Environmental pollutant exposure associated with altered early-life gut microbiome: Results from a birth cohort study

Naspolini, Nathalia Ferrazzo; Meyer, Armando; Moreira, Josino Costa; Sun, Haipeng; Asmus, Carmen Ildes Rodrigues Fróes; Domínguez-Bello, María Gloria

doi:10.1016/j.envres.2021.112545

Cited by 25 publications

(13 citation statements)

References 39 publications

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“…Our finding that PFOS was associated with more diversity, especially among first-born infants or those who were fed exclusively human milk is similar to that of Naspolini et al, who described a positive association between cord blood PFAS concentrations (nonmolar sum of PFOS and PFOA) and gut bacterial diversity in samples from the first-, third-, and sixth-month postpartum in a Brazilian cohort. 15 As in our study, their results were stronger among infants exclusively fed human milk. While different exposure assessment methods were used in our studies, cord blood and milk PFAS concentrations are likely correlated, as evidenced by strong correlations between maternal plasma PFAS and milk PFAS concentrations.…”

Section: Discussionsupporting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

“…Feeding mode and proportion of meals that were human milk are the source of exposure under investigation and therefore only considered in sensitivity analyses for comparability to prior studies. 14,15 We hypothesized that the associations between milk PFAS concentrations and features of the gut microbiome may differ based on underlying characteristics; thus, we conducted stratified analyses to examine possible effect modification in both complete cases and multiply imputed datasets. Stratifying variables included child's sex-a known modifier of health effects due to environmental exposures 33 ; delivery mode-which is a strong driver of the early-life gut microbiome, 20,34 including microbial susceptibility to environmental exposures 22,35 ; and feeding status and parity-both of which are related to PFAS concentrations in milk (i.e., multiparous mothers, who excreted PFAS to a prior fetus, are expected to have lower concentrations of PFAS for the index participant; mothers who feed their infant exclusively human milk excrete more PFAS than those who supplement with formula, and thus are expected to have lower milk PFAS concentrations by 6 weeks postpartum).…”

Section: Statistical Approachmentioning

confidence: 99%

“…12,13 Two prior studies have examined the relationship between early-life exposure to PFAS and the infant gut microbiome, including one study that quantified PFAS exposure in human milk. 14,15 These studies utilized 16S rRNA sequencing, which limits the ability to examine bacterial species and gene pathways. 16 Additionally, underlying characteristics of the study populations (i.e., high proportion of operative births in Brazil and high proportion of preterm births in Norway) necessitate further inquiry in other populations.…”

Section: Introductionmentioning

confidence: 99%

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Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition

Laue

Moroishi

Palys

et al. 2022

Environmental Epidemiology

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Background: Human milk is rich in essential nutrients and immune-activating compounds but is also a source of toxicants including per- and polyfluoroalkyl substances (PFAS). Evidence suggests that immune-related effects of PFAS may, in part, be due to alterations of the microbiome. We aimed to identify the association between milk PFAS exposure and the infant gut microbiome. Methods: PFAS [perfluorooctane sulfonic acid (PFOS) and perfluorooctanoate (PFOA)] were quantified in milk from ~6 weeks postpartum using high-performance liquid chromatography with tandem mass spectrometry. A molar sum (ΣPFAS) was calculated. Caregivers collected infant stool samples at 6 weeks (n = 116) and/or 1 year postpartum (n = 119). Stool DNA underwent metagenomic sequencing. We estimated the association of PFAS with diversity and relative abundances of species with linear regression. Single- and multi-PFAS models adjusted for potential confounders in complete case analyses and with imputed missing covariate data for 6-week and 1-year microbiomes separately. We assessed sensitive populations with stratification. Results: PFOS and PFOA were detected in 94% and 83% of milk samples, respectively. PFOS was associated with increased diversity at 6 weeks among infants fed exclusively human milk [β = 0.24 per PFOS doubling, (95% CI = 0.03, 0.45), P = 0.03] and born to primiparous mothers [β = 0.37 (0.06, 0.67), P = 0.02]. Estimates were strongest in multi-PFAS models and among complete cases. ΣPFAS was associated with Bacteroides vulgatus relative abundance at 1 year [(β = –2.34% per doubling (–3.63, –1.05), FDR q = 0.099]. Conclusions: PFAS may increase infant gut microbiome diversity and alter the relative abundance of biologically relevant bacteria. Additional analyses may identify related health outcomes.

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Section: Discussionsupporting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Statistical Approachmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition

Laue

Moroishi

Palys

et al. 2022

Environmental Epidemiology

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“…Brazil is one of the leading agricultural pesticide-consuming countries in the world (1). The extensive use of pesticides raises concerns about human health (2). Since 2008, Brazil has become the world's top pesticide importer, with more than 1,400 formulations authorized by the government legislation (3).…”

Section: Introductionmentioning

confidence: 99%

Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides

et al. 2022

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Homologous recombination is a crucial pathway that is specialized in repairing double-strand breaks; thus, alterations in genes of this pathway may lead to loss of genomic stability and cell growth suppression. Pesticide exposure potentially increases cancer risk through several mechanisms, such as the genotoxicity caused by chronic exposure, leading to gene alteration. To analyze this hypothesis, we investigated if breast cancer patients exposed to pesticides present a different mutational pattern in genes related to homologous recombination (BRCA1, BRCA2, PALB2, and RAD51D) and damage-response (TP53) concerning unexposed patients. We performed multiplex PCR-based assays and next-generation sequencing (NGS) of all coding regions and flanking splicing sites of BRCA1, BRCA2, PALB2, TP53, and RAD51D in 158 unpaired tumor samples from breast cancer patients on MiSeq (Illumina) platform. We found that exposed patients had tumors with more pathogenic and likely pathogenic variants than unexposed patients (p = 0.017). In general, tumors that harbored a pathogenic or likely pathogenic variant had a higher mutational burden (p < 0.001). We also observed that breast cancer patients exposed to pesticides had a higher mutational burden when diagnosed before 50 years old (p = 0.00978) and/or when carrying BRCA1 (p = 0.0138), BRCA2 (p = 0.0366), and/or PALB2 (p = 0.00058) variants, a result not found in the unexposed group. Our results show that pesticide exposure impacts the tumor mutational landscape and could be associated with the carcinogenesis process, therapy response, and disease progression. Further studies should increase the observation period in exposed patients to better evaluate the impact of these findings.

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Influence of the Microbiota on the Development and Function of the “Second Brain”—The Enteric Nervous System

Green,

Ratcliffe

2024

The Gut-Brain Axis

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Environmental pollutant exposure associated with altered early-life gut microbiome: Results from a birth cohort study

Cited by 25 publications

References 39 publications

Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition

Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition

Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides

Influence of the Microbiota on the Development and Function of the “Second Brain”—The Enteric Nervous System

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