The intestinal microbiome is essential for gastrointestinal and overall health, yet its response to air pollution in children remains underexplored. In a study involving 412 young children from the ENVIRONAGE cohort, stool samples were analysed via Illumina Miseq sequencing to assess microbiome alpha diversity (observed richness, species evenness, and Shannon diversity) and composition. Exposure to previous year particulate air pollution (black carbon, PM2.5, coarse PM, and PM10) was modeled using high-resolution spatial-temporal interpolation models. Multiple linear regression models were adjusted for a priori selected covariables and stratified by sex. Furthermore, we performed a differential relative abundance analysis at family and genus level, while accounting for the same covariables. Statistically significant effect modification by sex was apparent for several intestinal alpha diversity indices and air pollutants. In boys, we observed negative associations between particulate air pollution exposure and intestinal microbiome richness (estimates ranging from -5.55 to -9.06 per interquartile range (IQR) increase in particulate air pollution exposure) and Shannon diversity (estimates ranging from -0.058 to -0.095 per IQR increase). Differently, in girls non-significant positive associations were observed with species evenness (estimates ranging from 0.019 to 0.020 per IQR increase) and Shannon diversity (estimate 0.065 per IQR increase in black carbon). After multiple testing correction, we reported several bacterial families and genera (Streptococcaceae, Clostridiales Incertae Sedis XIII, Coriobacteriaceae, Streptococcus, and Paraprevotella) to be oppositely associated with particulate air pollution exposure in boys and girls. Our findings show a sex-dependent association between particulate air pollution exposure and intestinal microbiome composition, highlighting boys as potentially more vulnerable to diversity loss associated with childhood exposure to particulate pollution.

Skin is the exterior interface of the human body with the environment and harbors millions of microorganisms crucial for skin health. Associations between early-life green space exposure and the skin microbiome of children remain unstudied. Skin swabs were collected from 402 children (4–12 years old) enrolled in the ENVIRONAGE birth cohort. Skin alpha diversity indices and the relative abundance at family and species levels were determined using 16S rRNA gene HiFi amplicon sequencing. Total green, high-growing green, and low-growing green were estimated in several radii around their current residential and school address based on high-resolution land cover data. Multiple linear regression models between green-space indices and skin microbiome alpha diversity indices were adjusted for sex, age, frequency of soap use, maternal education, season of skin swab collection, sequencing batch, and storage duration of the skin swab. As interaction terms between green-space indices and season were borderline statistically significant, we also ran the linear regression models stratified by season. Last, we performed a differential relative abundance analysis, accounting for the covariables above. Total green and high-growing green in multiple radii (from 100 to 500 m) were positively associated with observed richness (regression coefficients ranging from 10.06 to 15.31 [P-value ranging from 0.03 to 0.12] per interquartile range increase in green). The associations were only statistically significant when skin swabs were collected in the warm season. The relative abundance of the bacterial families Xanthomonadaceae, Intrasporangiaceae, Pseudomonadaceae, and Caulobacteraceae was statistically significantly positively associated with total and high-growing green within 300 m. Our findings suggest an influential role of early-life green space exposure on skin microbiome composition. Additional research is needed to investigate whether the observed positive relationship between green space and skin bacterial richness has implications for human health.

