1,720,969 research outputs found
Microbiome development in early life: the role of environmental exposures in the ENVIRONAGE birth cohort
It is well established that the environment in which we live influences our health. Air pollution exposure has been linked to a higher risk of asthma and inflammatory bowel disorders. In contrast, green space exposure has been associated with lower rates of overweight and improved mental wellbeing. Pregnancy and early childhood are especially critical exposure periods as they represent vulnerable life stages in which the child is in full development. Moreover, exposures during these susceptible periods may have long-lasting health consequences. Nevertheless, there is limited literature on the associations between exposure to air pollution or green space and the microbiome in children.
In Chapter 1, we systematically reviewed all available epidemiological, in vitro, and animal evidence on the association between particulate air pollution exposure and intestinal microbiome composition. Given the lack of studies in healthy children, we studied the association between black carbon particles quantified in placental tissue, cord blood, and urine, as biomarkers of pre- and postnatal particulate air pollution exposure, respectively, and the intestinal microbiome composition in four-to-six-year-old children in Chapter 2A. Chapter 2B further explored this relationship in a study with more participants and more detailed information on potential covariables, such as intestinal transit time and diet. In this larger study, particulate air pollution exposure was modeled during the previous year and stool samples were collected from four-to-twelve-year-old children. As the translocation of air pollution-related particles into the intestines is hypothesized as a potential underlying mechanism, we examined whether particles could be visualized in human ileum and colon biopsies of human donors in Chapter 3. Finally, Chapter 4 studied the impact of another type of environmental exposure, i.e., green space around the residence and school combined, on alpha diversity of the skin microbiome in three-to-twelve-year-old children. The key findings of the doctoral research described in this dissertation are summarized in Table 1. In summary, we found that exposure to particulate air pollution was associated with the richness, evenness, and diversity of the intestinal microbiome and the relative abundance of different bacterial families. We noted that these associations were sex-specific, with negative associations in boys and positive trends in girls. Furthermore, we showed the translocation of air pollution-related particles into intestinal tissue, with a higher load in ileum compared to colon. This translocation provides a mechanism for the observed associations between air pollution exposure and the intestinal microbiome. Lastly, exposure to total green and highgrowing green around the residence and school was positively associated with the skin microbiome richness and the relative abundance of four bacterial families
Microbiome development in early life: the role of environmental exposures in the ENVIRONAGE birth cohort
It is well established that the environment in which we live influences our health. Air pollution exposure has been linked to a higher risk of asthma and inflammatory bowel disorders. In contrast, green space exposure has been associated with lower rates of overweight and improved mental wellbeing. Pregnancy and early childhood are especially critical exposure periods as they represent vulnerable life stages in which the child is in full development. Moreover, exposures during these susceptible periods may have long-lasting health consequences. Nevertheless, there is limited literature on the associations between exposure to air pollution or green space and the microbiome in children.
In Chapter 1, we systematically reviewed all available epidemiological, in vitro, and animal evidence on the association between particulate air pollution exposure and intestinal microbiome composition. Given the lack of studies in healthy children, we studied the association between black carbon particles quantified in placental tissue, cord blood, and urine, as biomarkers of pre- and postnatal particulate air pollution exposure, respectively, and the intestinal microbiome composition in four-to-six-year-old children in Chapter 2A. Chapter 2B further explored this relationship in a study with more participants and more detailed information on potential covariables, such as intestinal transit time and diet. In this larger study, particulate air pollution exposure was modeled during the previous year and stool samples were collected from four-to-twelve-year-old children. As the translocation of air pollution-related particles into the intestines is hypothesized as a potential underlying mechanism, we examined whether particles could be visualized in human ileum and colon biopsies of human donors in Chapter 3. Finally, Chapter 4 studied the impact of another type of environmental exposure, i.e., green space around the residence and school combined, on alpha diversity of the skin microbiome in three-to-twelve-year-old children. The key findings of the doctoral research described in this dissertation are summarized in Table 1. In summary, we found that exposure to particulate air pollution was associated with the richness, evenness, and diversity of the intestinal microbiome and the relative abundance of different bacterial families. We noted that these associations were sex-specific, with negative associations in boys and positive trends in girls. Furthermore, we showed the translocation of air pollution-related particles into intestinal tissue, with a higher load in ileum compared to colon. This translocation provides a mechanism for the observed associations between air pollution exposure and the intestinal microbiome. Lastly, exposure to total green and highgrowing green around the residence and school was positively associated with the skin microbiome richness and the relative abundance of four bacterial families
Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies
Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a gatekeeper between mother and fetus. Knowledge regarding the barrier capacity of the placenta for nanoparticles is limited, mostly due to technical obstacles and ethical issues. We systematically summarize and discuss the current evidence and define knowledge gaps concerning the maternal-fetal transport and fetoplacental accumulation of (ultra)fine particles and nanoparticles. We included 73 studies on placental translocation of particles, of which 21 in vitro/ex vivo studies, 50 animal studies, and 2 human studies on transplacental particle transfer. This systematic review shows that (i) (ultra)fine particles and engineered nanoparticles can bypass the placenta and reach fetal units as observed for all the applied models irrespective of the species origin (i.e., rodent, rabbit, or human) or the complexity (i.e., in vitro, ex vivo, or in vivo), (ii) particle size, particle material, dose, particle dissolution, gestational stage of the model, and surface composition influence maternal-fetal translocation, and (iii) no simple, standardized method for nanoparticle detection and/or quantification in biological matrices is available to date. Existing evidence, research gaps, and perspectives of maternal-fetal particle transfer are highlighted.sponsorship: This work was supported by the Flemish Scientific Research Foundation (FWO) funding granted to EB (1150920 N), TSN and MA (G082317N), and HB (12P6819N). The FWO had no role in the design, conduct, and preparation of the manuscript. (Flemish Scientific Research Foundation (FWO)|1150920 N, Flemish Scientific Research Foundation (FWO)|G082317N, Flemish Scientific Research Foundation (FWO)|12P6819N)status: Publishe
The Gut Microbiome and Residential Surrounding Greenness: a Systematic Review of Epidemiological Evidence
Purpose of Review 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.Recent Findings 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.Thessa Van Pee holds a doctoral fellowship of the Research Foundation Flanders, grant number: 11C7421N
Ambient particulate air pollution and the intestinal microbiome; a systematic review of epidemiological, in vivo and, in vitro studies
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 intesti-nal microbiome. We systematically summarize and discuss all evidence concerning the effect of particulate air pollu-tion 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 system-atic 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 an-imals. Overall, the population-based studies showed a dose-related continuum of short-and long-term ambient partic-ulate air pollution exposure on lower gut diversity and shifts in taxa over the entire life course
Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories
Importance The cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored.
Objective To identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories.
Design, Setting, and Participants This cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023.
Main Outcomes and Measures The outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins.
Results The sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, −237.52 [95% CI, −343.15 to −131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, −342.78 [95% CI, −463.10 to −222.47]; BWR: coefficient, −0.11 [95% CI, −0.14 to −0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, −366.32 [95% CI, −476.66 to −255.97]; BWR: coefficient, −0.11 [95% CI, −0.15 to −0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, −208.75 [95% CI, −305.23 to −112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, −209.27 [95% CI, −295.14 to −123.40]; BWR: coefficient, −0.07 [95% CI, −0.09 to −0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, −1.33 to −0.68 kg) and body mass index z score (coefficients, −0.41 to −0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, −1.98 to −0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight.
Conclusions and Relevance This cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics
Newborn glomerular function and gestational particulate air pollution
Background Nephron number variability may hold significance in the Developmental Origins of Health and Disease hypothesis. We explore the impact of gestational particulate pollution exposure on cord blood cystatin C, a marker for glomerular function, as an indicator for glomerular health at birth. Methods From February 2010 onwards, the ENVIRONAGE cohort includes over 2200 mothers giving birth at the East-Limburg hospital in Genk, Belgium. Mothers without planned caesarean section who are able to fill out a Dutch questionnaire are eligible. Here, we evaluated cord blood cystatin C levels from 1484 mother-child pairs participating in the ENVIRONAGE cohort. We employed multiple linear regression models and distributed lag models to assess the association between cord blood cystatin C and gestational particulate air pollution exposure. Findings Average +/- SD levels of cord blood cystatin C levels amounted to 2.16 +/- 0.35 mg/L. Adjusting for covariates, every 0.5 mu g/m(3) and 5 mu g/m(3) increment in gestational exposure to black carbon (BC) and fine particulate matter (PM2.5) corresponded to increases of 0.04 mg/L (95% CI 0.01-0.07) and 0.07 mg/L (95% CI 0.03-0.11) in cord blood cystatin C levels (p < 0.01), respectively. Third-trimester exposure showed similar associations, with a 0.04 mg/L (95% CI 0.00-0.08) and 0.06 mg/L (95% CI 0.04-0.09) increase for BC and PM2.5 (p < 0.02). No significant associations were observed when considering only the first and second trimester exposure. Interpretation Our findings indicate that particulate air pollution during the entire pregnancy, with the strongest effect sizes from week 27 onwards, may affect newborn kidney function, with potential long-term implications for later health.Funding
