Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort.

BACKGROUND: The gut microbiome is central to human health, but the potential impact of ozone (O3) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 exposure and the variations of the human gut microbiome during the first two years of life. DESIGN: A cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16 S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 exposure and gut microbiome features. RESULTS: Prenatal O3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 exposure explained 13.1 % of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 exposure was negatively associated with variations of Streptococcus (p-value = 0.001, q-value = 0.005), Enterococcus (p-value = 0.001, q-value = 0.005), Escherichia-Shigella (p-value = 0.010, q-value = 0.025), and Bifidobacterium (p-value = 0.003, q-value = 0.010). CONCLUSIONS: This study is the first to examine the effects of prenatal O3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.

Short-term exposures to PM2.5, PM2.5 chemical components, and antenatal depression: Exploring the mediating roles of gut microbiota and fecal short-chain fatty acids.

BACKGROUND: PM2.5 and its chemical components increase health risks and are associated with depression and gut microbiota. However, there is still limited evidence on whether gut microbiota and short-chain fatty acids (SCFAs) mediate the association between PM2.5, PM2.5 chemical components, and antenatal depression. The purpose of this study was to investigate the mediating role of maternal gut microbiota in correlations between short-term exposure to PM2.5, short-term exposure to PM2.5 chemical components, and antenatal depression. METHODS: Demographic information and stool samples were collected from 75 pregnant women in their third trimester. Their exposure to PM2.5 and PM2.5 chemical components was measured. Participants were divided into the non-antenatal depression group or the antenatal depression group according to the cut-off of 10 points on the Edinburgh Postnatal Depression Scale (EPDS). The gut microbiota were analyzed using the 16 S rRNA-V3/V4 gene sequence, and the concentration of PM2.5 and its chemical components was calculated using the Tracking Air Pollution in China (TAP) database. Gas chromatography-mass spectrometry was used to analyze SCFAs in stool samples. In order to assess the mediating effects of gut microbiota and SCFAs, mediation models were utilized. RESULTS: There were significant differences between gut microbial composition and SCFAs concentrations between the non-antenatal depression group and the antenatal depression group. PM2.5 and its chemical components were positively associated with EPDS scores and negatively associated with genera Enterococcus and Enterobacter. Genera Candidatus_Soleaferrea (ß = -7.21, 95%CI -11.00 to -3.43, q = 0.01) and Enterococcus (ß = -2.37, 95%CI -3.87 to -0.87, q = 0.02) were negatively associated with EPDS scores, indicating their potential protective effects against antenatal depression. There was no significant association between SCFAs and EPDS scores. The mediating role of Enterococcus between different lagged periods of PM2.5, PM2.5 chemical component exposure, and antenatal depression was revealed. For instance, Enterococcus explained 29.23% (95%CI 2.16-87.13%, p = 0.04) of associations between PM2.5 exposure level at the day of sampling (lag 0) and EPDS scores. CONCLUSION: Our study highlights that Enterococcus may mediate the associations between PM2.5, PM2.5 chemical components, and antenatal depression. The mediating mechanism through which the gut microbiota influences PM2.5-induced depression in pregnant women still needs to be further studied.

Postnatal nighttime light exposure and infant temperament at age 12 months: mediating role of genus Akkermansia.

The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.

Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?

BACKGROUND: Ambient air pollutant exposure can change the composition of gut microbiota at 6-months of age, but there is no epidemiological evidence on the impacts of exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during pregnancy on gut microbiota in mothers and neonates. We aimed to determine if gestational PM1 exposure is associated with the gut microbiota of mothers and neonates. METHODS: Leveraging a mother-infant cohort from the central region of China, we estimated the exposure concentrations of PM1 during pregnancy based on residential address records. The gut microbiota of mothers and neonates was analyzed using 16 S rRNA V3-V4 gene sequences. Functional pathway analyses of 16 S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The impact of PM1 exposure on α-diversity, composition, and function of gut microbiota in mothers and neonates was evaluated using multiple linear regression, controlling for nitrogen dioxide (NO2) and ozone (O3). Permutation multivariate analysis of variance (PERMANOVA) was used to analyze the interpretation degree of PM1 on the sample differences at the OTU level using the Bray-Curtis distance algorithm. RESULTS: Gestational PM1 exposure was positively associated with the α-diversity of gut microbiota in neonates and explained 14.8% (adj. P = 0.026) of the differences in community composition among neonatal samples. In contrast, gestational PM1 exposure had no impact on the α- and ß-diversity of gut microbiota in mothers. Gestational PM1 exposure was positively associated with phylum Actinobacteria of gut microbiota in mothers, and genera Clostridium_sensu_stricto_1, Streptococcus, Faecalibacterium of gut microbiota in neonates. At Kyoto Encyclopedia of Genes and Genomes pathway level 3, the functional analysis results showed that gestational PM1 exposure significantly down-regulated Nitrogen metabolism in mothers, as well as Two-component system and Pyruvate metabolism in neonates. While Purine metabolism, Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, and Ribosome in neonates were significantly up-regulated. CONCLUSIONS: Our study provides the first evidence that exposure to PM1 has a significant impact on the gut microbiota of mothers and neonates, especially on the diversity, composition, and function of neonatal meconium microbiota, which may have important significance for maternal health management in the future.

