Opioid-induced dysbiosis of maternal gut microbiota during gestation alters offspring gut microbiota and pain sensitivity.

There has been a rapid increase in neonates born with a history of prenatal opioid exposure. How prenatal opioid exposure affects pain sensitivity in offspring is of interest, as this may perpetuate the opioid epidemic. While few studies have reported hypersensitivity to thermal pain, potential mechanisms have not been described. This study posits that alterations in the gut microbiome may underly hypersensitivity to pain in prenatally methadone-exposed 3-week-old male offspring, which were generated using a mouse model of prenatal methadone exposure. Fecal samples collected from dams and their offspring were subjected to 16s rRNA sequencing. Thermal and mechanical pain were assessed using the tail flick and Von Frey assays. Transcriptomic changes in whole brain samples of opioid or saline-exposed offspring were investigated using RNA-sequencing, and midbrain sections from these animals were subjected to qPCR profiling of genes related to neuropathic and inflammatory pain pathways. Prenatal methadone exposure increased sensitivity to thermal and mechanical pain and elevated serum levels of IL-17a. Taxonomical analysis revealed that prenatal methadone exposure resulted in significant alterations in fecal gut microbiota composition, including depletion of Lactobacillus, Bifidobacterium, and Lachnospiracea sp and increased relative abundance of Akkermansia, Clostridium sensu stricto 1, and Lachnoclostridium. Supplementation of the probiotic VSL#3 in dams rescued hypersensitivity to thermal and mechanical pain in prenatally methadone-exposed offspring. Similarly, cross-fostering prenatally methadone-exposed offspring to control dams also attenuated hypersensitivity to thermal pain in opioid-exposed offspring. Modulation of the maternal and neonatal gut microbiome with probiotics resulted in transcriptional changes in genes related to neuropathic and immune-related signaling in whole brain and midbrain samples of prenatally methadone-exposed offspring. Together, our work provides compelling evidence of the gut-brain-axis in mediating pain sensitivity in prenatally opioid-exposed offspring.

The long-term gut bacterial signature of a wild primate is associated with a timing effect of pre- and postnatal maternal glucocorticoid levels.

BACKGROUND: During development, elevated levels of maternal glucocorticoids (GCs) can have detrimental effects on offspring morphology, cognition, and behavior as well as physiology and metabolism. Depending on the timing of exposure, such effects may vary in strength or even reverse in direction, may alleviate with age, or may concern more stable and long-term programming of phenotypic traits. Maternal effects on gut bacterial diversity, composition, and function, and the persistence of such effects into adulthood of long-lived model species in the natural habitats remain underexplored. RESULTS: In a cross-sectional sample of infant, juvenile, and adult Assamese macaques, the timing of exposure to elevated maternal GCs during ontogeny was associated with the gut bacterial community of the offspring. Specifically, naturally varying maternal GC levels during early but not late gestation or lactation were associated with reduced bacterial richness. The overall effect of maternal GCs during early gestation on the gut bacterial composition and function exacerbated with offspring age and was 10 times stronger than the effect associated with exposure during late prenatal or postnatal periods. Instead, variation in maternal GCs during the late prenatal or postnatal period had less pronounced or less stable statistical effects and therefore a weaker effect on the entire bacterial community composition, particularly in adult individuals. Finally, higher early prenatal GCs were associated with an increase in the relative abundance of several potential pro-inflammatory bacteria and a decrease in the abundance of Bifidobacterium and other anti-inflammatory taxa, an effect that exacerbated with age. CONCLUSIONS: In primates, the gut microbiota can be shaped by developmental effects with strong timing effects on plasticity and potentially detrimental consequences for adult health. Together with results on other macaque species, this study suggests potential detrimental developmental effects similar to rapid inflammaging, suggesting that prenatal exposure to high maternal GC concentrations is a common cause underlying both phenomena. Our findings await confirmation by metagenomic functional and causal analyses and by longitudinal studies of long-lived, ecologically flexible primates in their natural habitat, including developmental effects that originate before birth. Video Abstract.

Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy.

