Exploring the effect of prenatal maternal stress on the microbiomes of mothers and infants: A systematic review.

Prenatal maternal stress (PNMS)-characterized by exposure to stress, anxiety, depression, or intimate partner violence-has been linked to biological alterations in infants, including disruptions to their intestinal microbiota, which have long-term implications for children's developmental outcomes. Significant research has been done examining the effects of PNMS on the microbiome in animals, but less is known about these effects in human research. The current systematic review aimed to synthesize current findings on the association between PNMS and mother and infant microbiomes. Medline, Embase, PsycInfo, Web of Science, and Eric databases were searched through to February 2022. A total of eight studies (n = 2219 infants, 2202 mothers) were included in the qualitative synthesis. Findings provided promising evidence of the role that PNMS plays in altering the microbial composition, diversity, and gut immunity in mothers and infants. Notably, majority of included studies found that higher PNMS was linked to increases in genera from the phylum Proteobacteria. The factors influencing these effects are explored including nutrition, birth mode, and parenting behaviors. Potential interventions to mitigate the adverse effects of PNMS are discussed, along with recommendations for future studies with longitudinal designs to better understand the appropriate type and timing of interventions needed to promote "healthy" maternal and infant microbial functioning.

Do Maternal Microbes Shape Newborn Oral Microbes?

Strong evidence suggests that the early composition of the oral microbiota of neonates plays an important role for the postnatal development of the oral health or immune system. However, the relationship between the maternal microbiome and the initial neonatal microbiome remains unclear. In this study, 25 pregnant women and their neonates were recruited, and the samples were collected from the maternal oral cavity, amniotic fluid, placenta and neonatal oral cavity. High-throughput sequencing of 16S rRNA was performed using the Illumina MiSeq platform to analyze the correlation with microbial community structure between the maternal and the neonatal oral cavity. The results indicated that the number of shared OTUs was up to 635 in four groups. The PCoA showed that there were certain similarities in the microbial community structure of the four groups. The dominant bacterial genera of the shared OTUs were consistent with human oral microbes, including Streptococcus, Fusobacterium and Prevotella. The results showed that there might be a correlation between the maternal and neonatal oral microbiome, through the amniotic fluid and placenta.

The association between the maternal diet and the maternal and infant gut microbiome: a systematic review.

During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.

[The role of maternal imunity and woman´s microbiome in the pathogenesis of preterm labor]. / Úloha materské imunity a mikrobiomu zeny v patogenezi predcasného porodu.

OBJECTIVE: To summarize available data concerning the role of maternal imunity and woman´s microbiome in the pathogenesis of preterm labor and their use in clinical practice. SETTING: Department of Obstetrics and Gynecology od the First Faculty of Medicine, Charles University in Prague, and General Teaching Hospital. DESIGN: Review article. METHODS: Compilation od published data from scientific literature. CONCLUSION: Preterm labor complicates approximately 10% of all pregnancies and represents a serious medical, social and economic problem. In the past, a lot of causes of preterm labor were discussed; infection, uteroplacental ischemia, decidual hemorrhage, uterine overdistension, cervical disease and maternal-fetal tolerance disorder were considered the most common. However, chronic inflammation seems to be the common pathogenic process underlying preterm labor, irrespective of the original stimulus. Currently, impaired maternal-fetal immunological tolerance represents most discussed topic. Growing scientific evidence suggests that the immune regulation of the maternal-fetal interface is the result of the coordinated interaction among maternal microbiota, trophoblast and maternal cellular components. From this view we understand preterm labor as a result of disruption of this process.

Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy.

Background: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development. Importantly, although the fecal and vaginal microenvironments undergo alterations across pregnancy, we lack consensus regarding which shifts are adaptive or maladaptive in the presence of prenatal stress and depression. Clinical studies interrogating these relationships have identified unique taxa but have been limited in study design. Methods: We conducted a prospective cohort study of pregnant individuals consisting of repeated administration of psychometrics (Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D)) and collection of fecal and vaginal microbiome samples. Fecal and vaginal microbial community composition across psychometric responses were interrogated using full-length 16S rRNA sequencing followed by α and ß-diversity metrics and taxonomic abundance. Results: Early pregnancy stress was associated with increased abundance of fecal taxa not previously identified in related studies, and stress from late pregnancy through postpartum was associated with increased abundance of typical vaginal taxa and opportunistic pathogens in the fecal microenvironment. Additionally, in late pregnancy, maternal stress and depression scores were associated with each other and with elevated maternal C-C motif chemokine ligand 2 (CCL2) concentrations. At delivery, concordant with previous literature, umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal Lactobacilli. Lastly, participants with more severe depressive symptoms experienced steeper decreases in prenatal vaginal α-diversity. Conclusion: These findings a) underscore previous preclinical and clinical research demonstrating the effects of prenatal stress on maternal microbiome composition, b) suggest distinct biological pathways for the consequences of stress versus depression and c) extend the literature by identifying several taxa which may serve critical roles in mediating this relationship. Thus, further interrogation of the role of specific maternal microbial taxa in relation to psychosocial stress and its sequelae is warranted.