Interleukin-2 mediated associations between gut microbiota and acute myeloid leukemia: A population-based mediation Mendelian randomization study.

The relationship between the gut microbiota and acute myeloid leukemia (AML) has been established, but the exact role of interleukin (IL) in mediating this relationship has remained unclear. This study aimed to utilize whether interleukins mediate the relationships between gut microbiota and AML, thereby identifying potential novel targets for future AML treatment. Mendelian randomization (MR) is a method for finding the causality of exposure and outcome. Final instrumental variables were selected based on MR assumptions, and used to judge validity of the results. Our study identified risk and protective factors for AML, and interleukin-related gut microbiota. Finally, mediation MR analyses resulted in Interleukin-2 (IL-2) mediated associations between Clostridiaceae 1, Clostridium sensu stricto 1 and AML, with IL-2 respectively explaining 13.96 % and 12.11 % of the total effect of the aforementioned gut microbiota on AML. Our results successfully identified causal effects between specific gut microbiota, AML, and interleukins, while also elucidating the mediating role of IL-2 in these associations using MR analysis. These findings provide valuable insights into potential therapeutic targets for AML treatment.

Combined impact of Hepatitis B virus and gestational diabetes mellitus on ultrasound-measured fetal growth and adverse perinatal outcomes: A seven-year retrospective study.

AIMS: To investigate the impact of pregnancy with combined hepatitis B virus (HBV) infection and Gestational diabetes mellitus (GDM) on fetal growth and adverse perinatal outcomes. METHODS: All the pregnant women with HBV infection and/or GDM who delivered at Women's Hospital, Zhejiang University between January 2015, and September 2022 were included. A total of 1633 pregnant women were recruited in the final analysis, including 409 women with HBV infection and GDM, 396 with HBV infection only, 430 with GDM only, and 398 without HBV infection and GDM. Linear and logistic regression models were used to study the impact of pregnancy with combined HBV infection and GDM on fetal growth and adverse perinatal outcomes. RESULTS: Pregnancy with combined HBV infection and GDM was associated with increased Z-scores on primary fetal ultrasound parameters and significantly increased the risk of fetal femur length overgrowth (OR: 2.88, 95 % CI: 1.13 âˆ¼ 7.35), placental abruption (OR: 3.64, 95 % CI: 1.18 âˆ¼ 11.22), and macrosomia (OR: 4.19, 95 % CI: 1.66 âˆ¼ 10.56) compared to pregnancy without HBV infection and GDM. CONCLUSIONS: Both maternal HBV infection and GDM are independently associated with adverse perinatal outcomes. Their combination further increases the risk of adverse perinatal outcomes.

Time-varying ambient air pollution exposure is associated with gut microbiome variation in the first 2 years of life.

The infant gut microbiome matures greatly in the first year of life. Ambient air pollution (AAP) exposure is associated with the infant gut microbiome. However, whether time-varying AAP influences infant gut microbiome variation is rarely investigated. This study aimed to investigate the effects of PM2.5, PM10, and O3 on infant gut microbiome variation longitudinally. Demographic information, stool samples, and AAP exposure concentrations were collected at 6, 12, 24 months from infants. Gut microbiome was processed and analyzed using 16S rRNA V3-V4 gene regions. AAP exposure concentrations were calculated using the China High Air Pollutants (CHAP) database. Multiple pollutant models were used to assess the mixed effects of PM2.5, PM10, and O3 on infant gut microbiome variation. Infants' gut microbiomes at 6, 12, 24 months old had significant differences in alpha diversity, beta diversity, and community composition. PM2.5 and O3 respectively explained 6.3% and 5.3% of the differences in community composition for 24-month-old infants. Single pollutant exposure and multiple pollutant exposure in different periods were both associated with alpha diversity indices and specific gut microbial phyla and genera. AAP was more associated with infant gut microbial alpha diversity indices, phyla variations, and genera variations at 12-24 months than 6-12 months. Multiple pollutant exposure in 0-2 lag months showed negative correlations with 12-24 months variation in Escherichia-Shigella (ß = -0.854, 95%CI: 1.398 to -0.310) and Enterococcus (ß = -0.979, 95%CI: 1.429 to -0.530). This study highlighted that time-varying PM2.5, PM10, and O3 synergistically influenced the variation of alpha diversity and abundance of gut microbial taxa in infants. Further research is needed to explore the effects and mechanisms of other environmental exposures on infant gut microbiome variation.

