Project description:The objectives of this study were to establish a microbiome profile for oral epithelial dysplasia using archival lesion swab samples to characterize the community variations and the functional potential of the microbiome using 16S rRNA gene sequencing
Project description:Tolerance to dietary antigens is critical to avoid deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens is poorly understood. Here we demonstrate that the goblet cell-derived resistin-like molecule beta (RELMb) is a critical regulator of oral tolerance. We find that RELMb is abundant in serum in both food allergic patients and mouse models of FA. Deletion of RELMβ protects mice from FA, development of food antigen specific IgE and anaphylaxis. RELMb disrupts food tolerance through modulation of the gut microbiome by suppressing gut Lactobacilli. Tolerance is maintained via local production of indole derivatives driving FA protective RORgt+ regulatory T (Treg) cells via activation of the aryl hydrocarbon receptor (AhR). RELMb antagonism in the peri-weaning period restored oral tolerance and protected genetically prone offspring from developing FA later in life. Together, our data identify RELMb as mediating both a novel gut immune-epithelial circuit regulating tolerance to food antigens, a new mode of innate control of antigen specific adaptive immunity via microbiome editing and targetable candidates in this circuit for prevention and treatment of FA.
Project description:Prescription opioids such as oxycodone have been widely used in the United States and have contributed to the ongoing opioid epidemic. While many individuals limit use to prescribed contexts, a subset transitions to misuse and, in some cases, to illicit opioid use. Identifying behavioral and biological factors that predict this vulnerability is critical for improving prevention and intervention strategies. Here, we investigated whether individual differences in behavioral flexibility and gut microbiome composition are associated with future oxycodone intake using a translationally relevant model of oral oxycodone self-administration in male and female Long-Evans rats. We established a model in which distinct intake phenotypes emerged, characterized by animals with high versus low oxycodone consumption. Behavioral flexibility, assessed using a contingency degradation task, was associated with oxycodone intake, identifying it as a potential behavioral biomarker of vulnerability. In parallel, oral oxycodone exposure altered gut microbiome composition, and microbiome features were associated with both behavioral flexibility and drug-taking behavior. These findings support a framework in which individual differences in opioid intake arise from the interaction of pre-existing behavioral traits and biological states, including gut microbiome composition which provides a foundation for identifying predictive biomarkers and developing individualized strategies to mitigate risk for opioid misuse.