymphoid cells (IL17+ve ILC3) in the small intestine of neonatal murine offspring and increases their susceptibility to intestinal inflammation. How mHFD modulates innate immunity in the fetal offspring remains unclear.MethodsDams were exposed to 60% high fat diet or maintained on regular diet (RD) prior to and during mating. Amniotic fluid (AF) was collected during mid-pregnancy and metabolites examined by global non-targeted mass spectrometry in conventional wild-type (WT) and germ-free pregnant dams. Offspring were delivered by C-section or vaginally and fecal contents examined for major bacterial phyla and small intestinal lamina propria cells (LP) by flow cytometry. Susceptibility to intestinal inflammation was determined using a lipopolysaccharide and platelet-activating factor model (LPS/PAF) in WT, germ-free and MyD88 deficient offspring. Neonatal germ-free pups were exposed to HFD or RD AF by gavage and LP examined by flow cytometry.ResultsWe identified differentially produced metabolites in mHFD AF when compared to RD AF in conventionally raised mice, with no difference seen in germ-free mice. C-section delivery maintained the mHFD phenotype of expansion of IL17+ve ILC3 and increased susceptibility to inflammation in neonatal offspring. In addition, mHFD offspring had expansion of IL17+ve ILC3 at birth and 2 weeks of life, which was not seen in germ-free and MyD88 KO mice exposed to mHFD. Germ-free and MyD88 KO mice were protected from mHFD induced LPS/PAF injury and IL17+ve ILC3 expansion, demonstrating that the maternal microbiome and MyD88 are prenatally necessary for the expansion of IL17+ve ILC3 in mHFD offspring. Furthermore, introduction of mHFD AF to neonatal germ-free pups by gavage was sufficient to expand IL17+ve ILC3 in the small intestine.ConclusionOur findings indicate that mHFD interacts with the maternal microbiome to modify AF metabolites and signal via MyD88 to expand IL17+ve ILC3 in murine neonatal offspring.

Nutraceuticals as Modulators of Molecular Placental Pathways: Their Potential to Prevent and Support the Treatment of Preeclampsia

Preeclampsia (PE) is a serious condition characterized by new-onset hypertension and proteinuria or organ dysfunction after the 20th week of gestation, making it a leading cause of maternal and fetal mortality worldwide. Despite extensive research, significant gaps remain in understanding the mechanisms underlying PE, contributing to the ineffectiveness of current prevention and treatment strategies. Consequently, premature cesarean sections often become the primary intervention to safeguard maternal and fetal health. Emerging evidence indicates that placental insufficiency, driven by molecular disturbances, plays a central role in the development of PE. Additionally, the maternal microbiome may be implicated in the pathomechanism of preeclampsia by secreting metabolites that influence maternal inflammation and oxidative stress, thereby affecting placental health. Given the limitations of pharmaceuticals during pregnancy due to potential risks to fetal development and concerns about teratogenic effects, nutraceuticals may provide safer alternatives. Nutraceuticals are food products or dietary supplements that offer health benefits beyond basic nutrition, including plant extracts or probiotics. Their historical use in traditional medicine has provided valuable insights into their safety and efficacy, including for pregnant women. This review will examine how the adoption of nutraceuticals can enhance dysregulated placental pathways, potentially offering benefits in the prevention and treatment of preeclampsia.

Association of Neonatal and Maternal Nasal Microbiome Among Neonates in the Intensive Care Unit.

The neonatal nasal microbiota may help protect neonates in the neonatal intensive care unit from pathogen colonization and infection. This preliminary study characterized the biodiversity of nasal microbiota comparing neonates in the neonatal intensive care unit and their mothers, highlighting the potential of strain sharing between mother-neonate pairs.

Maternal dysbiosis produces long-lasting behavioral changes in offspring.

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization of young dams with microbiome from aged female donors significantly increased fetal loss. There were significant differences in the composition of the gut microbiome in pups born from dams recolonized with aged female biome that persisted through middle age. Offspring born from dams colonized with aged microbiome also had significant changes in levels of neurotransmitters and metabolites in the blood and the brain. Adult offspring from dams colonized with an aged microbiome displayed persistent depressive- and anxiety-like phenotypes. Collectively, these results demonstrate that age-related changes in the composition of the maternal gut microbiome contribute to chronic alterations in the behavior and physiology of offspring. This work highlights the potential of microbiome-targeted approaches, even prior to birth, may reduce the risk of neuropsychiatric disorders.