Inflammatory cytokines and prenatal depression: Is there a mediating role of maternal gut microbiota?

OBJECTIVE: The mechanism of levels of inflammatory cytokines that affects brain function and mood through gut microbiota has not been fully elucidated. This study aimed to investigate the potential mediating role of gut microbiota between maternal inflammatory cytokines levels and prenatal depression. DESIGN: There were 29 women in the prenatal depression group and 27 women in the control group enrolled in this study. The Edinburgh Postnatal Depression Scale (EPDS) score of 10 was considered the cut-off value for prenatal depression. We collected demographic information, stool and blood samples. The gut microbiota was profiled using V3-V4 gene sequence of 16S rRNA, and the concentration of inflammatory cytokines were analyzed. The mediation model was analyzed by using the model 4 in the process procedure for SPSS. RESULTS: There were significance differences in the concentration of interleukin-1beta (IL-1ß)(Z = -2.383, P = 0.017) and IL-17A (Z = -2.439, P = 0.015) between the prenatal depression group and control group. There was no significant difference in α- diversity and ß-diversity between the two groups. Intestinibacter (OR: 0.012; 95% CI, 0.001-0.195) and Escherichia_Shigella (OR: 0.103; 95% CI, 0.014-0.763) were protective factors for prenatal depression, while Tyzzerella (OR: 17.941; 95% CI, 1.764-182.445) and Unclassified_f_Ruminococcaceae (OR: 22.607; 95% CI, 1.242-411.389) were risk factors. And Intestinibacter play a mediation effect between IL-17A and prenatal depression. CONCLUSION: Maternal gut microbiota is a significant mediator of the relationship between inflammatory cytokines and prenatal depression. Further research is still needed in exploring the mediating mechanisms of gut microbiota between inflammatory cytokines and depression.

Cumulative and lagged effects of varying-sized particulate matter exposure associates with toddlers' gut microbiota.

Particulate matter (PM) is an important component of air pollutants and is associated with various health risks. However, the impact of PM on toddlers' gut microbiota is rarely investigated. This study aimed to assess the cumulative and lagged effects of varying-sized PMs on toddlers' gut microbiota. We collected demographic information, stool samples, and exposure to PM from 36 toddlers aged 2-3 years. The toddlers were divided into warm season group and cooler season group according to the collection time of stool samples. The gut microbiota was processed and analyzed using 16S rRNA V3-V4 gene regions. The concentration of PM was calculated using China High Air Pollutants (CHAP) database. To assess the mixed effects of varying-sized PM, multiple-PM models were utilized. There were significant differences between the community composition, α- and ß-diversity between two groups. In multiple-PM models, there was a significant effect of weight quantile sum (PM1, PM2.5, and PM10) on α-diversity indices. In weight quantile sum models, after adjusting for a priori confounders, we found a negative effect of weight quantile sum on Enterococcus (ß = -0.134, 95% CI -0.263 to -0.006), positive effects of weight quantile sum on unclassified_f__Ruminococcaceae (ß = 0.247, 95% CI 0.102 to 0.393), Ruminococcus_1 (ß = 0.444, 95% CI 0.238 to 0.650), unclassified_f__Lachnospiraceae (ß = 0.278, 95% CI 0.099 to 0.458), and Family_XIII_AD_3011_group (ß = 0.254, 95% CI 0.086 to 0.422) in WSG and CSG. In lagged weight quantile sum models, the correlation between lag time PM levels and the gut microbiota showed seasonal trends, and weights of PM changed with lag periods. This is the first study to highlight that cumulative and lagged effects of PMs synergistically affect the diversities (α- and ß-diversity) and abundance of the gut microbiota in toddlers. Further research is needed to explore the mediating mechanism of varying-sized PMs exposure on the gut microbiota in toddlers.