Gestational diabetes mellitus: Impacts on fetal neurodevelopment, gut dysbiosis, and the promise of precision medicine.

Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting approximately 16.5% of pregnancies worldwide and causing significant health concerns. GDM is a serious pregnancy complication caused by chronic insulin resistance in the mother and has been associated with the development of neurodevelopmental disorders in offspring. Emerging data support the notion that GDM affects both the maternal and fetal microbiome, altering the composition and function of the gut microbiota, resulting in dysbiosis. The observed dysregulation of microbial presence in GDM pregnancies has been connected to fetal neurodevelopmental problems. Several reviews have focused on the intricate development of maternal dysbiosis affecting the fetal microbiome. Omics data have been instrumental in deciphering the underlying relationship among GDM, gut dysbiosis, and fetal neurodevelopment, paving the way for precision medicine. Microbiome-associated omics analyses help elucidate how dysbiosis contributes to metabolic disturbances and inflammation, linking microbial changes to adverse pregnancy outcomes such as those seen in GDM. Integrating omics data across these different layers-genomics, transcriptomics, proteomics, metabolomics, and microbiomics-offers a comprehensive view of the molecular landscape underlying GDM. This review outlines the affected pathways and proposes future developments and possible personalized therapeutic interventions by integrating omics data on the maternal microbiome, genetics, lifestyle factors, and other relevant biomarkers aimed at identifying women at high risk of developing GDM. For example, machine learning tools have emerged with powerful capabilities to extract meaningful insights from large datasets.

The contribution of age-related changes in the gut-brain axis to neurological disorders.

Trillions of microbes live symbiotically in the host, specifically in mucosal tissues such as the gut. Recent advances in metagenomics and metabolomics have revealed that the gut microbiota plays a critical role in the regulation of host immunity and metabolism, communicating through bidirectional interactions in the microbiota-gut-brain axis (MGBA). The gut microbiota regulates both gut and systemic immunity and contributes to the neurodevelopment and behaviors of the host. With aging, the composition of the microbiota changes, and emerging studies have linked these shifts in microbial populations to age-related neurological diseases (NDs). Preclinical studies have demonstrated that gut microbiota-targeted therapies can improve behavioral outcomes in the host by modulating microbial, metabolomic, and immunological profiles. In this review, we discuss the pathways of brain-to-gut or gut-to-brain signaling and summarize the role of gut microbiota and microbial metabolites across the lifespan and in disease. We highlight recent studies investigating 1) microbial changes with aging; 2) how aging of the maternal microbiome can affect offspring health; and 3) the contribution of the microbiome to both chronic age-related diseases (e.g., Parkinson's disease, Alzheimer's disease and cerebral amyloidosis), and acute brain injury, including ischemic stroke and traumatic brain injury.

A Higher Abundance of Actinomyces spp. in the Gut Is Associated with Spontaneous Preterm Birth.

Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24-28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.

Influence of Maternal Breast Milk and Vaginal Microbiome on Neonatal Gut Microbiome: a Longitudinal Study during the First Year.