BACKGROUND:Evidence is accumulating that elevated levels of particulate air pollution, including black carbon, have been linked to gastrointestinal disorders and a lower intestinal bacterial richness and diversity. One of the hypothesized underlying mechanisms is the absorption of air pollution-related particles from the gastrointestinal tract. METHODS:We visualized and quantified black carbon particles via white light generation under femtosecond-pulsed laser illumination in ileum and colon biopsies of five human patients. The biodistribution was assessed in three different layers (i.e., mucosa, submucosa, and muscularis propria). FINDINGS:Black carbon particles could be identified in all three tissue layers of the ileum and colon biopsies of five participants (two men and three women; mean ± standard deviation age, 76.40 ± 7.37 years), and their carbonaceous nature was confirmed via emission fingerprinting. The median (±SD) black carbon load was borderline statistically significantly higher in the ileum compared to the colon (1.21 × 105 ± 1.68 × 104 particles/mm3 versus 9.34 × 104 ± 1.33 × 104 particles/mm3; p = 0.07) and was driven by a difference in black carbon load in the submucosa layer (p = 0.01). Regarding the three tissue layers, loads were higher in the submucosa, compared with the mucosa (ileum: +76%, p < 0.0001; colon: +70%, p = 0.0001) and muscularis propria (ileum: +88%, p < 0.0001; colon: +88%, p < 0.0001). In ileum, loads were borderline higher in the mucosa versus muscularis propria (p = 0.09). INTERPRETATION:This explorative study provides real-life evidence that black carbon particles can reach the intestinal tissue and accumulate in different intestinal tissue layers. These findings support further research into how particulate air pollution directly affects gastrointestinal health. FUNDING:Thessa Van Pee holds a doctoral fellowship from the Research Foundation Flanders (FWO), grant number: 11C7421N. Tim Nawrot is a Methusalem grant holder.

BACKGROUND:The gut microbiome plays an essential role in human health. Despite the link between air pollution exposure and various diseases, its association with the gut microbiome during susceptible life periods remains scarce. OBJECTIVES:In this study, we examined the association between black carbon particles quantified in prenatal and postnatal biological matrices and bacterial richness and diversity measures, and bacterial families. METHODS:A total of 85 stool samples were collected from 4- to 6-y-old children enrolled in the ENVIRonmental influence ON early AGEing birth cohort. We performed 16S rRNA gene sequencing to calculate bacterial richness and diversity indices (Chao1 richness, Shannon diversity, and Simpson diversity) and the relative abundance of bacterial families. Black carbon particles were quantified via white light generation under femtosecond pulsed laser illumination in placental tissue and cord blood, employed as prenatal exposure biomarkers, and in urine, used as a post-natal exposure biomarker. We used robust multivariable-adjusted linear models to examine the associations between quantified black carbon loads and measures of richness (Chao1 index) and diversity (Shannon and Simpson indices), adjusting for parity, season of delivery, sequencing batch, age, sex, weight and height of the child, and maternal education. Additionally, we performed a differential relative abundance analysis of bacterial families with a correction for sampling fraction bias. Results are expressed as percentage difference for a doubling in black carbon loads with 95% confidence interval (CI). RESULTS:Two diversity indices were negatively associated with placental black carbon [Shannon: -4.38% (95% CI: -8.31%, -0.28%); Simpson: -0.90% (95% CI: -1.76%, -0.04%)], cord blood black carbon [Shannon: -3.38% (95% CI: -5.66%, -0.84%); Simpson: -0.91 (95% CI: -1.66%, -0.16%)], and urinary black carbon [Shannon: -3.39% (95% CI: -5.77%, -0.94%); Simpson: -0.89% (95% CI: -1.37%, -0.40%)]. The explained variance of black carbon on the above indices varied from 6.1% to 16.6%. No statistically significant associations were found between black carbon load and the Chao1 richness index. After multiple testing correction, placental black carbon was negatively associated with relative abundance of the bacterial families Defluviitaleaceae and Marinifilaceae, and urinary black carbon with Christensenellaceae and Coriobacteriaceae; associations with cord blood black carbon were not statistically significant after correction. CONCLUSION:Black carbon particles quantified in prenatal and postnatal biological matrices were associated with the composition and diversity of the childhood intestinal microbiome. These findings address the influential role of exposure to air pollution during pregnancy and early life in human health. https://doi.org/10.1289/EHP11257.

A healthy indigenous intestinal microbiome is essential for human health. Well-established gut microbiome determinants only explain 16% of the inter-individual variation in gut microbiome composition. Recent studies have focused on green space as a potential determinant of the intestinal microbiome. We systematically summarize all evidence concerning the association between green space and intestinal bacterial diversity, evenness, and richness indices, specific bacterial taxa, and potential underlying mechanisms. Seven epidemiological studies were included in this review. The majority of the included studies (n = 4) reported a positive association between green space and intestinal bacterial diversity, evenness, and richness, while two reported the opposite. There was little overlap between the publications regarding the association between green space and the relative abundance of specific bacterial taxa. Only a decrease in the relative abundance of Bacteroidetes, Bacteroides, and Anaerostipes and an increase in Lachnospiraceae and Ruminococcaceae were reported in multiple studies, predominantly suggesting that green space is positively associated with the intestinal microbiome composition, and subsequently with human health. Lastly, the only examined mechanism was a reduction in perceived psychosocial stress.

