Bibliography Tag: developmental impacts

Rueda-Ruzafa et al., 2019

Rueda-Ruzafa, L., Cruz, F., Roman, P., & Cardona, D.; “Gut microbiota and neurological effects of glyphosate;” NeuroToxicology, 2019, 75, 1-8; DOI: 10.1016/j.neuro.2019.08.006.


There are currently various concerns regarding certain environmental toxins and the possible impact they can have on developmental diseases. Glyphosate (Gly) is the most utilised herbicide in agriculture, although its widespread use is generating controversy in the scientific world because of its probable carcinogenic effect on human cells. Gly performs as an inhibitor of 5-enolpyruvylshikimate-3-phospate synthase (EPSP synthase), not only in plants, but also in bacteria. An inhibiting effect on EPSP synthase from intestinal microbiota has been reported, affecting mainly beneficial bacteria. To the contrary, Clostridium spp. and Salmonella strains are shown to be resistant to Gly. Consequently, researchers have suggested that Gly can cause dysbiosis, a phenomenon which is characterised by an imbalance between beneficial and pathogenic microorganisms. The overgrowth of bacteria such as clostridia generates high levels of noxious metabolites in the brain, which can contribute to the development of neurological deviations. This work reviews the impact of Gly-induced intestinal dysbiosis on the central nervous system, focusing on emotional, neurological and neurodegenerative disorders. A wide variety of factors were investigated in relation to brain-related changes, including highlighting genetic abnormalities, pregnancy-associated problems, diet, infections, vaccines and heavy metals. However, more studies are required to determine the implication of the most internationally used herbicide, Gly, in behavioural disorders. FULL TEXT

Kokroko et al., 2020

Kokroko, J., Kogut, K., Harley, K., & Eskenazi, B.; “Prenatal beta-Hexachlorocyclohexane (beta-HCH) Exposure and 7-Year Child IQ in the CHAMACOS Birth Cohort;” Neurotoxicity Research, 2020, 37(3), 553-563; DOI: 10.1007/s12640-020-00160-w.


Fetal and infant exposures to beta-hexachlorocyclohexane (beta-HCH) occur through placental and breastmilk transfers. No studies have examined the relationship between beta-HCH and child intelligence quotient (IQ). This study examined associations between in utero beta-HCH exposure and cognitive development in 7-year-old children. Data from women and children (n = 256) participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study were evaluated. We assessed exposure to beta-HCH by measuring maternal serum concentration during pregnancy. We administered the Wechsler Intelligence Scale for Children (WISC), Fourth Edition, to children at age 7. Analyses were adjusted for maternal age, country of birth, work status, parity, and other pesticide exposures, language used for child cognitive assessment, and duration of breastfeeding. Higher serum beta-HCH concentrations were associated with higher cognitive scores across all unadjusted models for the full-scale and sub-scale cognitive tests. In the adjusted models, a 10-fold increase in serum beta-HCH concentration was associated with a 4.5-point increase in Working Memory IQ score (95% CI, 0.6 to 8.3; p = 0.02). We observed no significant interaction by length of breastfeeding or sex on associations. Our findings suggest that prenatal exposure to beta-HCH is not adversely related to IQ at age 7 in a cohort of Mexican American children with fairly high exposure in utero as measured by maternal serum levels. Future research must replicate these findings in other study cohorts of women and children.

Kang et al., 2019

Kang, D. W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R.; “Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota;” Scientific Reports, 2019, 9(1), 5821; DOI: 10.1038/s41598-019-42183-0.


Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future. FULL TEXT

Shah and Kingdom, 2011

Shah, Prakesh, & Kingdom, John; “Long-term neurocognitive outcomes of SGA/IUGR infants;” Obstetrics, Gynaecology & Reproductive Medicine, 2011, 21(5), 142-146; DOI: 10.1016/j.ogrm.2011.02.004.


With advances in the management of preterm neonates, the chances of survival have increased even among those who are intrauterine growth restricted (IUGR) or who are born small for gestational age (SGA). However, infants who are IUGR/SGA are considered at higher risk of physical and neurodevelopmental abnormalities, although the reported impacts of IUGR and SGA status at birth on neurodevelopmental outcomes in long-term outcomes studies have varied. In particular, some reports have indicated gradual improvement in neurodevelopmental functions over time in these infants. We have therefore reviewed all the available reports describing neurodevelopmental outcomes of preterm and term SGA infants beyond 5 years of age. Preterm SGA infants are at increased risk of impairment in neuromotor, cognitive, behavioural and scholastic attainments compared with preterm non-SGA infants. On the other hand, term SGA infants had problems in scholastic/vocational attainments compared with term non SGA infants, while adverse neuromotor, cognitive and behavioural outcomes were not consistently observed at higher rates. Limitations regarding the validity of studies of long-term outcomes of SGA infants are discussed and a potential approach is suggested. FULL TEXT

Zhang et al., 2018

Zhang, M., Ma, W., Zhang, J., He, Y., & Wang, J.; “Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China;” Scientific Reports, 2018, 8(1), 13981; DOI: 10.1038/s41598-018-32219-2.


Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared with typical development (TD) children. However, few studies on gut bacteria of children with ASD have been conducted in China. Here, in order to elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated differences in fecal microbiota between 35 children with ASD and 6 TD children. At the phylum level, the fecal microbiota of ASD group indicated a significant increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more abundant in the ASD group whereas the abundance of Veillonella and Streptococcus was decreased significantly compared to the control group. Functional analysis demonstrated that butyrate and lactate producers were less abundant in the ASD group. In addition, we downloaded the association data set of microbe-disease from human microbe-disease association database and constructed a human disease network including ASD using our gut microbiome results. In this microbe-disease network based on microbe similarity of diseases, we found that ASD is positively correlated with periodontal, negatively related to type 1 diabetes. Therefore, these results suggest that microbe-based disease analysis is able to predict novel connection between ASD and other diseases and may play a role in revealing the pathogenesis of ASD. FULL TEXT

Zhang et al., 2020

Zhang, M., Chu, Y., Meng, Q., Ding, R., Shi, X., Wang, Z., He, Y., Zhang, J., Liu, J., Zhang, J., Yu, J., Kang, Y., & Wang, J.; “A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children;” Science Advances, 2020, 6(43); DOI: 10.1126/sciadv.aba3760.


Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy-quasi-paired cohort-and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD. FULL TEXT

Ruden and Grandjean, 2018

Mie, A., Ruden, C., & Grandjean, P.; “Safety of Safety Evaluation of Pesticides: developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl;” Environmental Health, 2018, 17(1), 77; DOI: 10.1186/s12940-018-0421-y.


Authorization of pesticides for market release requires toxicity testing on animals, typically performed by test laboratories on contract with the pesticide producer. The latter provides the results and summary to the regulatory authorities. For the commonly used pesticide chlorpyrifos, an industry-funded toxicity study concludes that no selective effects on neurodevelopment occur even at high exposures. In contrast, the evidence from independent studies points to adverse effects of current exposures on cognitive development in children. We reviewed the industry-funded developmental neurotoxicity test data on chlorpyrifos and the related substance chlorpyrifos-methyl. We noted treatment-related changes in a brain dimension measure for chlorpyrifos at all dose levels tested, although not been reported in the original test summary. We further found issues which inappropriately decrease the ability of the studies to reveal true effects, including a dosage regimen that resulted in too low exposure of the nursing pups for chlorpyrifos and possibly for chlorpyrifos-methyl, and a failure to detect any neurobehavioral effects of lead nitrate used as positive control in the chlorpyrifos study. Our observations thus suggest that conclusions in test reports submitted by the producer may be misleading. This discrepancy affects the ability of regulatory authorities to perform a valid and safe evaluation of these pesticides. The difference between raw data and conclusions in the test reports indicates a potential existence of bias that would require regulatory attention and possible resolution. FULL TEXT

Gillezeau et al., 2020

Gillezeau, C., Lieberman-Cribbin, W., & Taioli, E.; “Update on human exposure to glyphosate, with a complete review of exposure in children;” Environmental Health, 2020, 19(1), 115; DOI: 10.1186/s12940-020-00673-z.


BACKGROUND: Glyphosate, a commonly used pesticide, has been the topic of much debate. The effects of exposure to glyphosate remains a contentious topic. This paper provides an update to the existing literature regarding levels of glyphosate exposure in occupationally exposed individuals and focuses or reviewing all the available published literature regarding glyphosate exposure levels in children.

METHODS: A literature review was conducted and any articles reporting quantifiable exposure levels in humans published since January 2019 (the last published review on glyphosate exposure) were reviewed and data extracted and standardized.

RESULTS: A total of five new studies reporting exposure levels in humans were found including 578 subjects. Two of these studies focused on occupationally exposed individuals while three of them focused on glyphosate exposure levels in children. Given the sparse nature of the new data, previously identified studies on exposure to glyphosate in children were included in our analysis of children’s exposure. The lowest average level of glyphosate exposure reported was 0.28 μg/L and the highest average exposure levels reported was 4.04 μg/L.

CONCLUSION: The literature on glyphosate exposure levels, especially in children, remains limited. Without more data collected in a standardized way, parsing out the potential relationship between glyphosate exposure and disease will not be possible. FULL TEXT

Hantsoo et al., 2019

Hantsoo, L., Jasarevic, E., Criniti, S., McGeehan, B., Tanes, C., Sammel, M. D., Elovitz, M. A., Compher, C., Wu, G., & Epperson, C. N.; “Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy;” Brain, Behavior, and Immunity, 2019, 75, 240-250; DOI: 10.1016/j.bbi.2018.11.005.


BACKGROUND: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women.

METHODS: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34weeks gestation; plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated.

RESULTS: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q=5.7×10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-alpha and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p=0.03) and eicosapentaenoic acid (EPA) (p=0.05).

DISCUSSION: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of omega-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.