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ABSTRACTTrillions 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.

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.

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 β-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.

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. [ABSTRACT FROM AUTHOR]

ABSTRACT The maternal transmission of microbiota during embryonic development of vertebrates is still poorly understood. Here, we used high-throughput sequencing of the 16S rRNA bacterial genes to determine the bacterial communities in the gastrointestinal tract and amniotic environment, i.e., the amniotic fluid, amniotic membrane and extraembryonic yolk, of embryos at the last stage of development of the viviparous lizard Sceloporus grammicus Wiegmann, 1828. We compared these communities to those found in the maternal intestine, mouth, cloaca, and the aseptic ventral skin as a control of the aseptic technique. Our results showed that bacterial 16S rRNA genes were present in the embryos of S. grammicus. Their diversity was lower and more similar in composition between individuals than those found in the maternal tissues. This suggests that a strong control exists on the transmission of bacteria from the mother to the embryos. We found 78% of the embryonic amplicon sequence variants (ASVs) in the maternal bacterial microbiota, suggesting that the transmission of bacteria from the mother to the embryos is a continuous process and some bacteria may have been transferred during early embryonic stages. The embryonic bacteria were found to overlap mostly with those found in the mouth and aseptic ventral skin of the mother, although it is difficult to conclude that the shared ASVs originated from these maternal tissues. Our study provides evidence of microbiota vertical transfer during embryonic development in the animal kingdom. It also highlights that this maternal transmission could be included in the maternal effects that impact the offspring. 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT 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.

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 ribosomal RNA 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/d) and fibre (g/d) 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Simple Summary: Neonates are highly susceptible to intestinal infections; this has been generally ascribed to the immaturity of the immune system, but other factors might contribute. The composition of the gut microbiota is a key factor, as the microbiota protects the host against colonization by pathogens. The neonatal gut microbiota is less diverse and lacks two taxa that are dominant in older intestines: members of the orders Clostridiales and Bacteroidales. 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. 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. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE three-fold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short chain fatty acids (SCFA) compared to controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 compared to C57 controls was different using PERMANOVA with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared to controls. Alistipes and Helicobacter were increased while Bacteroides, Lactobacillus, Parasulterrella , and Parabacteroides were decreased compared to controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acid were decreased while isobutyric and isovaleric acid were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, GPR41 . In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype.

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.

The correlation between the maternal and neonatal microbiome helps to understand the mechanisms that govern the metabolic and immune processes of the newborn. The literature of recent years brings pros and cons regarding the role of the placenta as a microbial residence and its involvement secondary to microbial colonization in premature birth. Additional multi-omics research will be needed to establish the role of this transient organ in elucidating the processes that govern premature birth. DNA sequencing has made it possible to identify microbial species in the human microbiome. Thus, the role of the maternal microbiome in pregnancy and related complications are partially elucidated. This article aimed to identify the diversity of species in the maternal placental microbiome, the possible association with the newborn microbiome, and the influence of dysbiosis in spontaneous premature birth (PTB). In pregnancy, the changes in the microbiome are multifactorial, and the analysis performed demonstrating the continuous intervention of the body in order to adapt the intestinal microbiota to have a positive maternal-fetal result.

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.

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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.

Background: 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., Results: 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., Conclusions: 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., Competing Interests: Competing Interests The authors declare no competing interests.

Recent developments call for further research on the timing and mechanisms involved in the initial colonization of the fetal/infant gut by the maternal microbiome and its role in Developmental Origins of Health and Disease (DOHaD). Although progress has been made using primarily preterm infants, ethical and legal constraints hinder research progress in embryo/fetal-related research and understanding the developmental and mechanistic roles of the maternal microbiome in fetal microbial imprinting and its long-term role in early-life microbiome development. Rodent models have proven very good for studying the role of the maternal microbiome in fetal programming. However, some inherent limitations in these animal models make it challenging to study perinatal microbial colonization from a biomedical standpoint. In this review, we discuss the potential use of bovine animals as a biomedical model to study the maternal microbiome, in utero microbial colonization of the fetal gut, and their impact on offspring development and DOHaD.

Recent developments call for further research on the timing and mechanisms involved in the initial colonization of the fetal/infant gut by the maternal microbiome and its role in Developmental Origins of Health and Disease (DOHaD). Although progress has been made using primarily preterm infants, ethical and legal constraints hinder research progress in embryo/fetal-related research and understanding the developmental and mechanistic roles of the maternal microbiome in fetal microbial imprinting and its long-term role in early-life microbiome development. Rodent models have proven very good for studying the role of the maternal microbiome in fetal programming. However, some inherent limitations in these animal models make it challenging to study perinatal microbial colonization from a biomedical standpoint. In this review, we discuss the potential use of bovine animals as a biomedical model to study the maternal microbiome, in utero microbial colonization of the fetal gut, and their impact on offspring development and DOHaD. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Over the past decade, there has been a growing awareness of the vital role of the microbiome in the function of the immune system. Recently, several studies have demonstrated a relationship between the composition of the microbiome and the vaccine-specific immune response. As a result of these findings, the administration of probiotics has been proposed as a means of boosting vaccine-specific immunity. Early results have so far been highly inconsistent, with little evidence of sustained benefit. To date, a precise determination of the aspects of the microbiome that impact immunity is still lacking, and the mechanisms of action are also unknown. Further investigations into these questions are necessary to effectively manipulate the microbiome for the purpose of boosting immunity and enhancing vaccine-specific responses in infants. In this review, we summarize recent studies aimed at altering the neonatal gut microbiome to enhance vaccine responses and highlight gaps in knowledge and understanding. We also discuss research strategies aimed at filling these gaps and developing potential therapeutic interventions.

