Maternal Microbiome Research Articles

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.

Oral microbiome and preterm birth.

The etiology of preterm birth (PTB) is heterogeneous and not yet well known. Maternal periodontal disease has been investigated for decades and is a known risk factor for adverse pregnancy outcomes. However, no particular bacterial species or higher taxonomic order has been found as causative of PTB, leading to studies of the whole oral microbiome. In order to determine if and how the composition of the oral microbiome is associated with PTB, we performed a large case-control study including women with term (TB) and PTB. We compared oral microbiomes in PTB to TB, to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained oral swab samples from 152 Caucasian pregnant women who were classified as either PTB (≤36 6/7 weeks, n = 61) or TB (≥38 0/7 weeks, n = 91) in exclusion of any other major medical or obstetric conditions. The oral microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform. The dominant microorganisms at the phylum level in all pregnant women regardless of birth week outcomes as belonging to Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria. The phyla Firmicutes and Bacteroidetes were relatively more abundant in women with a PTB than in women with a TB, while Proteobacteria was less prevalent in women with a PTB. At the genus level, Veillonella, Prevotella, and Capnocytophaga were enriched in the PTB, and while many of the members of these genera could not be resolved to the species level, Veillonella massillensis was shown to be increased in the PTB group. We identified the genera Veillonella, Prevotella, and Capnocytophaga in the maternal oral microbiome as being associated with PTB independently of clinically apparent infection, uterine anomalies, and other pregnancy complications, including placenta previa, and placental abruption. The clarification of the role of those taxa in the etiology of PTB merits further research.

Similarities in rotavirus vaccine viral shedding and immune responses in pairs of twins.

Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models. A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose (P=0.049) and RV IgG titers during the entire observation period (P=0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response. The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis.

P27-021-23 Fetal Cognitive Neurodevelopment by the Maternal Gut Microbiome Remodeling by β-Glucan Supplementation in Mice

P27-021-23 Fetal Cognitive Neurodevelopment by the Maternal Gut Microbiome Remodeling by β-Glucan Supplementation in Mice

Maternal microbis: How kinship composes reproductive relations for a human‐bovine maternal microbiome

AbstractReading across a burgeoning scientific literature that conflates microbial dynamics between mother:child bodies with normative mothering practices, we offer a model of maternal microbis that troubles the distinctions between productive and reproductive relations. We ground this argument in a systematic analysis of the content and circulation of descriptive maternal microbiome research between 2007 and 2021 along with the proliferation of lay narratives about the maternal microbiome inspired by such research. Following this research across the species line between human and bovine bodies, we trace the gendered effects of using humans as model animals and tie current microbiome hype to a much longer history of entangling reproductive and productive labors. More than a microbial retread of a familiar story within a history of distributing reproductive labor to other bodies, our focus on the maternal microbis as a gendered model of microbial relations enables us to ask specific questions about the effects of centering microbes into models of reproductive bodies (both Homo and Bos), leading us to consider how expectations of gendered care and gendered bodies make certain paradigms possible and foreclose others.

Birth Mode Does Not Determine the Presence of Shared Bacterial Strains between the Maternal Vaginal Microbiome and the Infant Stool Microbiome.

Dysbiosis of the neonatal gut microbiome during early life has been suggested as the missing link that may explain higher rates of certain diseases in caesarean section-delivered infants. Many studies report delivery mode-related dysbiosis in infants due to a lack of maternal vaginal microbiome exposure, prompting interventions to correct the neonatal gut microbiome by transferring these missing microbes after caesarean delivery. The maternal vaginal microbiome is among the first microbial exposures that many infants experience, yet little is known about the extent of direct transmission of maternal vaginal microbes. As part of the Maternal Microbiome Legacy Project, we aimed to determine if maternal vaginal bacteria are vertically transmitted to infants. We employed cpn60 microbiome profiling, culture-based screening, molecular strain typing, and whole-genome sequencing to determine whether identical maternal vaginal strains were present in infant stool microbiomes. We identified identical cpn60 sequence variants in both halves of maternal-infant dyads in 204 of 585 Canadian women and their newborn infants (38.9%). The same species of Bifidobacterium and Enterococcus were cultured from maternal and corresponding infant samples in 33 and 13 of these mother-infant dyads, respectively. Pulsed-field gel electrophoresis and whole-genome sequencing determined that near-identical strains were detected in these dyads irrespective of delivery mode, indicating an alternative source in cases of caesarean delivery. Overall, we demonstrated that vertical transmission of maternal vaginal microbiota is likely limited and that transmission from other maternal body sites, such as the gut and breast milk, may compensate for the lack of maternal vaginal microbiome exposure during caesarean delivery. IMPORTANCE The importance of the gut microbiome in human health and disease is widely recognized, and there has been a growing appreciation that alterations in gut microbiome composition during a "critical window" of development may impact health in later life. Attempts to correct gut microbiome dysbiosis related to birth mode are underpinned by the assumption that the lack of exposure to maternal vaginal microbes during caesarean delivery is responsible for dysbiosis. Here, we demonstrate that there is limited transmission of the maternal vaginal microbiome to the neonatal gut, even in cases of vaginal delivery. Furthermore, the presence of identical strains shared between mothers and infants in early life, even in cases of caesarean delivery, highlights compensatory microbial exposures and sources for the neonatal stool microbiome other than the maternal vagina.