Fetal programming by the parental microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus.

The microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as the gut microbiome, affect numerous host behaviors dependent on the central nervous system (CNS). Studies comparing germ-free mice to normally colonized mice have demonstrated influences of the microbiome on anxiety-related behaviors, voluntary activity, and gene expression in the CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence of the maternal microbiome on neurodevelopment of offspring and behavior later in life. There is limited experimental evidence however directly linking the maternal microbiome to long-term neurodevelopmental outcomes, or knowledge regarding mechanisms responsible for such effects. Here we show that that the maternal microbiome has a dominant influence on several offspring phenotypes including anxiety-related behavior, voluntary activity, and body weight. Adverse outcomes in offspring were associated with features of the maternal microbiome including bile salt hydrolase activity gene expression ( bsh ), abundance of certain bile acids, and hepatic expression of Slc10a1 . In cross-foster experiments, offspring resembled their birth dam phenotypically, despite faithful colonization in the postnatal period with the surrogate dam microbiome. Genome-wide methylation analysis of hippocampal DNA identified microbiome- associated differences in methylation of 196 loci in total, 176 of which show conserved profiles between mother and offspring. Further, single-cell transcriptional analysis revealed accompanying differences in expression of several differentially methylated genes within certain hippocampal cell clusters, and vascular expression of genes associated with bile acid transport. Inferred cell-to-cell communication in the hippocampus based on coordinated ligand-receptor expression revealed differences in expression of neuropeptides associated with satiety. Collectively, these data provide proof-of-principle that the maternal gut microbiome has a dominant influence on the neurodevelopment underlying certain offspring behaviors and activities, and selectively affects genome methylation and gene expression in the offspring CNS in conjunction with that neurodevelopment.

Maternal gastrointestinal microbiome shapes gut microbial function and resistome of newborns in a cow-to-calf model

BackgroundThe maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring.ResultsThe microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly.ConclusionsOur study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome.2cueHjjtpyRzwmAWUdZ5oAVideo

Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from the Women First Trial.

Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings. This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine. No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance. Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.

MICROBIOME: The trials and errors of developing an experimental model to study the impact of maternal gut microbiome disruption on perinatal asphyxia.

Maternal gut microbiome impairment has garnered attention for its potential role in influencing neurodevelopmental outcomes in offspring, especially in situations that increase brain vulnerability such as perinatal asphyxia (PA). Maternal microbiome and fetal brain interplay emerge as a critical link between maternal health and offspring neurodevelopment. This study aims to generate a model to assess the impact of maternal dysbiosis triggered by gestational antibiotic administration and PA on offspring neurodevelopment. Wistar rats were subjected to antibiotics in drinking water from the 11th gestational day until birth. On the 6th postnatal day, pups were subjected to PA/normoxia, resulting in four experimental groups: control-normoxia, antibiotics-normoxia, control-asphyxia, and antibiotics-asphyxia. Early-life behavioral tests were conducted between postnatal days 7 and 9. The initial antimicrobial cocktail (ampicillin, vancomycin, neomycin, clindamycin, amphotericin-B) led to an increased number of miscarriages, poor weight gain during pregnancy, reduced offspring weight, and changes in the maternal gut microbiome compared to control. Offspring presented impaired neurodevelopmental reflexes in both PA and antibiotic groups and increased hippocampal neuroinflammation. Due to these detrimental effects, a more pregnancy-safe antibiotic cocktail was used for a second experiment (ampicillin, vancomycin, neomycin, meropenem). This resulted in no miscarriages or pregnancy-weight loss but was still linked to gut microbiome disruption. PA impaired neurodevelopmental reflexes and increased neuroinflammation, effects amplified by antibiotic administration. These preliminary findings reveal the cumulative potential of maternal dysbiosis and PA on neurodevelopment impairment, emphasizing caution in gestational antimicrobial use. Further investigations should include offspring long-term follow-up and maternal behavior and integrate probiotics to counteract antibiotic effects. This study investigates the impact of maternal gut microbiome disruptions caused by gestational antibiotic treatment and low oxygen exposure shortly after birth on the development of the rats' babies. We found that both antibiotic exposure and reduced oxygen levels led to changes in early behavior and increased inflammation of the nervous tissue in the baby rats. Although using a different, potentially safer antibiotic combination reduced pregnancy complications, it still changed the bacteria in the mother's gut and worsened early behavior. These findings show that antibiotics during pregnancy can affect the developing brain of baby rats and careful consideration should be used before prescribing them. Future research will explore longer-term effects and potential medicines.

Relationship between infant gastrointestinal microorganisms and maternal microbiome within 6 months of delivery.

To investigate the association between the microbiota in mothers and gut microbiota in infants from 0 to 6 months, the microbiotas in infant feces, maternal feces, and breast milk were determined by 16S rRNA gene sequencing. The contribution of each maternal microbiome to the infant was assessed using fast expectation-maximization for microbial source tracking calculations. The levels of short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA) in the feces of infants were also determined using gas chromatography and IDK-sIgA ELISA to gain a more comprehensive understanding of the infant gut microbiome. The results of this study showed that in addition to Firmicutes (E1) and Bifidobacterium (E2), the dominant microorganisms of the intestinal microbiota of infants aged 0-6 months include Proteobacteria, which is different from previous findings. Acetic acid, the most abundant SCFA in the infant gut, was positively correlated with Megasphaera (P < 0.01), whereas sIgA was positively correlated with Bacteroides (P < 0.05) and negatively correlated with Klebsiella and Clostridium_XVIII (P < 0.05). The maternal gut microbiota contributed more to the infant gut microbiota (43.58% ± 11.13%) than the breast milk microbiota, and significant differences were observed in the contribution of the maternal microbiota to the infant gut microbiota based on the delivery mode and feeding practices. In summary, we emphasize the key role of maternal gut health in the establishment and succession of infant gut microbiota.IMPORTANCEThis study aims to delineate the microbial connections between mothers and infants, leveraging the fast expectation-maximization for microbial source tracking methodology to quantify the contribution of maternal microbiota to the constitution of the infant's gut microbiome. Concurrently, it examines the correlations between the infant gut microbiota and two distinctive biomolecules, namely short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA). The findings indicate that the maternal gut microbiota exerts a greater influence on the infant's gut microbial composition than does the microbiota present in breast milk. Infants born via vaginal delivery and receiving mixed feeding display gut microbiota profiles more similar to their mothers'. Notably, the SCFA acetate displays positive associations with beneficial bacteria and inverse relationships with potentially harmful ones within the infant's gut. Meanwhile, sIgA positively correlates with Bacteroides species and negatively with potentially pathogenic bacteria. By delving into the transmission dynamics of maternal-infant microbiota, exploring the impacts of metabolic byproducts within the infant's gut, and scrutinizing how contextual factors such as birthing method and feeding practices affect the correlation between maternal and infant microbiota, this research endeavors to establish practical strategies for optimizing early-life gut health management in infants. Such insights promise to inform targeted interventions that foster healthier microbial development during the critical first 6 months of life.

Maternal oral probiotic use is associated with decreased breastmilk inflammatory markers, infant fecal microbiome variation, and altered recognition memory responses in infants-a pilot observational study.

Early life gut microbiomes are important for brain and immune system development in animal models. Probiotic use has been proposed as a strategy to promote health via modulation of microbiomes. In this observational study, we explore if early life exposure to probiotics via the mother during pregnancy and lactation, is associated with decreased inflammation in breastmilk, maternal and infant microbiome variation, and altered infant neurodevelopmental features. Exclusively breastfeeding mother-infant dyads were recruited as part of the "Mothers and Infants Linked for Healthy Growth (MILk) Study." Probiotic comparison groups were defined by exposure to maternal probiotics (NO/YES) and by timing of probiotic exposure (prenatal, postnatal, total). C-reactive protein (CRP) and IL-6 levels were determined in breastmilk by immunoassays, and microbiomes were characterized from 1-month milk and from 1- and 6-month infant feces by 16S rDNA sequencing. Infant brain function was profiled via electroencephalogram (EEG); we assessed recognition memory using event-related potential (ERP) responses to familiar and novel auditory (1 month) and visual (6 months) stimuli. Statistical comparisons of study outcomes between probiotic groups were performed using permutational analysis of variance (PERMANOVA) (microbiome) and linear models (all other study outcomes), including relevant covariables as indicated. We observed associations between probiotic exposure and lower breastmilk CRP and IL-6 levels, and infant gut microbiome variation at 1- and 6-months of age (including higher abundances of Bifidobacteria and Lactobacillus). In addition, maternal probiotic exposure was associated with differences in infant ERP features at 6-months of age. Specifically, infants who were exposed to postnatal maternal probiotics (between the 1- and 6-month study visits) via breastfeeding/breastmilk, had larger differential responses between familiar and novel visual stimuli with respect to the late slow wave component of the EEG, which may indicate greater memory updating potential. The milk of mothers of this subgroup of infants had lower IL-6 levels and infants had different 6-month fecal microbiomes as compared to those in the "NO" maternal probiotics group. These results support continued research into "Microbiota-Gut-Brain" connections during early life and the role of pre- and postnatal probiotics in mothers to promote healthy microbiome-associated outcomes in infants.

Dietary Sugar and Saturated Fat Consumption Associated with the Gastrointestinal Microbiome during Pregnancy

BackgroundGrowing evidence supports changes in the gastrointestinal microbiome over the course of pregnancy may have an impact on the short- and long-term health of both the mother and the child. ObjectiveOur objective was to explore the association of diet quality, as measured by the Healthy Eating Index (HEI), with the composition and gene ontology (GO) representation of microbial function in the maternal gastrointestinal microbiome during pregnancy. MethodsWe conducted a retrospective, observational analysis of n = 185 pregnant participants in the Pregnancy Eating Attributes Study. Maternal dietary intake was assessed in the first trimester using the automated self-administered 24-h recall method, from which the HEI 2015 was calculated. Rectal swabs were obtained in the second trimester and sequenced using the NovaSeq 6000 system shotgun platform. We used unsupervised clustering to identify microbial enterotypes representative of maternal taxa and GO functional term composition. Multivariable linear models were used to identify associations between taxa, functional terms, and food components while controlling for relevant covariates. Multinomial regression was then used to predict enterotype membership based on a participant’s HEI food component score. ResultsThose in the high diet quality tertile had a lower early pregnancy BMI [mean (M) = 23.48 kg/m2, SD = 3.38] compared with the middle (M = 27.35, SD = 6.01) and low (M = 27.49, SD = 6.99) diet quality tertiles (P < 0.01). There were no statistically significant associations between the HEI components or the total HEI score and the 4 alpha diversity measures. Differences in taxa and GO term enterotypes were found in participants with, but not limited to, a higher saturated fat component score (β = 1.35, P = 0.01), added sugar HEI component (β = 0.07, P < 0.001), and higher total dairy score (β = 1.58, P = 0.01). ConclusionsSpecific dietary components are associated with microbial composition and function in the second trimester of pregnancy. These findings provide a foundation for future testable hypotheses.

Perinatal Exposure to Tobacco Smoke and Its Association with the Maternal and Offspring Microbiome: A Systematic Review.

The human microbiome, comprising trillions of microorganisms, significantly influences human health and disease. During critical periods like the perinatal phase, the microbiome undergoes significant changes, impacting lifelong health. Tobacco smoke, a known environmental pollutant, has adverse effects on health, particularly during pregnancy. Despite this, its association with the perinatal microbiome remains understudied. We conducted a systematic review to integrate findings on perinatal tobacco smoke exposure and its association with the maternal and neonatal microbiomes. We conducted a comprehensive literature search in the PubMed, Scopus, and Web of Science databases from January 2000 to February 2024. We selected studies that met predefined inclusion criteria and performed data extraction. The review included eight studies that revealed diverse associations of perinatal tobacco exposure with the maternal and neonatal microbiome. Active smoking during pregnancy was linked to alterations in microbiome composition and diversity in children. Maternal smoking correlated with increased Firmicutes abundance and decreased Akkermansia muciniphila abundance in offspring. Additionally, exposure to thirdhand smoke in neonatal intensive care units was related to infant microbiome diversity. Infants exposed to tobacco smoke showed various microbial changes, suggesting potential implications for childhood health outcomes, including obesity risk. Perinatal exposure to tobacco smoke exerts significant influence on the maternal and neonatal microbiomes, with potential implications for long-term health outcomes. Addressing socioeconomic and psychological barriers to smoking cessation, implementing stricter smoking regulations, and promoting public health campaigns are essential steps towards reducing tobacco-related harm during the perinatal period. Further longitudinal studies and standardized assessment methods are needed to validate these findings and guide the development of effective preventive measures.