A healthy indigenous intestinal microbiome is indispensable for intra- and extra-intestinal human health. Since well-established factors such as diet and antibiotic use only explain 16 % of the inter-individual variation in gut microbiome composition, recent studies have focused on the association between ambient particulate air pollution and the intestinal microbiome. We systematically summarize and discuss all evidence concerning the effect of particulate air pollution on intestinal bacterial diversity indices, specific bacterial taxa, and potential underlying intestinal mechanisms. To this end, all possibly relevant publications published between February 1982 and January 2023 were screened, and eventually, 48 articles were included. The vast majority (n = 35) of these studies were animal studies. The exposure periods investigated in the human epidemiological studies (n = 12) ranged from infancy through elderly. This systematic review found that intestinal microbiome diversity indices were generally negatively associated with particulate air pollution in epidemiological studies, with an increase in taxa belonging to Bacteroidetes (two studies), Deferribacterota (one study), and Proteobacteria (four studies), a decrease in taxa belonging to Verrucomicrobiota (one study), and no consensus for taxa belonging to Actinobacteria (six studies) and Firmicutes (seven studies). There was no unequivocal effect of ambient particulate air pollution exposure on bacterial indices and taxa in animal studies. Only one study in humans examined a possible underlying mechanism; yet, the included in vitro and animal studies depicted higher gut damage, inflammation, oxidative stress, and permeability in exposed versus unexposed animals. Overall, the population-based studies showed a dose-related continuum of short- and long-term ambient particulate air pollution exposure on lower gut diversity and shifts in taxa over the entire life course.

Childhood cognitive development depends on neuroimmune interactions. Immunomodulation by early-life microbial exposure may influence neuropsychological function. In this study, we investigate the association between residential indoor microbiota and cognition and behavior among preschoolers. Indoor-settled dust bacterial and fungal characteristics were assessed using 16S and ITS amplicon sequencing (microbial diversity) and qPCR measurements (microbial loads). Child behavior was assessed using four scales: peer relationship, emotional, conduct, and hyperactivity was assessed by the Strengths and Difficulties Questionnaire (SDQ). Cognitive function was assessed using four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB) software. The first two tasks were designed to assess attention and psychomotor speed (Motor Screening (MOT) and Big/Little Circle (BLC)) and the last two to evaluate the child’s visual recognition/working memory (Spatial Span (SSP) and Delayed Matching to Sample (DMS)). Among the 172 included children (age 4–6 years), we observed a 51% (95%CI;75%;9%) lower odds of children scoring not normal for hyperactivity and a decrease of 3.20% (95%CI, −6.01%; −0.30%) in BLC response time, for every IQR increase in fungal Shannon diversity. Contrarily, microbial loads were directly associated with SDQ scales and response time. For example, a 2-fold increase in Gram-positive bacterial load was associated with 70% (95%CI 18%; 156%) higher odds of scoring not normal for hyperactivity and an increase of 5.17% (95%CI 0.87%; 9.65%) in DMS response time. Our findings show that early-life exposure to diverse indoor fungal communities is associated with better behavioral and cognitive outcomes, whereas higher indoor microbial load was associated with worse outcomes.