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.

Prematurely delivering mothers show reductions of lachnospiraceae in their gut microbiomes

BackgroundPreterm birth is the leading cause of perinatal morbidity and mortality. Despite evidence shows that imbalances in the maternal microbiome associates to the risk of preterm birth, the mechanisms underlying the association between a perturbed microbiota and preterm birth remain poorly understood.MethodApplying shotgun metagenomic analysis on 80 gut microbiotas of 43 mothers, we analyzed the taxonomic composition and metabolic function in gut microbial communities between preterm and term mothers.ResultsGut microbiome of mothers delivering prematurely showed decreased alpha diversity and underwent significant reorganization, especially during pregnancy. SFCA-producing microbiomes, particularly species of Lachnospiraceae, Ruminococcaceae, and Eubacteriaceae, were significantly depleted in preterm mothers. Lachnospiraceae and its species were the main bacteria contributing to species’ differences and metabolic pathways.ConclusionGut microbiome of mothers delivering prematurely has altered and demonstrates the reduction of Lachnospiraceae.

Maternal Nutritional Status and the Microbiome across the Pregnancy and the Post-Partum Period.

Appropriate nutrition during pregnancy and the post-partum period is vital for both the mothers and their offspring. Both under- and over-nourished status may have important microbial implications on the maternal and infant gut microbiomes. Alterations in the microbiome can have implications for a person's risk of obesity and metabolic diseases. In this review, we examine alterations in the maternal gut, vaginal, placental, and milk microbiomes in the context of pre-pregnancy BMI, gestational weight gain, body composition, gestational diabetes, and maternal diet. We also investigate how the infant gut microbiome may be altered by these different parameters. Many of the microbial changes seen in under- and over-nourished states in birthing parents may result in long-term implications for the health of offspring. Differences in diet appear to be a major driver of the maternal and subsequently milk and offspring microbiomes. Further prospective longitudinal cohort studies are needed to examine nutrition and the microbiome to better understand its implications. Additionally, trials involving dietary interventions in child-bearing age adults should be explored to improve the mother and child's risks for metabolic diseases.

The Effect of Antibiotics Treatment on the Maternal Immune Response and Gut Microbiome in Pregnant and Non-Pregnant Mice

The gut microbiota are involved in adaptations of the maternal immune response to pregnancy. We therefore hypothesized that inducing gut dysbiosis during pregnancy alters the maternal immune response. Thus, pregnant mice received antibiotics from day 9 to day 16 to disturb the maternal gut microbiome. Feces were collected before, during and after antibiotic treatment, and microbiota were measured using 16S RNA sequencing. Mice were sacrificed at day 18 of pregnancy and intestinal (Peyer’s patches (PP) and mesenteric lymph nodes (MLN)) and peripheral immune responses (blood and spleen) were measured using flow cytometry. Antibiotic treatment decreased fetal and placental weight. The bacterial count and the Shannon index were significantly decreased (Friedman, followed by Dunn’s test, p < 0.05) and the bacterial genera abundance was significantly changed (Permanova, p < 0.05) following antibiotics treatment as compared with before treatment. Splenic Th1 cells and activated blood monocytes were increased, while Th2, Th17 and FoxP3/RoRgT double-positive cells in the PP and MLNs were decreased in pregnant antibiotics-treated mice as compared with untreated pregnant mice. In addition, intestinal dendritic cell subsets were affected by antibiotics. Correlation of immune cells with bacterial genera showed various correlations between immune cells in the PP, MLN and peripheral circulation (blood and spleen). We conclude the disturbed gut microbiota after antibiotics treatment disturbed the maternal immune response. This disturbed maternal immune response may affect fetal and placental weight.

