A229 GUT MICROBIOTA PROFILES, DIET AND SHORT-CHAIN FATTY ACIDS AS PREDICTORS OF GENERALIZED ANXIETY DISORDER

Abstract Background Generalized anxiety disorder (GAD) is a debilitating chronic condition with a lifetime prevalence of 4–7% worldwide. Both diet and gut microbiota have been previously associated with anxiety. Aims To investigate whether bacterial taxa and/or nutrients associate with GAD, and whether they differ from those of healthy controls (HC). Methods Patients with GAD (n=82) and matched HC (n=97) were assessed by validated questionnaires for anxiety (DASS-21), gastrointestinal (GI) symptoms (Rome III, Short-Form Leeds Dyspepsia), and dietary profiles by the Dietary Questionnaire for Epidemiological Studies. We quantified several blood and stool biomarkers, including inflammatory and neuroactive metabolites, as well as short-chain fatty acids. Stool microbiota profiles were assessed by16S rRNA gene sequencing through Illumina. The data was then analyzed following the pipelines of dada2 and by multiple factor analysis (MFA), mean comparisons, correlation, LEfSe and XGBoost using R software (v.1.2.1335). Multiple comparison results were corrected allowing 5% of FDR. Results Using MFA to analyze all variables, we identified 3 clusters: one mainly composed of HC (n=99, 91% HC, GI symptoms in 25% of subjects), a second mixed cluster (n=30, 80% GAD, GI symptoms in 80%) and a third cluster mainly composed of GAD patients (n=50, 98% GAD, GI symptoms in 86%). When focusing only on the HCs of cluster 1 (n=90) and GADs of cluster 3 (n=49), we found higher GI symptoms, body mass index, serum C-reactive protein and stool calprotectin levels (adj. p=1.3x10-9, 0.001, 0.017 and 0.017, respectively) and lower concentrations of propionate, butyrate and acetate in GAD compared to HC. GADs also reported overall lower caloric intake (kJ/day; adj. p=1.7x10-4) in the food frequency questionnaire. Fibre (g/day) was the macronutrient most negatively associated with anxiety scores (R=-0.44; adj. p=4.2x10-5). Bacteroides was the only bacterial taxon significantly associated with GAD, as well as with anxiety scores (R=0.31, adj. p=0.003). Interestingly, Bacteroides/fiber ratio was strongly correlated to anxiety scores (R=0.58, adj. p=2.7x10-09). Furthermore, demographic, biomarkers and bacterial taxa data were predictive of the patients’ disease state with 92.8% accuracy. The features that aid the model to predict disease state were Bacteroides/fiber ratio, GI symptoms and stool acetate levels. Conclusions Our results suggest that most GAD patients differ in dietary and microbiota profiles from HCs, and that the Bacteroides/fiber ratio, stool acetate and GI symptoms might be good predictors of disease state. Furthermore, these data strongly support the role of microbiota-gut-brain axis in genesis of psychiatric diseases, and they will inform mechanistic studies in gnotobiotic mouse models. Funding Agencies NIH

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