Randomised control trial indicates micronutrient supplementation may support a more robust maternal microbiome for women with antenatal depression during pregnancy

Background and AimsWe investigated the effects of high dose dietary micronutrient supplementation or placebo on the human gut microbiome in pregnant women who had moderate symptoms of antenatal depression. There is a significant absence of well-controlled clinical studies that have investigated the dynamic changes of the microbiome during pregnancy and the relationship among diet, microbiome and antenatal depression. This research is among the first to provide an insight into this area of research. MethodsThis 12 - week study followed a standard double blinded randomised placebo-controlled trial (RCT) design with either high dose micronutrients or active placebo. Matching stool microbiome samples and mood data were obtained at baseline and post-treatment, from participants between 12 and 24 weeks gestation. Stool microbiome samples from 33 participants (17 in the placebo and 16 in the treatment group) were assessed using 16s rRNA sequencing. Data preparation and statistical analysis was predominantly performed using the QIIME2 bioinformatic software tools for 16s rRNA analysis. ResultsMicrobiome community structure became increasingly heterogenous with decreased diversity during the course of the study, which was represented by significant changes in alpha and beta diversity. This effect appeared to be mitigated by micronutrient administration. There were less substantial changes at the genus level, where Coprococcus decreased in relative abundance in response to micronutrient administration. We also observed that a higher abundance of Coprococcus and higher alpha diversity correlated with higher antenatal depression scores. ConclusionsMicronutrient treatment appeared to support a more diverse (alpha diversity) and stable (beta diversity) microbiome during pregnancy. This may aid in maintaining a more resilient or adaptable microbial community, which would help protect against decreases or fluctuations that are observed during pregnancy.

Birth and household exposures are associated with changes to skin bacterial communities during infancy

Abstract Microbial exposures during infancy shape the development of the microbiome, the collection of microbes living in and on the body, which in turn directs immune system training. Newborns acquire a substantial quantity of microbes during birth and throughout infancy via exposure to microbes in the physical and social environment. Alterations to early life microbial environments may give rise to mismatches, where environmental, cultural, and behavioral changes that outpace the body’s adaptive responses can lead to adverse health outcomes, particularly those related to microbiome development and immune system regulation. This study explored the development of the skin microbiome among infants born in Chicago, USA. We collected skin swab microbiome samples from 22 mother-infant dyads during the first 48 hours of life and again at six weeks postpartum. Mothers provided information about social environments and hygiene behaviors that may impact infants’ microbial exposures. Analysis of 16S rRNA bacterial gene sequencing data revealed correlations between infant skin bacterial abundance shortly after birth and factors such as antibiotic exposure and receiving a bath in the hospital. The composition of the infant microbiome at six weeks of age was associated with interactions with caregivers and infant feeding practices. We also found shifts in maternal skin microbiomes that may reflect increased hygiene practices in the hospital. Our data suggest that factors related to the birth and household environment can impact the development of infant skin microbiomes and point to practices that may produce mismatches for the infant microbiome and immune system.

Gestational Interrelationships among Gut-Metabolism-Transcriptome in Regulating Early Embryo Implantation and Placental Development in Mice.

Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile at E8 compared to controls, with the differential metabolites primarily enriched in amino acid metabolism pathways. The gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift in beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct genes between the E8 and control mice. The differentially expressed genes were enriched in pathways involved in alanine, aspartate, and glutamate metabolism, PI3K-Akt signaling, and the PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, the gut microbiome, and the uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development.