Maternal diet and gut microbiome composition modulate early‐life immune development

In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ‐free mice with a consortium of 14 strains, fed them a standard fiber‐rich chow or a fiber‐free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber‐rich diet, pups of fiber‐deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin‐foraging bacterium that can also use milk oligosaccharides. The pups of fiber‐deprived dams exhibited an enrichment of colonic transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A. muciniphila from the community, but maintenance on the fiber‐rich diet, was associated with reduced proportions of RORγt‐positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development.

Evaluating Current Molecular Techniques and Evidence in Assessing Microbiome in Placenta-Related Health and Disorders in Pregnancy

The microbiome is of great interest due to its potential influence on the occurrence and treatment of some human illnesses. It may be regarded as disruptions to the delicate equilibrium that humans ordinarily maintain with their microorganisms or the microbiota in their environment. The focus of this review is on the methodologies and current understanding of the functional microbiome in pregnancy outcomes. We present how novel techniques bring new insights to the contemporary field of maternal–fetal medicine with a critical analysis. The maternal microbiome in late pregnancy has been extensively studied, although data on maternal microbial changes during the first trimester are rare. Research has demonstrated that, in healthy pregnancies, the origin of the placental microbiota is oral (gut) rather than vaginal. Implantation, placental development, and maternal adaptation to pregnancy are complex processes in which fetal and maternal cells interact. Microbiome dysbiosis or microbial metabolites are rising as potential moderators of antenatal illnesses related to the placenta, such as fetal growth restriction, preeclampsia, and others, including gestational diabetes and preterm deliveries. However, because of the presence of antimicrobial components, it is likely that the bacteria identified in placental tissue are (fragments of) bacteria that have been destroyed by the placenta’s immune cells. Using genomic techniques (metagenomics, metatranscriptomics, and metaproteomics), it may be possible to predict some properties of a microorganism’s genome and the biochemical (epigenetic DNA modification) and physical components of the placenta as its environment. Despite the results described in this review, this subject needs further research on some major and crucial aspects. The phases of an in utero translocation of the maternal gut microbiota to the fetus should be explored. With a predictive knowledge of the impacts of the disturbance on microbial communities that influence human health and the environment, genomics may hold the answer to the development of novel therapies for the health of pregnant women.

Maternal high fat diet exposure results in maternal microbiome dependent increase in inflammatory cytokines and decrease in neurons in offspring brain.

Abstract Introduction: We hypothesized that maternal high fat diet (mHFD) exposure will result in a microbiota dependent increase in inflammation and inhibition of axonal development in offspring brain. Methods: Conventional and germ-free murine dams were exposed to 60% high fat diet (HFD) or regular diet (RD) prior to mating. Offspring brains were collected at 2-weeks of life and analyzed for inflammatory (TNF-α, IL-6, IL-17A, IL1β and TGF-β) and regulatory markers of neuronal development (Nurr1) by quantitative RT-PCR. RNA seq was performed on whole brain in conventional mice. We quantified differences in regional neurons by histology (Nissl and H&E). Behavioral studies on mHFD and RD offspring are ongoing. Results: mHFD offspring had a significant increase in the inflammatory cytokines IL-17A and IL-6 when compared to controls. Nurr1 was increased 50-fold in mHFD offspring. In germ-free mHFD offspring, there was no difference. Quantification of neurons by Nissl staining demonstrated a decrease in neuron cell count in the cortex (20% decrease), and in hippocampal regions (22% in CA2 and 32% in CA3). Preliminary RNAseq analysis showed upregulation of specific genes involved in immunoregulation, neuron development and migration, and apoptosis in mHFD offspring. Conclusion: mHFD exposure resulted in increased inflammatory cytokines and reduced neurogenesis in the offspring brain. This change was ameliorated in germ free mice, demonstrating a microbiome dependent diet effect. RNAseq findings demonstrate changes in specific immunoregulatory pathways which warrant further exploration. We speculate that maternal diet interacts with the maternal microbiome to increase immune activation in the fetal brain which affects neurogenesis. Supported by grants from NIH (R01 1K12HD068369) and Children’s Medical Center Research Grant

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.

Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex.

Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function. IMPORTANCE Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. This scenario plays out in the clinic when BCW debris released during antibiotic therapy of maternal infection traffics to the fetal brain. This study identifies the direct interaction of BCW with TLR2/6 present on the primary cilium, the signaling hub on fetal neural progenitor cells (NPCs). NPCs control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. Within a window of vulnerability before the appearance of fetal immune cells, the BCW-TLR2/6 interaction results in the inhibition of ciliogenesis, derepression of Sonic Hedgehog signaling, excess proliferation of neural progenitors, and abnormal cortical architecture. In the first example of TLR signaling linked to Sonic Hedgehog, BCW/TLR2/6 appears to act during fetal brain morphogenesis to play a role in setting the total cell number in the neocortex.

Effects of prenatal antibiotic treatment on early infant health: a retrospective study in a rural health facility in Ghana.

Infant mortality remains a major developmental challenge in many low-income countries. Epidemiological evidence suggests that infant acquisition of maternal microbiome is essential for programming of immunity and metabolism. As such, irrational maternal antibiotic use may affect infant health. The aim of the study was to determine the effects of prenatal antibiotic use on early postnatal life (90 days) in a low-income community in Ghana. The study was a retrospective study of 412 mother-baby pair medical records in a low-income community in rural Ghana. During the ninety-day period, the prevalence and relative risk of neonatal sepsis, respiratory disorders, and dermatitis were significantly higher in infants treated prenatally with antibiotics compared to untreated infants. Prenatal antibiotic treatment was not significantly associated with the risk of developing neonatal jaundice and conjunctivitis. However, prenatally antibiotic exposed infants were three times likely to visit the hospital for a non-scheduled/non-review treatment within the first 90 days compared to unexposed babies. Intrapartum antibiotic treatment is associated with poor early infant health. Rationalizing antibiotic use during pregnancy may contribute to reducing infant mortality.

Composition of the maternal gastrointestinal microbiome as a predictor of neonatal birth weight.

The biological mechanism by which the maternal gastrointestinal microbiota contributes to fetal growth and neonatal birth weight is currently unknown. The purpose of this study was to explore how the composition of the maternal microbiome in varying pre-gravid body mass index (BMI) groups are associated with neonatal birth weight adjusted for gestational age. Retrospective, cross-sectional metagenomic analysis of bio-banked fecal swab biospecimens (n = 102) self-collected by participants in the late second trimester of pregnancy. Through high-dimensional regression analysis using principal components (PC) of the microbiome, we found that the best performing multivariate model explained 22.9% of the variation in neonatal weight adjusted for gestational age. Pre-gravid BMI (p = 0.05), PC3 (p = 0.03), and the interaction of the maternal microbiome with maternal blood glucose on the glucose challenge test (p = 0.01) were significant predictors of neonatal birth weight after adjusting for potential confounders including maternal antibiotic use during gestation and total gestational weight gain. Our results indicate a significant association between the maternal gastrointestinal microbiome in the late second trimester and neonatal birth weight adjusted for gestational age. Moderated by blood glucose at the time of the universal glucose screening, the gastrointestinal microbiome may have a role in the regulation of fetal growth. Maternal blood glucose in the late second trimester significantly moderates the relationship between the maternal gastrointestinal microbiome and neonatal size adjusted for gestational age. Our findings provide preliminary evidence for fetal programming of neonatal birth weight through the maternal gastrointestinal microbiome during pregnancy.

Inulin alleviates offspring asthma by altering maternal intestinal microbiome composition to increase short-chain fatty acids.

Technically, symptom of offspring asthma is also closely reliant on its maternal high-fiber diet as well as the intestinal microbiome. Fruits and vegetables are abundant in inulin, and this naturally soluble dietary fiber is endowed with a potential value on offspring asthma control through the maternal intake, but the mechanism now remains less studied. In this study, rats were given with inulin-included drinking water, whereas in normal group rats were allowed with normal water. Afterwards, we analyzed both the formations of the offspring intestinal microbiome ahead of asthma model establishment and of the maternal intestinal microbiome through high throughput sequence and the short-chain fatty acids (SCFAs) by metabolomic analysis. Subsequently, lung inflammation indexes were detected by Elisa, and the expression of short-chain fatty acid receptors (GPR41, GPR43) in the offspring of asthma models were evaluated through qPCR assay. Inulin intake resulted in altered maternal intestinal microbiome composition, with a significant increase in SCFAs-producing bacteria (mainly Bifidobacterium), attenuating the asthmatic inflammatory response in the offspring. Meanwhile, inulin intake during pregnancy modulates the composition of the intestinal microbiome of the offspring, and this alteration appears before the onset of asthma, hence, there should be further studies onto the impacts of offspring's intestinal microbiome on asthma procession.