BACKGROUND: Hyperglycaemia in pregnancy (HIP) is a common metabolic disorder that not only poses risks to maternal health but also associates with an increased risk of diabetes among offspring. Vertical transmission of microbiota may influence the offspring microbiome and subsequent glucose metabolism. However, the mechanism by which maternal gut microbiota may influence glucose metabolism of the offspring remains unclear and whether intervening microbiota vertical transmission could be used as a strategy to prevent diabetes in the offspring of mothers with HIP has not been investigated. So we blocked vertical transmission to investigate its effect on glucose metabolism in the offspring. RESULTS: We established a murine HIP model with a high-fat diet (HFD) and investigated the importance of vertical transmission of gut microbiota on the glucose metabolism of offspring via birth and nursing by blocking these events through caesarean section (C-section) and cross-fostering. After weaning, all offspring were fed a normal diet. Based on multi-omics analysis, biochemical and transcriptional assays, we found that the glucometabolic deficits in the mothers were subsequently 'transmitted' to the offspring. Meanwhile, the partial change in mothers' gut microbial community induced by HIP could be transmitted to offspring, supported by the closed clustering of the microbial structure and composition between the offspring and their mothers. Further study showed that the microbiota vertical transmission was blocked by C-section and cross-fostering, which resulted in improved insulin sensitivity and islet function of the offspring of the mothers with HIP. These effects were correlated with changes in the relative abundances of specific bacteria and their metabolites, such as increased relative abundances of Bifidobacterium and short-chain fatty acids. In particular, gut microbial communities of offspring were closely related to those of their foster mothers but not their biological mothers, and the effect of cross-fostering on the offspring's gut microbiota was more profound than that of C-section. CONCLUSION: Our study demonstrates that the gut microbiota transmitted via birth and nursing are important contributors to the glucose metabolism phenotype in offspring. Video Abstract.

Maternal vaccination against group B Streptococcus glyceraldehyde-3-phosphate dehydrogenase leads to gut dysbiosis in the offspring.

Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1ß, IL-17A, RegIIIγ and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C+ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.

Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells.

Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.

The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model.

Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.

Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome-like phenotypes in prenatally androgenized female mice.

It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the ß-diversity differed from control at 8 weeks. However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice. Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life.

Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study.

Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc's classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1-V2) from vaginal samples were sequenced and analyzed. Using a random forest algorithm, the bacterial species associated with CAM were identified, and a predictive CAM (PCAM) scoring method was developed. The α diversity was significantly higher in the CAM than in the non-CAM group (P < 0.001). The area under the curve was 0.849 (95% confidence interval 0.765-0.934) using the PCAM score. Among patients at < 35 weeks of gestation, the PCAM group (n = 22) had a significantly shorter extended gestational period than the non-PCAM group (n = 25; P = 0.022). Multivariate analysis revealed a significant difference in the frequency of developmental disorders in 3-year-old infants (PCAM, 28%, non-PCAM, 4%; P = 0.022). Analyzing vaginal microbiota can evaluate the risk of IAI. Future studies should establish appropriate interventions for IAI high-risk patients to improve perinatal prognosis.

Exposure to antibiotics during pregnancy alters offspring outcomes.

INTRODUCTION: The composition of microorganisms is closely related to human health. Antibiotic use during pregnancy may have adverse effects on the neonatal gut microbiome and subsequently affect infant health development, leading to childhood atopy and allergic diseases, intestinal, metabolic and brain disorders, and infection. AREAS COVERED: This review includes the effect of maternal antibiotic use during pregnancy on potential diseases in animals and human offspring. EXPERT OPINION: Exposure to antibiotics during pregnancy alters offspring outcomes. Alterations in the microbiome may potentially lower the risk of a range of problems and may also be a novel therapeutic target in children later in life.

Prenatal stress-induced disruptions in microbial and host tryptophan metabolism and transport.

The aromatic amino acid tryptophan (Trp) is a precursor for multiple metabolites that can steer proper immune and neurodevelopment as well as social behavior in later life. Dysregulation in the Trp metabolic pathways and abundance of Trp or its derivatives, including indoles, kynurenine (Kyn), and particularly serotonin, has been associated with behavioral deficits and neuropsychiatric disorders including autism spectrum disorders (ASD) and schizophrenia. Previously, we have shown that prenatal stress (PNS) alters placental Trp and serotonin, and reduces Trp-metabolizing members of the maternal colonic microbiota. Given that PNS also results in alterations in offspring neurodevelopment, behavior and immune function, we hypothesized that PNS affects Trp metabolism and transport in both the maternal and fetal compartments, and that these alterations continue into adolescence. We surmised that this is due to reductions in Trp-metabolizing microbes that would otherwise reduce the Trp pool under normal metabolic conditions. To test this, pregnant mice were exposed to a restraint stressor and gene expression of enzymes involved in Trp and serotonin metabolism were measured. Specifically, tryptophan 2,3-dioxygenase, aryl hydrocarbon receptor, and solute carrier proteins, were altered due to PNS both prenatally and postnatally. Additionally, Parasutterella and Bifidobacterium, which metabolize Trp in the gut, were reduced in both the dam and the offspring. Together, the reductions of Trp-associated microbes and concomitant dysregulation in Trp metabolic machinery in dam and offspring suggest that PNS-induced Trp metabolic dysfunction may mediate aberrant fetal neurodevelopment.

Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane.

Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.

Effects of S24-7 on the weight of progeny rats after exposure to ceftriaxone sodium during pregnancy.

Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old. To determine the role of the gut microbiota and its metabolites in the growth of offspring, we collected feces for sequencing and further established that the experimental group has a different composition ratio of dominant bacteria at 6 week old, among which S24-7 correlated negatively with body weight and the metabolites that correlated with body weight-related unique flora were L-Valine, L-Leucine, Glutaric acid, N-Acetyl-L-glutamate, and 5-Methylcytosine. To further explore how they affect the growth of offspring, we submitted these data to Kyoto Encyclopedia of Genes and Genomes website for relevant pathway analysis. The results showed that compared with the control, the following metabolic pathways changed significantly: Valine, leucine, and isoleucine biosynthesis; Protein digestion and absorption; and Mineral absorption. Therefore, we believe that our findings support the conclusion that ceftriaxone sodium exposure in pregnancy has a long-lasting adverse effect on the growth of offspring because of an imbalance of gut microbiota, especially S24-7, via different metabolic pathways.

Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams.

The risk of recurrence of estrogen receptor-positive breast cancer remains constant, even 20 years after diagnosis. Recurrence may be more likely in patients pre-programmed for it already in the womb, such as in the daughters born to obese mothers. Maternal obesity persistently alters offspring's gut microbiota and impairs tumor immune responses. To investigate if the gut dysbiosis is linked to increased risk of mammary cancer recurrence in the offspring of obese rat dams, we fed adult offspring genistein which is known to have beneficial effects on the gut bacteria. However, the effects of genistein on breast cancer remain controversial. We found that genistein intake after tamoxifen response prevented the increased risk of local recurrence in the offspring of obese dams but had no effect on the control offspring. A significant increase in the abundance of inflammatory Prevotellaceae and Enterobacteriaceae, and a reduction in short-chain fatty acid producing Clostridiaceae was observed in the offspring of obese dams. Genistein supplementation reversed these changes as well as reversed increased gut metabolite N-acetylvaline levels which are linked to increased all-cause mortality. Genistein supplementation also reduced genotoxic tyramine levels, increased metabolites improving pro-resolving phase of inflammation, and reversed the elevated tumor mRNA expression of multiple immunosuppressive genes in the offspring of obese dams. If translatable to breast cancer patients, attempts to prevent breast cancer recurrences might need to focus on dietary modifications which beneficially modify the gut microbiota.

Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy.

Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.

Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index.

Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition and function during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. We studied 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). BMI was higher among ASB-exposed infants. Infant stool (16S rRNA gene sequencing) and urine (untargeted metabolomics) were acquired in early (3-4 months) and late (12 months) infancy. We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature (Cluster 1) to mature (Cluster 4) and two deviated from this trajectory (Clusters 2 and 3). Maternal ASB consumption did not differ between clusters, but was associated with community-level shifts in infant gut bacterial taxonomy structure and depletion of several Bacteroides sp. in Cluster 2. In the complete dataset, urine succinate and spermidine levels at 3 months were higher in ASB-exposed infants, and urine succinate was positively associated with BMI at one-year-old. Overall, gestational exposure to ASB was associated with gut microbiota structure in infants from Cluster 2, and gut microbiota structure was associated with infant BMI. Gestational exposure to ASB was positively associated with infant urine succinate and spermidine. Succinate was found to mediate 29% of the effect of ASB exposure on BMI at one-year-old, revealing a potential role of this metabolite in increased infant weight linked to gestational ASB consumption. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal relationships between maternal ASB consumption (a modifiable exposure), gut microbiota and metabolites, infant metabolism, and body composition.

Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus, Flavonifractor, Erysipelotrichaceae, and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function (Phascolarctobacterium). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease.

Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites.

Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.

Imbalance of gut microbiota and fecal metabolites in offspring female mice induced by nitenpyram exposure during pregnancy.

Ubiquitous exposure to the neonicotinoid insecticide nitenpyram has raised concerns about its potential toxicity. In this study, we explored its health effects on the female offspring of mice that had been exposed during pregnancy. We found that exposure of pregnant mice to nitenpyram resulted in decreased levels of serum triglycerides, total cholesterol, and glucose in female offspring, and additional research uncovered gut microbiota disturbances, accompanied by abnormal fecal metabolic profiles. Based on Pearson correlation analysis, we found that decreased abundance of Lactobacillus may play the most critical role, and changes in gut bacterial purine metabolism, BCAAs metabolism, and the TCA cycle are all closely related to the abundance of Lactobacillus. In summary, these results help explain the observed serum biochemical abnormalities and provide new insights into the intergenerational toxicity of nitenpyram.