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 human microbiome plays a number of critical roles in host physiology. Evidence from longitudinal cohort studies and animal models strongly supports the theory that maldevelopment of the microbiome in early life can programme later-life disease. The early-life microbiome develops in a clear stepwise manner over the first 3 years of life. During this highly dynamic time, insults such as antibiotic use and formula feeding can adversely affect the composition and temporal development of the microbiome. Such experiences predispose infants for the development of chronic health conditions later in life. This review highlights key factors that disrupt the early-life microbiome and highlights major non-communicable diseases which are underpinned by early-life dysbiosis. [ABSTRACT FROM AUTHOR]

The microbial communities residing within the gastrointestinal and reproductive tracts are vital to cattle health; not only for their involvement in nutrient metabolism, but also for their ability to influence infectious and metabolic diseases as well as reproductive efficiency. Therefore, harnessing the ruminal and vagino-uterine microbiomes for improved cattle health and productivity have recently become an active area of research in an era where microbiome manipulation holds as much potential as genetic selection and management refinement for enhancing herd productivity. New developments highlight that the maternal gut and reproductive microbiome extend their impact to offspring development and health. These developments include the demonstrations of maternal gut microbiota involvement in developmental programming in murine models, and increased evidence supporting the existence of in utero microbial colonization and the role of maternal nutrition on fetal programming in cattle. Our recent work has focused on understanding the role of the maternal microbiota and feto-maternal microbial crosstalk in fetal programming and offspring microbiome development. Our lab has investigated the impacts of maternal dietary restriction, supplementation of one carbon metabolites or vitamins and minerals during gestation on maternal ruminal and vaginal microbiota; as well as pre- and postnatal microbial colonization in offspring calves. Our results indicate that maternal dietary alterations during pregnancy may influence ruminal and vaginal microbiota of dams, which may subsequently impact early life microbial colonization in calves being gestated. Our findings call for further research in the area of maternal gut and reproductive microbiome alterations and their impacts on fetal programming and offspring development in ruminants. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Interest Dr. Buck is a member of the Scientific Advisory Board of Juno, LTD.; a startup biotech firm focused on using the vaginal microbiome to address issues of women’s gynecologic and reproductive health. The remaining authors declare no competing interests.

Complications of pregnancy are associated with adverse outcomes for mother and baby in the short and long term. The gut microbiome has been identified as a key factor for maintaining health outside of pregnancy and could contribute to pregnancy complications. In addition, the vaginal and the recently revealed placental microbiome are altered in pregnancy and may play a role in pregnancy complications. Probiotic supplementation could help to regulate the unbalanced microflora composition observed in obesity and diabetes. Here, the impact of probiotic supplementation during pregnancy and infancy is reviewed. There are indications for a protective role in preeclampsia, gestational diabetes mellitus, vaginal infections, maternal and infant weight gain and allergic diseases. Large, well-designed randomised controlled clinical trials along with metagenomic analysis are needed to establish the role of probiotics in adverse pregnancy and infancy outcomes. [ABSTRACT FROM AUTHOR]

• Acute maternal fluoxetine treatment during pregnancy alters the fetal brain transcriptome. • Depletion of the microbiota modifies fetal brain responses to maternal fluoxetine treatment. • Opcml expression is regulated by maternal fluoxetine treatment and the maternal microbiota. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment by women experiencing depression during pregnancy. However, the effects of maternal SSRI use on early offspring development remain poorly understood. Recent studies suggest that SSRIs can modify the gut microbiota and interact directly with particular gut bacteria, raising the question of whether the gut microbiome impacts host responses to SSRIs. In this study, we investigate effects of prenatal SSRI exposure on fetal neurodevelopment and further evaluate potential modulatory influences of the maternal gut microbiome. We demonstrate that maternal treatment with the SSRI fluoxetine induces widespread alterations in the fetal brain transcriptome during midgestation, including increases in the expression of genes relevant to synaptic organization and neuronal signaling and decreases in the expression of genes related to DNA replication and mitosis. Notably, maternal fluoxetine treatment from E7.5 to E14.5 has no overt effects on the composition of the maternal gut microbiota. However, maternal pretreatment with antibiotics to deplete the gut microbiome substantially modifies transcriptional responses of the fetal brain to maternal fluoxetine treatment. In particular, maternal fluoxetine treatment elevates localized expression of the opioid binding protein/cell adhesion molecule like gene Opcml in the fetal thalamus and lateral ganglionic eminence, which is prevented by maternal antibiotic treatment. Together, these findings reveal that maternal fluoxetine treatment alters gene expression in the fetal brain through pathways that are impacted, at least in part, by the presence of the maternal gut microbiota. [ABSTRACT FROM AUTHOR]