Background: Plant human microbiome interactions with human health are hypothesized but so far barely investigated. Therefore, we assessed the role of the indoor and gut microbial community on childhood blood pressure, the most predominant modifiable cardiovascular risk factor that tracks over life time.Methods: We investigated whether the bacterial community of indoor ivy plants and the intestinal microbiome were associated with the blood pressure of four-to-six-year-old children enrolled in the longitudinal ENVIRONAGE birth cohort. Ivy plants were placed in family homes for an average of 44 days, after which the blood pressures of resident children were measured according to the European Society of Hypertension guidelines. Besides, a stool sample was taken close to the day of blood pressure measurements. Bacterial communities of 104 plant samples and 78 stool samples were characterized using 16S rRNA gene amplicon sequencing.Findings: Every doubling in observed alpha diversity in the plant samples was associated with 1·63 mmHg (95% CI: 0·01 to 3·25) higher systolic blood pressure (SBP) and a 1·73 mmHg (95% CI: 0·05 to 3·41) higher mean arterial pressure (MAP). In contrast, every interquartile range increment in observed diversity in stool was associated with a 4·50 mmHg (95% CI: -8·77 to -0·23) lower SBP and a 4·40 mmHg (95% CI: -8·84 to 0·03) lower MAP. Furthermore, the relative abundance of Proteobacteria on leaves was positively associated with blood pressure, while Proteobacteria, Firmicutes and Melainabacteria levels in stool were negatively associated. The presence of intestinal Melainabacteria, who are non-photosynthetic Cyanobacteria siblings, indicates an early life plant-human bacterial transfer.Interpretation: We present one of the first studies on plant-human microbiome interactions and show that the indoor plant and intestinal microbial diversity have opposite effects on blood pressure in four-to-six-year-old children.Funding: This research is supported by the EU research council “project ENVIRONAGE” (ERC-2012-StG 310,890), Flemish Scientific Fund (FWO) (G073315N/G048420N) and “Kom op tegen Kanker”. Thessa Van Pee holds a doctoral fellowship of the FWO, grant number: 11C7421N.Declaration of Interest: All authors declare no competing financial nor personal interests.Ethics Approval: Our study was conducted within the ENVIRONAGE birth cohort framework, of which the rationale and full methodology have been described previously. This study complied with the principles outlined in the Helsinki Declaration31 and was approved by the ethics committee of Hasselt University and East-Limburg Hospital (EudraCT B37120107805). All mothers signed a consent form before participation.

Background: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. Objectives: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length. Methods: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment. Results: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 mu g/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity. Conclusions: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.

Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (μg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3–33.9). The mean estimated dose of dietary acrylamide across studies was 23 μg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.

This year marks the 20th anniversary of the discovery of acrylamide in food.In 2002, acrylamide was discovered in common foods, such as coffee, potato crisps and chips, cookies, and several other cereal and potato-based foods prepared at high temperatures (>120 • C) under low-moisture conditions.In 1994, acrylamide was classified as a probable human carcinogen (group 2A) by the International Agency for Research on Cancer (IARC) (1), and it was also known to cause genotoxicity, neurotoxicity, and reproductive and developmental toxicity in animal experiments.In this issue of the American Journal of Clinical Nutrition, Bellicha et al. ( 2) investigated whether dietary acrylamide is associated with an increased breast cancer risk, according to menopausal status and hormone receptor status.They used data from the NutriNet-Santé study, a French, web-based, prospective cohort.Acrylamide exposure was measured by collecting multiple 24-hour dietary records during the first 2 years of the study (on average, 5.5 per participant), and outcomes were ascertained by self-report and validated with linkage to the national health insurance database.Strengths of this study include the measurement of portion sizes, the use of national measurements to estimate acrylamide exposure, the inclusion of a large number of premenopausal cases, and study heterogeneity of associations according to hormone receptor status.A weakness is that hormone receptor status was not uniformly determined.Bellicha et al. ( 2) observed a borderline significant increased risk of breast cancer in women with a high dietary acrylamide intake (HR: 1.21; 95% CI: 1.00, 1.47).The association was stronger in premenopausal women (HR: 1.40; 95% CI: 1.04, 1.88), especially in premenopausal women with hormone receptorpositive breast cancer (estrogen and/or progesterone receptors).These findings are an important contribution to the knowledge regarding the possible carcinogenicity of dietary acrylamide.In 2005, the first formal risk assessment of dietary acrylamide exposure was conducted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (3).The committee concluded that dietary acrylamide exposure may entail a human health concern with regard to cancer, and recommended reduced exposure of the general population.In 2015, the European Food Safety Authority (EFSA) confirmed JECFA's conclusion, and also noted that acrylamide levels in foods were not consistently lower in the years leading up to its risk assessment (4).

