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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Introduction: Hospitalizations during the coronavirus 2019 (COVID-19) pandemic peaked in New York in March–April 2020. In the months following, emergency department (ED) volumes declined. Our objective in this study was to examine the effect of this decline on the procedural experience of emergency medicine (EM) residents compared to the pre-pandemic period.Methods: We conducted this multicenter, retrospective cohort study of patients seen and key procedures performed by EM residents at hospitals spanning three Accreditation Committee for Graduate Medical Education-approved EM residencies in New York City and Nassau County, NY. We obtained numbers of procedures performed during May–July 2020 and compared them to the same time period for 2019 and 2018. We a priori classified critical care procedures—cardioversion, central lines, chest tubes, procedural sedation, and endotracheal intubation. We also studied “fast-track” procedures—fracture/joint reduction, incision and drainage (I&D), laceration repairs, and splints.Results: Total number of critical care procedures in the months following the COVID-19 peak decreased from 694 to 606 (−12.7%, 95% confidence interval [CI] 10.3–15.4%), compared to an increase from 642 to 694 (+8.1%, 95% CI 6.1–10.5%) the previous year (difference −9.3%). Total number of fast-track procedures decreased from 5,253 to 3,369 (−35.9%, 95% CI 34.6–37.2%), compared to a decrease from 5,333 to 5,253 (−1.5%, 95% CI 1.2–1.9%) the year before (difference −36.3%). Specific critical care procedures performed in 2020 compared to the mean of 2019 and 2018 as follows: cardioversion −33.3%; central lines +19.0%; chest tubes −27.9%; procedural sedation −30.8%; endotracheal intubation −13.8%. Specific fast-track procedures: reductions +33.3%; I&D −48.6%; laceration repair −17.3%; and splint application −49.8%.Conclusion: Emergency medicine residents’ critical and fast-track procedural experience at five hospitals was reduced during the months following the COVID-19 peak in comparison to a similar period in the two years prior. Training programs may consider increasing simulation-lab and cadaver-lab experiences, as well as ED and critical care rotations for their residents to offset this trend.

Nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in the US, partly due to the increasing incidence of metabolic syndrome, obesity, and type 2 diabetes. The roles of bile acids and their receptors, such as the nuclear receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, on the development of NASH are not fully clear. C57BL/6J male mice fed a Western diet (WD) develop characteristics of NASH, allowing determination of the effects of FXR and TGR5 agonists on this disease. Here we show that the FXR-TGR5 dual agonist INT-767 prevents progression of WD-induced hepatic steatosis, inflammation, and fibrosis, as determined by histological and biochemical assays and novel label-free microscopy imaging techniques, including third harmonic generation, second harmonic generation, and fluorescence lifetime imaging microscopy. Furthermore, we show INT-767 decreases liver fatty acid synthesis and fatty acid and cholesterol uptake, as well as liver inflammation. INT-767 markedly changed bile acid composition in the liver and intestine, leading to notable decreases in the hydrophobicity index of bile acids, known to limit cholesterol and lipid absorption. In addition, INT-767 upregulated expression of liver p-AMPK, SIRT1, PGC-1α, and SIRT3, which are master regulators of mitochondrial function. Finally, we found INT-767 treatment reduced WD-induced dysbiosis of gut microbiota. Interestingly, the effects of INT-767 in attenuating NASH were absent in FXR-null mice, but still present in TGR5-null mice. Our findings support treatment and prevention protocols with the dual FXR-TGR5 agonist INT-767 arrest progression of WD-induced NASH in mice mediated by FXR-dependent, TGR5-independent mechanisms.