It is believed that establishment of the gut microbiome starts very early in life and is crucial for growth, immunity, and long-term metabolic health. In this longitudinal study, we recruited 25 mothers in their third trimester, of whom 15 had vaginal delivery while 10 had an unplanned cesarean section (C-section). The mother-neonate pairs were followed for 1 year, and we generated 16S metagenomic data to study the neonatal gut microbiome along with mother's breast milk and vaginal microbiomes through 12 months after delivery, at 1, 3, 6, and 12 months. We inferred (i) mode of delivery is an important factor influencing both composition and entropy of the neonatal gut microbiome, and the genus Streptococcus plays an important role in the temporal differentiation. (ii) Microbial diversity monotonically increases with age, irrespective of the mode of delivery, and it is significantly altered once exclusive breastfeeding is stopped. (iii) We found little evidence in favor of the microflora of mother's breast milk and a vaginal swab being directly reflected in the offspring's gut microbiome; however, some distinction could be made in the gut microbiome of neonates whose mothers were classified as community state type III (CSTIII) and CSTIV, based on their vaginal microbiomes. (iv) A lot of the mature gut microbiome is possibly acquired from the environment, as the genera Prevotella and Faecalibacterium, two of the most abundant flora in the neonatal gut microbiome, are introduced after initiation of solidified food. The distinction between the gut microbiome of babies born by vaginal delivery and babies born by C-section becomes blurred after introduction of solid food, although the diversity in the gut microbiota drastically increases in both cases. IMPORTANCE Gut microbiome architecture seems to have a potential impact on host metabolism, health, and nutrition. Early life gut microbiome development is considered a crucial phenomenon for neonatal health as well as adulthood metabolic complications. In this longitudinal study, we examined the association of neonatal gut microbiome entropy and its temporal variation. The study revealed that adult-like gut microbiome architecture starts taking shape after initiation of solidified food. Further, we also observed that the difference of microbial diversity was reduced between vaginally delivered and C-section babies compared to exclusive breastfeeding tenure. We found evidence in favor of the inheritance of the microflora of mother's posterior vaginal wall to the offspring's gut microbiome.

A Review Focusing on Microbial Vertical Transmission during Sow Pregnancy.

Microorganisms are closely related to the body's physiological activities and growth and development of the body, and participate in many physiological metabolic activities. Analysis of the structure and source of early colonizing bacteria in the intestinal tract of humans and rodents shows that early colonizing bacteria in the intestinal tract of mammals have solid maternal characteristics, and maternal microbes play an essential role in the formation of progeny intestinal flora. The placental microbiome, maternal microbiome and breast milk microbiome are currently hot topics in the field of life science. This paper discusses the vertical transmission and endogenous sources of the mother-to-piglet microbiome through these three pathways, aiming to provide a new research idea for intervention in the intestinal microbiome in young piglets.

Maternal microbiome disturbance induces deficits in the offspring's behaviors: a systematic review and meta-analysis.

Recent evidence has suggested that changes in maternal gut microbiota in early life may generate neurobiological consequences associated with psychiatric-related abnormalities. However, the number of studies on humans investigating this problem is limited, and preclinical findings sometimes conflict. Therefore, we run a meta-analysis to examine whether maternal microbiota disturbance (MMD) during neurodevelopment might affect the offspring during adulthood. We found thirteen studies, from a set of 459 records selected by strategy registered on PROSPERO (#289224), to target preclinical studies that evaluated the behavioral outcomes of the rodents generated by dams submitted to perinatal enteric microbiota perturbation. The analysis revealed a significant effect size (SMD = -0.51, 95% CI = -0.79 to -0.22, p < .001, T2 = 0.54, I2 = 79.85%), indicating that MMD might provoke behavioral impairments in the adult offspring. The MMD also induces a significant effect size for the reduction of the sociability behavior (SMD = -0.63, 95% CI = -1.18 to -0.07, p = 0.011, T2 = 0.30, I2 = 76.11%) and obsessive-compulsive-like behavior (SMD = -0.68, 95% CI = -0.01 to -1.36, p = 0.009, T2 = 0.25, I2 = 62.82%) parameters. The effect size was not significant or inconclusive for memory and anxiety-like behavior, or inconclusive for schizophrenia-like and depressive-like behavior. Therefore, experimental perinatal MMD is vertically transmitted to the offspring, negatively impacting behavioral parameters related to psychiatric disorders.

The Maternal Microbiome and Gestational Diabetes Mellitus: Cause and Effect.

Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.

From Mother to Infant, from Placenta to Gut: Understanding Varied Microbiome Profiles in Neonates.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, prompting the development of new frameworks through epidemiological studies. Traditionally, it was believed that each individual harbored unique microbial communities acquired early in life, evolving over the course of their lifetime, with little acknowledgment of any prenatal microbial development, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

The influence of maternal factors on the neonatal microbiome and health.

The human microbiome plays an essential role in human health. However, the influence of maternal factors on the neonatal microbiome remains obscure. Herein, our observations suggest that the neonatal buccal microbiome is similar to the maternal buccal microbiome, but the neonatal gastrointestinal microbiome develops a unique composition at an early stage. The low complexity of the neonatal buccal microbiome is a hallmark of maternal and neonatal health, but that of the neonatal gastrointestinal microbiome is associated with maternal inflammation-related metabolites. Microbial infections in the maternal reproductive tract universally impact the complexity of the neonatal microbiomes, and the body site is most important in modulating the composition of the neonatal microbiomes. Additionally, maternal lipids attenuated the adverse influence of several maternal factors on the neonatal microbiomes. Finally, admission of neonates to the newborn intensive care unit is associated with sub-optimal states of the maternal buccal and rectal microbiomes and maternal health.