The gut microbiome plays an essential role in human health. Despite the link between air pollution exposure and various diseases, its association with the gut microbiome during susceptible life periods remains scarce. In this study, we examined the association between black carbon (BC) particles quantified in pre- and post-natal biological matrices and bacterial richness and diversity measures, and bacterial families. 85 stool samples were collected from four-to-six-year-old children enrolled in the ENVIRONAGE cohort. We performed 16S rRNA gene sequencing to calculate bacterial richness and diversity indices (Chao1 richness, Shannon and Simpson diversity) and the relative abundance of bacterial families. BC particles were quantified via white light generation under femtosecond pulsed laser illumination in placental tissue and cord blood (pre-natal exposure biomarkers), and urine (post-natal exposure biomarker). We used robust multivariable-adjusted linear models to examine the associations between quantified BC loads and richness and diversity measures. Additionally, we performed differential relative abundance analyses of bacterial families while correcting for sampling fraction bias. Results are expressed as percentage change per BC doubling. Two diversity indices were negatively associated with placental BC (Shannon: -4.38%, p=0.04; Simpson: -0.90%, p=0.04), cord blood BC (Shannon: -3.28%, p=0.05; Simpson: -0.91, p=0.02), and urinary BC (Shannon: -3.39%, p=0.0007; Simpson: -0.89%, p<0.0001). The explained variance of BC on the above indices varied from 5.90 to 16.81%. Multi-exposure models showed stronger relationships with urinary BC loads for both indices. Placental BC was negatively associated with the bacterial families Defluviitaleaceae and Marinifilaceae, and urinary BC with Christensenellaceae and Coriobacteriaceae. These results show that BC particles quantified in pre- and post-natal biological matrices may influence the composition and diversity of the childhood intestinal microbiome, addressing the influential role of air pollution exposure during pregnancy and early life on human health. Keywords: gut, microbiome, air pollution, black carbon, pregnancy, early childhood

Little is known about the potential role of indoor plants in shaping the indoor microbiota. Within the ENVIRONAGE birth cohort, we collected settled dust and performed 16S and ITS amplicon sequencing and qPCR measurements to characterize the indoor microbiota, including bacterial and fungal loads and Chao1 richness, Shannon, and Simpson diversity indices. For 155 households, we obtained information on the number of indoor plants. We performed linear regression models adjusted for several a priori chosen covariables. Overall, an increase in indoor plants and density was associated with increased microbial diversity, but not load. For example, we found an increase of 64 (95%CI:3;125) and 26 (95%CI:4;48) units of bacterial and fungal taxa richness, respectively, in households with more than three plants compared to no plants. Our results support the hypothesis that indoor plants can enrich indoor microbial diversity, while impacts on microbial loads are not obvious.

Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.

Introduction: During early childhood, neuronal networks are highly susceptible to environmental factors. Previous research suggests that green space exposure is beneficial for cognitive functioning. Here, we investigate the associations between residential green space exposure and behavioral problems and cognitive development in children aged four to six years. Method: We included children participating in the ENVIRONAGE birth cohort. Residential green spaces were calculated based on high-resolution land cover data within several buffers (50-1,000 m) around the residence. The children's behavior was assessed with the Strengths and Difficulties Questionnaire (SDQ) among 411 children. In addition, to evaluate cognitive function, 456 children completed four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We used multivariate logistic and linear regression models while accounting for potential confounders and covariables. Results: An interquartile (IQR) increase of residential green space within 50 m was associated with a 38% (95% CI: 56;14) lower odds of a child having hyperactivity problems. Additionally, we found a beneficial influence of residential green space in close proximity (50-100 m) on the attention and psychomotor speed, represented by the Motor Screening Task. For example, we found a decrease of 0.45 (95% CI: -0.82;-0.09) pixel units from target center with an IQR increase of residential green space in a 50 m buffer. In addition, we observed an improved visual recognition/working memory, represented by the Delayed Matching to Sample Task within all included buffers (50-1000 m). For example, we observed a decrease of 4.91% (95 %CI: -7.46;-2.36) probability of an error occurring if the previous trial was correct and a 2.02% (95 %CI: 0.08; 3.97) increase of correct trials with an IQR increase of green space within a 100 m buffer. Conclusion: This study provides additional indications for a beneficial influence of green space exposure on the development of behavioral problems and cognitive function as young as four years of age.

