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Kasschau, K. D.

Publications and source records attributed to Kasschau, K. D..

3 recordsLinked to original sources

Polycyclic aromatic hydrocarbons, gut microbiome composition, impulsivity, and attention covary in a human cohort

Polycyclic aromatic hydrocarbons (PAHs) are pervasive environmental pollutants linked to adverse neurobehavioral outcomes, yet the biological pathways coupling exposure to behavior are poorly defined. The gut microbiome is both sensitive to PAH exposure and a modulator of central nervous system function, suggesting it may mediate how PAH exposure influences neurobehavior. We tested whether PAH exposure, gut microbiome composition, and neurobehavioral function covary in a statewide sample of 34 adults stratified into high-impulsivity/poor-attention (HH) and low-impulsivity/fast-attention (LL) groups. Participants provided fecal samples for 16S rRNA profiling and wore silicone wristbands for 30 days to passively sample PAH exposure. Higher PAH exposure associated with HH group membership in a sex-dependent manner, with the largest elevations among HH males. At the community level, PAH exposure profiles correlated with microbiome dissimilarity, and HH membership associated with increased alpha-diversity and altered community composition relative to LL members. At the taxon level, 21 genera were significantly associated with 14 PAH compounds (FDR < 0.1). No individual genera were significantly associated with neurobehavioral group after multiple testing correction. Nevertheless, cross-referencing PAH-responsive genera (FDR < 0.1) against those with nominal neurobehavioral associations (p < 0.05) identified two candidate genera, Hydrogenoanaerobacterium and Methanobrevibacter, whose abundance covaries with both PAH exposure and neurobehavioral phenotype. Both have been independently linked to cognitive or neurological outcomes in prior work. These findings support a three-way relationship among environmental chemical exposure, gut microbiome composition, and neurobehavioral function, establishing an empirical foundation for testing microbiome-mediated links between PAH exposure and neurobehavioral outcomes. IMPORTANCEPAH exposure is widespread and associates with impulsivity and attention problems, but how exposure translates into neurobehavioral risk is unclear. The gut microbiome is a plausible intermediary: gut microbes biotransform environmental chemicals and produce metabolites that influence brain function. In a statewide adult cohort, we show that higher PAH exposure tracks with greater impulsivity and poorer attention in a sex-dependent manner, and that both PAH exposure and neurobehavioral phenotype associate with distinct gut microbiome features at the community and taxon levels. We identify candidate genera at the intersection of PAH exposure and neurobehavioral group whose biology independently implicates them in cognitive and neurological function. By demonstrating that all three domains covary within a single human cohort, this work moves beyond pairwise associations to identify candidate microbial intermediaries for mechanistic investigation. Defining the microbiome constituents that respond to PAH exposure and co-associate with neurobehavioral phenotypes creates opportunities to test microbiome-targeted or exposure-reduction strategies for mitigating PAH-related neurobehavioral impacts.

microbiology↗

Modelling the zebrafish gut microbiome's resistance and sensitivity to climate change and parasite infection

As climate change increases global water temperatures, ecologists expect intestinal helminth infection ranges to expand and increase the health burden on aquatic organisms. However, the gut microbiome can interact with these parasites to influence infection outcomes, raising the possibility that its response to increasing temperatures may help buffer against increased infection burden. To evaluate this hypothesis, we sought to determine if the microbiome is resistant or resilient to the stressors of increased water temperature, helminth exposure, and their combination, and whether this variation linked to infection outcomes. We leveraged the zebrafish (Danio rerio) model organism to measure how these variables relate to the temporal dynamics of the gut microbiome. In particular, we exposed adult zebrafish to the parasitic whipworm Pseudocapillaria tomentosa across three different water temperatures (28{degrees}C, 32{degrees}C, 35{degrees}C), and analyzed fecal microbiome samples at five time points across 42 days. Our findings show that parasite exposure and water temperature independently alter gut microbiome diversity. Moreover, we find that water temperature moderates the association between parasite infection and the gut microbiome. Consistent with this observation, but at odds with current expectations, we find that increasing water temperature reduces parasitic infection in fish. Overall, our results indicate that water temperature alters the contextual landscape of the gut microbiome to impact its response to an exogenous stressor of an intestinal parasite in zebrafish. Furthermore, our findings represent the first report of the effects of elevated temperature on parasitic nematode development in a fish host. Importantly, our study demonstrates that climate change may have unanticipated and environmentally contingent impacts to vertebrate gut microbiomes and health outcomes in response to an exogenous stressor.

microbiology↗

Clearing the air on pollutant disruptions of the gut-brain axis: Developmental exposure to Benzopyrene disturbs zebrafish behavior and the gut microbiome in adults and subsequent generations

Developmental exposure to benzo[a]pyrene (BaP), a ubiquitous environmental pollutant, has been linked to various toxic effects, including neurodegenerative disorders and, most recently, multigenerational behavioral impairment. While the specific mechanisms driving BaP neurotoxicity are not fully understood, recent work highlights two important determinants of developmental BaP neurotoxicity: (1) the aryl hydrocarbon receptor (AHR), which is responsible for inducing host metabolism of BaP, and (2) the gut microbiome, which may interact with BaP to affect its metabolism, or be perturbed directly by BaP to yield disruptions to the gut-brain axis. To explore the role of AHR, the gut microbiome, and their interaction on BaP-induced neurotoxicity, we utilized the zebrafish model. We sought to determine (1) how exposure to BaP and developmental expression of AHR2, a key gene in the zebrafish AHR pathway, link to adult zebrafish behavior, (2) how these same variables associated with the structure and function of the adult zebrafish gut metagenome, and (3) whether these associations were multigenerational. This finding revealed a reticulated axis of association between BaP exposure, developmental AHR2 expression, the zebrafish gut metagenome, and behavior. Our results also indicate that AHR2 is a key mediator of how BaP elicits neurotoxicity and microbiome dysbiosis. Additionally, this axis of association manifests inter- and transgenerationally, suggesting that exposure to BaP may yield dysbiotic and neurodevelopmental impacts on subsequent generations. These findings demonstrate the power of utilizing the zebrafish model to study pollutant-metagenome interactions and elucidate the role of specific host genes in the neurotoxicity and dysbiosis. ImportanceBenzo[a]pyrene (BaP) is a toxic chemical that is especially ubiquitous in industrialized nations, as it is produced in large quantities by burning coal, oil, and other organic compounds. Early-life and in utero exposure to this chemical can induce adverse behavior changes in model animals, like mice and zebrafish. In humans, developmental exposure is linked to symptoms of ADHD, anxiety, and depression. This study found BaP affects zebrafish behavior and the gut microbiome throughout their life and across subsequent generations. We further discovered that a host regulatory pathway called the aryl hydrocarbon receptor is a key component of how benzo[a]pyrene, the gut microbiome, and behavior interconnect. The aryl hydrocarbon receptor binds many toxicants, as well as microbial metabolites associated with maintaining gut homeostasis, and regulates the gut-brain connection. This receptor presents a new potential mechanism of how gut microbiota relate to BaP exposure and behavior for future studies to investigate.

microbiology↗