Depletion of the paternal gut microbiome alters sperm small RNAs and impacts offspring physiology and behavior in mice

The paternal environment prior to conception has been demonstrated to influence offspring physiology and behavior, with the sperm epigenome (including noncoding RNAs) proposed as a potential facilitator of non-genetic inheritance. Whilst the maternal gut microbiome has been established as an important influence on offspring development, the impact of the paternal gut microbiome on offspring development, health and behavior is largely unknown. Gut microbiota have major influences on immunity, and thus we hypothesized that they may be relevant to paternal immune activation (PIA) modulating epigenetic inheritance in mice. Therefore, male C57BL/6J mice (F0) were orally administered non-absorbable antibiotics via drinking water in order to substantially deplete their gut microbiome. Four weeks after administration of the antibiotics (gut microbiome depletion), F0 male mice were then mated with naïve female mice. The F1 offspring of the microbiome-depleted males had reduced body weight as well as altered gut morphology (shortened colon length). F1 females showed significant alterations in affective behaviors, including measures of anxiety and depressive-like behaviors, indicating altered development. Analysis of small noncoding RNAs in the sperm of F0 mice revealed that gut microbiome depletion is associated with differential expression of 8 different PIWI-interacting RNAs (piRNAs), each of which has the potential to modulate the expression of multiple downstream gene targets, and thus influence epigenetic inheritance and offspring development. This study demonstrates that the gut-germline axis influences sperm small RNA profiles and offspring physiology, with specific impacts on offspring affective and/or coping behaviors. These findings may have broader implications for other animal species with comparable gut microbiota, intergenerational epigenetics and developmental biology, including humans.

Prenatal Stress and Ethanol Exposure: Microbiota-Induced Immune Dysregulation and Psychiatric Risks.

Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring's health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and phrases related to maternal stress, ethanol exposure, gut microbiota, microbiome, gut-brain axis, diet, dysbiosis, progesterone, placenta, prenatal development, immunity, inflammation, and depression to identify relevant studies in both preclinical and human research. Only a limited number of reviews were included to support the arguments. The search encompassed studies from the 1990s to the present. This review begins by exploring the role of microbiota in modulating host health and disease. It then examines how disturbances in maternal microbiota can affect the offspring's immune system. The analysis continues by investigating the interplay between stress and dysbiosis, focusing on how prenatal maternal stress influences both maternal and offspring microbiota and its implications for susceptibility to depression. The review also considers the impact of ethanol consumption on gut dysbiosis, with an emphasis on the effects of prenatal ethanol exposure on both maternal and offspring microbiota. Finally, it is suggested that maternal gut microbiota dysbiosis may be significantly exacerbated by the combined effects of stress and ethanol exposure, leading to immune system dysfunction and chronic inflammation, which could increase the risk of depression in the offspring. These interactions underscore the potential for novel mental health interventions that address the gut-brain axis, especially in relation to maternal and offspring health.

Temporal Investigation of the Maternal Origins of Fetal Gut Microbiota.

In utero colonization or deposition of beneficial microorganisms and their by-products likely occurs through various mechanisms, such as hematogenous spread or ascension from the reproductive tract. With high-throughput sequencing techniques, the identification of microbial components in first-pass neonatal meconium has been achieved. While these components are low-biomass and often not abundant enough to culture, the presence of microbial DNA signatures may promote fetal immune tolerance or epigenetic regulation prior to birth. The aim of this study was to investigate the maternal source of the neonatal first-pass meconium microbiome. Maternal vaginal and anal samples collected from twenty-one maternal-infant dyad pairs were compared via principal component analysis to first-pass neonatal meconium microbial compositions. Results demonstrated the greatest degree of similarity between the maternal gut microbiome in the second and third trimesters and vaginal microbiome samples across pregnancy, suggesting that the maternal gut microbiota may translocate to the fetal gut during pregnancy. This study sheds light on the origin and timing of the potential transfer of maternal microbial species to offspring in utero.

Maternal immune cell gene expression associates with maternal gut microbiome, milk composition and infant gut microbiome

Background– Pre-pregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, the impact of pre-pregnancy overweight on immune cell gene expression during pregnancy and its association with maternal and infant outcomes is not well explored. Methods– Blood samples were collected from healthy normal weight (NW, pre-pregnancy BMI 18.5-24.9) or overweight (OW, pre-pregnancy BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. ResultsGene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions– These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Furthermore, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.