Maternal transmission of bacterial microbiota during embryonic development in a viviparous lizard.

IMPORTANCE: We investigated the presence and diversity of bacteria in the embryos of the viviparous lizard Sceloporus grammicus and their amniotic environment. We compared this diversity to that found in the maternal intestine, mouth, and cloaca. We detected bacterial DNA in the embryos, albeit with a lower bacterial species diversity than found in maternal tissues. Most of the bacterial species detected in the embryos were also found in the mother, although not all of them. Interestingly, we detected a high similarity in the composition of bacterial species among embryos from different mothers. These findings suggest that there may be a mechanism controlling the transmission of bacteria from the mother to the embryo. Our results highlight the possibility that the interaction between maternal bacteria and the embryo may affect the development of the lizards.

Intersections of the microbiome and early neurodevelopment.

Our resident microbes influence nearly all aspects of our biological systems. In particular, the maternal and early life microbiota is uniquely positioned to influence the development of the nervous system, and alterations to the gut microbiota, or dysbiosis, during this critical time in early life can have long-lasting negative effects on health. The question of how the maternal and early life microbiota shapes neurodevelopment is the topic of numerous investigations. Here, we discuss two possible, but not necessarily independent, hypotheses: (1) the maternal microbiota during pregnancy regulates the metabolites that are important for fetal development, (2) maternal microbiota seeded to offspring at birth and early postnatal days programs offspring immune and brain development, and regulates key molecules for postnatal brain development. In this chapter, we provide an overview of the impact of the microbiota on brain and behavior, introduce the maternal gut and vaginal microbiome during pregnancy, and discuss current understandings of microbiome in the context of developmental origins of health and disease. We consider novel translational insights that harness the multitude of microbes and microbial metabolites for prevention or treatment of neurological disorders.

The dynamic communities of oral microbiome in neonates.

The oral microbiome, associated with both oral disease and systemic disease, is in dynamic status along the whole life, and many factors including maternal microbiomes could impact the oral microbiome. While fewer studies have been conducted to study the characteristics of the oral microbiome in neonates and the associated maternal factors. Hence, we collected the microbiome of 15 mother-infant pairs across multiple body sites from birth up to 4 days postpartum and used high-throughput sequencing to characterize the microbiomes in mothers and their neonates. The oral microbiome in the neonates changed obviously during the 4 days after birth. Many bacteria originating from the vagina, skin, and environment disappeared in oral cavity over time, such as Prevotella bivia and Prevotella jejuni. Meanwhile, Staphylococcus epidermidis RP62A phage SP-beta, predominate bacterium in maternal skin microbiome and Streptococcus unclassified, main bacterium in vaginal microbiome, obviously increased in neonatal oral microbiome as time went on. Interestingly, as time progressed, the composition of the oral microbiome in the neonates was more similar to that of the milk microbiome in their mothers. Moreover, we found that the changes in the predominant bacteria in the neonates were in line with those in the neonates exposed to the environment. Together, these data described the sharp dynamics of the oral microbiome in neonates and the importance of maternal efforts in the development of the neonatal microbiome.

C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [clostridium] scindens in mice.

In humans and animal models, Cesarean section (C-section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C-section effects are context-specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 week old mice born by C-section (n = 16) versus natural birth (n = 23) were compared under matched conditions for housing, cross-fostering, diet, sex, and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray-Curtis dissimilarities and Aitchison distances (using log[x + 1]-transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C-section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that C-section does not inherently lead to large-scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context-specific manner: For example, involving factors associated with pre-, peri-, and postpartum environments, diet or host genetics.

Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction.

To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses' whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.

The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine.

The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m6A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m6A modification of the host, it remains unclear whether the maternal microbiome affects m6A epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of m6A writers and erasers, as well as the m6A methylome of the mouse fetal brain and intestine on embryonic day 18. From the m6A profiles, we identified 2,655 and 2,252 m6A modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these m6A-modified genes were enriched in the neuro/intestinal developmental pathways, such as the Wnt signaling pathway. Finally, we verified that antibiotic treatment mostly recapitulated changes in m6A, and we further showed that the loss of heterozygosity of Mettl3 rescued m6A levels and the expression changes of some developmental genes in the fetal intestine that resulted from antibiotic treatment. Collectively, our data revealed that the maternal microbiome programs the m6A epitranscriptome of the mouse fetal brain and intestine.