Maternal immune activation (MIA) has been identified as a causal factor in psychiatric disorders by epidemiological studies in humans and mechanistic studies in rodent models. Addressing this gap in species between mice and human will accelerate the understanding of the role of MIA in the etiology of psychiatric disorders. Here, we provide the first study of MIA in the ferret (Mustela putorius furo), an animal model with a rich history of developmental investigations due to the similarities in developmental programs and cortical organization with primates. We found that after MIA by injection of PolyIC in the pregnant mother animal, the adult offspring exhibited reduced social behavior, less eye contact with humans, decreased recognition memory, a sex-specific increase in amphetamine-induced hyperlocomotion, and altered gut microbiome. We also studied the neurophysiological properties of the MIA ferrets in development by in-vivo recordings of the local field potential (LFP) from visual cortex in five- to six-week-old animals, and found that the spontaneous and sensory-evoked LFP had decreased power, especially in the gamma frequency band. Overall, our results provide the first evidence for the detrimental effect of MIA in ferrets and support the use of the ferret as an intermediate model species for the study of disorders with neurodevelopmental origin.

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Background: Increasing evidence suggests a causal relationship between the gut microbiome and psychiatric illnesses. In particular, autism spectrum disorder is associated with gastrointestinal symptoms and alterations in the gut microbiome. Administration of probiotics is a commonly used strategy by caregivers of people with neurodevelopmental illness. However, evidence for successful improvement in gut microbiome and (behavioral) symptoms has been lacking. Results: Here, we use a novel ferret model of maternal immune activation to show that high-dose probiotic administration in a placebo-controlled study design causes changes in the gut microbiome in the form of a transient increase in the administered bacterial species. In contrast, we found no differences in baseline microbiome composition or changes induced by probiotic administration between animals exposed in utero to maternal immune activation and control animals. However, the relative presence of several bacterial species correlated with an increased preference for novelty (object and conspecific). Intriguingly, several of the hits in this screen are species that have previously emerged in the literature as being associated with autism and anxiety. Conclusions: Together, our results suggest that high-dose probiotic interventions may be beneficial for the adjunct treatment of psychiatric illnesses. Placebo-controlled clinical trials in humans are urgently needed.

Aims The ketogenic diet (KD) is standard-of-care to achieve myocardial glucose suppression (MGS) for assessing inflammation using fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET). As KD protocols remain highly variable between centres (including estimation of nutrient intake by dietary logs for adequacy of dietary preparation), we aimed to assess the predictive utility of nutrient intake in achieving MGS. Methods and results Nineteen healthy participants underwent short-term KD, with FDG-PET performed after 1 and 3 days of KD (goal carbohydrate intake <20 g/day). Nutrient consumption was estimated from dietary logs using nutrition research software. The area under receiver operating characteristics (AUROC) of macronutrients (carbohydrate, fat, and protein intake) for predicting MGS was analysed. The association between 133 nutrients and 4 biomarkers [beta-hydroxybutyrate (BHB), non-esterified fatty acids, insulin, and glucagon] with myocardial glucose uptake was assessed using mixed effects regression with false discovery rate (FDR) correction. Median (25th–75th percentile) age was 29 (25–34) years, 47% were women, and 42% were non-white. Median (25th–75th percentile) carbohydrate intake (g) was 18.7 (13.1-30.7), 16.9 (10.4-28.7), and 21.1 (16.6-29.0) on Days 1–3. No macronutrient intake (carbohydrate, fat, or protein) predicted MGS (c-statistic 0.45, 0.53, 0.47, respectively). Of 133 nutrients and 4 biomarkers, only BHB was associated with myocardial glucose uptake after FDR correction (corrected P-value 0.003). Conclusions During highly supervised, short-term KD, approximately half of patients meet strict carbohydrate goals. Yet, in healthy volunteers, dietary review does not provide reassurance for adequacy of myocardial preparation since no clear thresholds for carbohydrate or fat intake reliably predict MGS.