Revealing the importance of prenatal gut microbiome in offspring neurodevelopment in humans.

It has been widely recognized that a critical time window for neurodevelopment occurs in early life and the host's gut microbiome plays an important role in neurodevelopment. Following recent demonstrations that the maternal prenatal gut microbiome influences offspring brain development in murine models, we aim to explore whether the critical time window for the association between the gut microbiome and neurodevelopment is prenatal or postnatal for human. Here we leverage a large-scale human study and compare the associations between the gut microbiota and metabolites from mothers during pregnancy and their children with the children's neurodevelopment. Specifically, using multinomial regression integrated in Songbird, we assessed the discriminating power of the maternal prenatal and child gut microbiome for children's neurodevelopment at early life as measured by the Ages & Stages Questionnaires (ASQ). We show that the maternal prenatal gut microbiome is more relevant than the children's gut microbiome to the children's neurodevelopment in the first year of life (maximum Q2=0.212 and 0.096 separately using the taxa at the class level). Moreover, we found that Fusobacteriia is more associated with high fine motor skills in ASQ in the maternal prenatal gut microbiota but become more associated with low fine motor skills in the infant gut microbiota (rank=0.084 and-0.047 separately), suggesting the roles of the same taxa with respect to neurodevelopment can be opposite at the two stages of fetal neurodevelopment. These findings shed light, especially in terms of timing, on potential therapeutic interventions to prevent neurodevelopmental disorders. This work was supported by the National Institutes of Health (grant numbers: R01AI141529, R01HD093761, RF1AG067744, UH3OD023268, U19AI095219, U01HL089856, R01HL141826,K08HL148178, K01HL146980), and the Charles A. King Trust Postdoctoral Fellowship.

Maternal antibiotic exposure increases total islet number and volume in the neonatal pancreas and reduces HbA1c and insulitis in adult female non‐obese diabetic mice

AbstractBackgroundEarly antibiotic treatment changes susceptibility to disease in rodent models for type 1 diabetes, but the impact that gestational antibiotics may have on pancreatic embryogenesis and β cell function later in life is still unknown.MethodsOur aim was to determine whether gestational antibiotics could change islet neogenesis and function in female non‐obese diabetic mouse offspring. Stereology of pancreatic islets and insulin measurements were therefore applied to 2‐week‐old pups from mothers either exposed or not to a broad‐spectrum cocktail of ampicillin (1 g/L), vancomycin (0.5 g/L) and neomycin (1 g/L) during pregnancy. The degree of insulitis, glycated haemoglobin (HbA1c), serum cytokines and endotoxin, fasting glucose and insulin, and glucose tolerance were tested in the prediabetic pups later in life. Inflammatory and glycaemic measurements were made on the breeding females, and the gut microbiota was analysed by 16S sequencing in both the mothers and pups.ResultsAntibiotics depleted the maternal microbiome and perturbed the normal gut colonisation trajectory in the pups. While Akkermansia and Rikenellaceae were later enriched in the treated pups, Bacteroides failed to colonise post‐treatment. Antibiotic treatment reduced blood glucose in the mothers, weight of the pups, and HbA1c and insulitis in the adult offspring and increased anti‐inflammatory CD4+ natural killer T cells. This was preceded by more than 50% increase in total islet number and volume, and increased insulin levels in postnatal life. No changes were observed in their homeostatic model assessment of insulin resistance (HOMA‐IR) and β cell function (HOMA‐β), serum endotoxin or cytokine levels later in life, but the glucose tolerance response was altered in the treated offspring, which suggested an improvement in β cell exhaustion that may have left the islets less vulnerable to destruction.ConclusionOur study highlights the importance of considering maternal microbiota‐modulating factors as determinants that may mitigate or aggravate diabetes via changes in islet maturation and β cell function in perinatal life.