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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Infants under double attack. Exposures to environmental toxicants, and the modifying role of gut microbiota, for neuropsychological function

Awarded: NOK 6.1 mill.

The aim of this project is to gain knowledge of the effect of toxicants on child cognition and behavioral disorders. We have studied early-life exposure to more than 25 environmental chemicals and neuropsychological development. We have applied state-of-the art multi-pollutant statistical methods to address the analysis of chemical mixtures, and mitigate co-exposure confounding bias. In one paper, we found that DDT was clearly associated with behavioral problems at 1 year of age (Forns et al. Env Research. 2016). Although DDT has been banned in Europe, it continues to persist in the environment and in human foods and bodies. In contrast, perfluorinated compounds which are used in household products like non-stick pans and raincoats, were not associated with psychomotor, cognitive, or behavioral development by 2 years of age in our study (Forns et al. Environ Int. 2015). We have also studied attention-deficit/hyperactivity disorder (ADHD). In two large, pooled analyses of 10 European birth cohorts of nearly 5000 mother-child pairs, information was available on PCB159, HCB, DDE and perfluoroalkyl substances (PFASs or PFCs). Furthermore, we also used our own cohort HUMIS, where a much larger amount of chemicals have been measured, to study ADHD . We identified several toxicants associated with ADHD in children (Lenters V. Environ Int. 2019). We have a paper ready for submission where we identify one chemical associated with autism, where we included an experimental study to verify that the chemical in question affects brain development (Desalegn A et al, in prep). Finally, a novel part of this project has been to measure arsenic species and arsenolipids in breast milk. Arsenic and mercury are transformed by bacteria into forms that may be more toxic than the parent compound as well as more commonly assessed methylmercury. This is the first study in the world to measure arsenic species in human breast milk. Our partners in Graz developed new methods in order to measure these. We have identified novel speciations of arsenic in human milk including some which can cross the blood brain barrier and are of special concern. We are now studying whether they are associated with cognition and behavior. In addition, we have studied interactions between early-life exposure to environmental chemicals and the gut microbiota composition, diversity, and functional metabolites. This is the first study in humans to have done so (Iszatt N, Microbiome 2019). We found that chemicals in human milk did affect the microbial functioning of the gut microbiota substantially, the effects unknown. The perfluorinated chemicals had marked and partly opposing effects and are worth further study. The Illumina sequencing of the mice samples are finished and the metabolomics analysis are ongoing after delays and some analytical problems encountered by our US partners. The conference we planned was successfully held in June 2018 and due to its popularity a new similar conference held in September 2019.

The aim was to gain knowledge of the effect of persistent toxicants on childrens neurodevelopment. We studied early-life exposure to more than 25 environmental chemicals. DDT, even 40 years after it was banned, continues to affect childrens neurodevelopment, increasing behavioral problems. This shows the potential long term consequences of introducing chemicals with persistent properties and calls for new legislation regulating the introduction of chemicals with bioaccumulation properties. Our findings of association between PFAS and neurodevelopment is novel, also the enhanced sensitivity of girls, and would be an argument for forbidding the use of any related perfluorinated compound until proven safe. Another concern relating to the perfluorinated compounds is the large effect we observed on the gut microbiome composition and functionality, with likely health consequences. Special concern has to be given to girls, who seems to be more sensitive than boys.

We aim to increase our knowledge of the associations between environmental toxicants and neuropsychological development in children, while further supplementing the literature by considering associations with gut microbiota (GM). GM variation affects the formation of bioactive compounds and overall fate of toxicants in the body, and is therefore essential in understanding individual susceptibility and improving risk assessments. Furthermore, GM composition and microbial functions will be studied as risk factors for neuropsychological development. We will utilize a unique birth cohort, containing data on both environmental toxicants and GM in early life, where the children are now 8 years old. Data on neuropsychological disorders (including ADHD) have bee n obtained from the Norwegian patient registry. The project will focus on the toxicants PCB, mercury, and arsenic. We aim at improved risk estimates by using a new and more accurate model for postnatal exposure assessment, separate assessment of organic and inorganic forms of metals, controlling for individual susceptibility (due to GM), and assessing chemical interactions. This proposal will take advantage of, and extend, an ongoing EU project (DENAMIC) which studies associations between environmental t oxicants and ADHD. It also supplements ongoing work on GM and obesity (FrimedBio), and POPs and obesity (EU project OBELIX), that will be continued (NFR grant on the same topic). We will collaborate with experimental researchers to validate our findings i n animal models. This proposal will enable future studies on many health outcomes, including neurodegenerative disorders in the mothers. This proposal addresses large public health issues, expands on an already established network of multidisciplinary, hi ghly renowned national and international scientists, and uses longitudinal cohorts, existing biobanks, and national registries. We expect our findings will lead to cutting edge knowledge and high-impact publicati

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering