In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk.

Wildland–urban interface (WUI) wildfires are increasingly important climate-related exposure events because they burn built infrastructure and can mobilize legacy contaminants in addition to generating smoke. Although the acute respiratory effects of wildfire smoke are well described, persistent internal metal mixtures and their association with pulmonary function after WUI disasters remain poorly characterized. Using the August 2023 Maui wildfires as a sentinel model, we evaluated 1,400 adults enrolled 6 to 18 mo after the disaster in a community-engaged cohort. We measured 24 urinary metals and assessed pulmonary function by standardized spirometry at the same visit, enabling paired exposure-response analyses. Compared with US reference levels, participants exhibited elevated internal metal burdens, including antimony (40-fold), manganese (3.8-fold), barium (2.3-fold), and arsenic (2.2-fold), with the highest concentrations clustering in the most affected regions. Across three complementary mixture-modeling approaches, higher cumulative metal burden was consistently associated with greater odds of abnormal spirometry. In weighted quantile sum models, each 1-quantile increase in the positive mixture index, driven primarily by arsenic, cadmium, and copper, was associated with higher odds of FVC, FEV ₁ , FEV ₁ /FVC, and FEF _25–75 below the lower limit of normal (odds ratio [OR], 1.71, 1.53, 1.83, and 1.84, respectively). These findings suggest that WUI disasters may generate persistent internal metal mixtures associated with pulmonary impairment months after the event and that air monitoring alone may underestimate the longer-term internal toxic burden following climate-amplified WUI disasters.