Special Research Fund (Bijzonder Onderzoeksfonds, BOF), Flemish Scientific Research Fund (Fonds Wetenschappelijk Onderzoek, FWO), and Methusalem
Acknowledgements
This ENVIRONAGE birth cohort study is supported Methusalum grant and the Flemish Scientific Research Fund (FWO, N1516112/ G087311N10). LR acknowledges funding from the Special Research Fund (Bijzonder Onderzoeksfonds, BOF) for a doctoral fellowship (BOF20DOC15). The authors want to express their greatest gratitude to the participating parents and children, as well as the staff of the maternity ward, the midwives, and the staff of the clinical laboratory of the East-Limburg Hospital in Genk
Relative biodistribution and accumulation of carbonaceous nanoparticles inside the murine and human kidney
Background
Epidemiological and toxicological studies underscore the adverse health effects of combustion-derived particles, such as carbonaceous nanoparticles (CNPs), which translocate to various organs, including the kidneys. Given the kidneys play a crucial role in filtering toxins, CNP accumulation may pose a risk to renal function. We investigated CNP biodistribution in murine and human kidney tissue to assess potential impacts on kidney health.
Methods
In the controlled murine model, wild-type C57BL/6J mice were exposed to CNPs through whole-body exposure. Human kidney tissue was analyzed without prior knowledge of exposure history. CNPs in kidney tissue were detected using femtosecond-pulsed illumination and quantified via a peak-finding algorithm. Renal components – the glomerulus, proximal and distal tubules, and blood vessels – were visualized through immunofluorescence. Colocalization of CNPs with renal structures was quantified using the Just Another Colocalization Plugin. Structural differences were evaluated using Kruskal-Wallis tests.
Results
CNPs were detected in all investigated renal structures of both mouse and human kidneys, providing direct evidence of their translocation. The relative distribution was comparable between species, with no statistically significant differences in colocalization (q > 0.05). The percentages of CNPs in mice vs. humans colocalized with glomeruli (1.46 % vs. 1.91 %), proximal tubules (13.43 % vs. 16.10 %), distal tubules (2.72 % vs. 3.25 %), and blood vessels and capillaries (4.16 % vs. 5.21 %).
Conclusions
Proximal tubules exhibited the highest relative CNP accumulation in both species. This aligns with research linking environmental pollutants, such as black carbon, to decreased tubular kidney function, suggesting proximal tubule involvement in particle processing.the Special Research Fund (BOF) from Hasselt University
the Research Foundation Flanders (FWO)
the European Union’s Horizon 2020
The authors acknowledge funding from the Special Research Fund (BOF) from Hasselt University granted to L.R. (BOF20DOC15) and funding from the Research Foundation Flanders (FWO) granted to K.V. (G059219). Additionally, the animal study was supported by the European Union’s Horizon 2020 research and innovation program under grant agreement No. 814978 (TUBE). BOF nor FWO nor TUBE had no role in the design, conduct, and preparation of the manuscript.
Acknowledgements
The authors wish to thank and acknowledge Mr. J. Boere, Mr. E. Duistermaat, and Mr. P. Fokkens with the assistance and the execution of the exposure experiments. Furthermore, the authors wish to thank Roel P.F. Schins and his colleagues with the assistance in setting up the exposure and feedback. Additionally, the authors wish to acknowledge and thank Mr. R. Braeken for the fixation and paraffin embedding of mouse kidney tissue samples and the AOMC for the microscopy support. The authors wish to thank Ms. J. De Loor for her aid with collection and transportation of kidney biopsy tissue. The authors also thank the centers of the Leuven Collaborative Group for Renal Transplantation, as well as the clinicians, lab technicians, surgeons, nursing staff, and patients in the study
Translocation of black carbon particles to human intestinal tissueResearch in context
Summary: 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
Accumulation of Black Carbon Particles in Placenta, Cord Blood, and Childhood Urine in Association with the Intestinal Microbiome Diversity and Composition in Four- to Six-Year-Old Children in the ENVIRONAGE Birth Cohort
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: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text]); Simpson: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text])], cord blood black carbon [Shannon: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text]); Simpson: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text])], and urinary black carbon [Shannon: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text]); Simpson: [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text])]. 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/EHP1125
- …