ScopeFurfuryl alcohol is a heat‐induced food contaminant, classified as possibly carcinogenic to humans. The proximal carcinogen 2‐sulfoxymethylfuran leads to adduct formation in DNA and proteins (e.g., N‐((furan‐2‐yl)methyl)‐Val (FFA‐Val) in hemoglobin).Methods and resultsThis study analyzed human erythrocyte samples from two studies for the presence of FFA‐Val: the Risks and Benefits of a Vegan Diet study (RBVD; 72 adults) and the ENVIRonmental influence ON early AGEing birth cohort study (ENVIRONAGE; 100 mother‐newborn pairs). In the RBVD study, FFA‐Val levels are lower in vegans compared to omnivores (median 13.0 vs 15.8 pmol g−1 hemoglobin, p = 0.008), and lower in non‐smokers compared to smokers (median 14.1 vs 17.0 pmol g−1 hemoglobin, p = 0.003). In the birth cohort, FFA‐Val levels are distinctly higher in maternal compared to newborn samples (median 15.2 vs 2.2 pmol g−1 hemoglobin, p < 0.001).ConclusionsFFA‐Val, hitherto detected only in blood samples of mice, is quantifiable in all human samples, indicating a general exposure to furfuryl alcohol. The low adduct levels in blood samples from newborn children suggested that the placenta is a barrier to furfuryl alcohol. Dietary habits and tobacco smoking are two main influencing factors on the formation of FFA‐Val, which may be of use as a biomarker of exposure to furfuryl alcohol.

BACKGROUND:The influence of outdoor green space on microbial communities indoors has scarcely been investigated. Here, we study the associations between nearby residential green space and residential indoor microbiota. METHODS:We collected settled dust from 176 living rooms of participants of the ENVIRONAGE birth cohort. We performed 16S and ITS amplicon sequencing, and quantitative PCR measurements of total bacterial and fungal loads to calculate bacterial and fungal diversity measures (Chao1 richness, Shannon and Simpson diversity indices) and relative abundance of individual taxa. Green spaces were estimated within 50m and 100m buffers around the residential address. We defined total residential green space using high-resolution land-cover data, further stratified in low-growing (height<3m) and high-growing green (height>3m). We used land-use data to calculate the residential nature. We ran linear regression models, adjusting for confounders and other potential determinants. Results are expressed as units change for an interquartile range (IQR) increase in residential green space and their 95% confidence intervals (CI). RESULTS:After adjustment, we observed statistically significant associations between the indoor microbial diversity indices and nearby residential green space. For bacteria, the Shannon index was directly associated with residential nature (e.g. 0.08 units increase (CI:0.02,0.13) per IQR increase in nature within a 50m buffer). Fungal diversity was directly associated with high-growing residential green and inversely with low-growing green. For example, an IQR increase in high-growing green within a 50m buffer was associated with increases in 0.14 (CI:0.01,0.27) and 0.02 (CI:0.008,0.04) units in the Shannon and Simpson indices, respectively. CONCLUSIONS:Nearby green space determines the diversity of indoor environment microbiota, and the type of green differently impacts bacterial and fungal diversity. Further research is needed to investigate in more detail possible microbial taxa compositions underlying the observed changes in indoor microbiota diversity and to explore their contribution to beneficial health effects associated with green space exposure.

Background Up to now, 3 epidemiological studies have shown clear inverse associations between prenatal acrylamide exposure and birth size. In addition to studying the association between acrylamide and birth size, we investigated the interaction between acrylamide and polymorphisms in acrylamide-metabolising genes, with the aim of probing the causality of the inverse relationship between acrylamide and fetal growth. Methods We investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels (AA-Hb and GA-Hb) in cord blood) and birth weight, length and head circumference in 443 newborns of the ENVIR ON AGE (ENVIRonmental influence ON AGEing in early life) birth cohort. In addition, we studied interaction with single nucleotide polymorphisms (SNPs) in CYP2E1 , EPHX1 and GSTP1, using multiple linear regression analysis. Results Among all neonates, the body weight, length and head circumference of neonates in the highest quartile was − 101 g (95% CI: − 208, 7; p for trend = 0.12), − 0.13 cm (95% CI: − 0.62, 0.36; p for trend = 0.69) and − 0.41 cm (− 0.80, − 0.01; p for trend = 0.06) lower, respectively, compared to neonates in the lowest quartile of AA-Hb in cord blood, For GA-Hb, the corresponding effect estimates were − 222 g (95% CI: − 337, − 108; p for trend = 0.001), − 0.85 (95% CI: − 1.38, − 0.33; p for trend = 0.02) and − 0.55 (95% CI: − 0.98, − 0.11; p for trend = 0.01), respectively. The associations for GA-Hb were similar or stronger in newborns of non-smoking mothers. There was no statistically significant interaction between acrylamide exposure and the studied genetic variations but there was a trend of stronger inverse associations with birth weight and head circumference among newborns with homozygous wildtypes alleles for the CYP2E1 SNPS and with variant alleles for a GSTP1 SNP (rs1138272). Conclusions Prenatal dietary acrylamide exposure, specifically in the form of its metabolite glycidamide, was inversely associated with birth weight, length and head circumference. The interaction pattern with SNPs in CYP2E1, although not statistically significant, is an indication for the causality of this association. Other studies are needed to corroborate this finding.

INTRODUCTION:Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth.METHODS:In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes.RESULTS:We observed lower cord plasma TSH (-10.2% [95% CI: -15.0, -4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of -2.9% (95% CI: -5.7, -0.1) and -3.9% (95% CI: -6.2, -1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (-11.2% [95% CI: -19.5, -0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight.CONCLUSIONS:A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

BACKGROUND:Glycidol, a probable human carcinogen, is a reactive chemical released in the gastrointestinal tract from glycidyl fatty acid esters, which are heat-induced dietary contaminants.OBJECTIVES:To investigate the prenatal transfer of glycidol, a specific hemoglobin adduct was measured as a biomarker for internal glycidol exposure in paired cord and maternal blood samples.METHODS:In 100 mother-newborn pairs from the Belgian ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we studied the correlation between levels of the glycidol-derived hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val) in paired cord and maternal blood samples. The adduct levels were determined after cleavage with a modified Edman degradation by using ultra-high performance liquid chromatography-tandem mass spectrometry and an isotope-labeled reference standard.RESULTS:2,3-DiHOPr-Val was detectable in all 100 maternal blood samples and in 96 cord blood samples (LOD =0.5 pmol 2,3-diHOPr-Val/g hemoglobin), with medians of 5.4 (range: 2.3-29.2) and 1.6 (range: LOD - 8.9) pmol/g hemoglobin), respectively. In blood samples of mothers who smoked during pregnancy and in the cord blood samples of their newborns (n = 6), the median 2,3-diHOPr-Val levels were 16.7 (range: 6.4-29.2) and 6.2 (range: LOD - 8.6) pmol/g hemoglobin, respectively. The median ratio of 2,3-diHOPr-Val levels of cord to maternal blood was 0.35 (range: 0.19-1.14) (n = 49). The Spearman correlation coefficient between 2,3-diHOPr-Val levels in cord and maternal blood samples was 0.63 (p < 0.001) among all mother-newborn pairs and 0.59 (p < 0.001) among mother-newborn pairs of non-smoking mothers.DISCUSSION:Maternal data confirm widespread exposure to glycidol, also in non-smokers. Neonatal levels indicate prenatal exposure to glycidol, due to an obviously relatively unhindered passive transfer through the placental barrier. Possible health effects of fetal (and postnatal) glycidol exposure in children may be addressed in epidemiological studies.