Alterations in Vagal Tone Are Associated with Changes in the Gut Microbiota of Adults with Anxiety and Depression Symptoms: Analysis of Fecal Metabolite Profiles Author: Laura Pasqualette1,2, Tatiana Kelly da Silva Fidalgo3, Liana Bastos Freitas-Fernandes4, Gabriela Guerra Leal Souza5, Luís Aureliano Imbiriba6, Leandro Araujo Lobo1, Eliane Volchan7, Regina Maria Cavalcanti Pilotto Domingues1, Ana Paula Valente4, Karla Rodrigues Miranda1 Affiliation: <sup>1</sup> Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. <sup>2</sup> Developmental and Educational Psychology, University of Bremen, 28359 Bremen, Germany. <sup>3</sup> Pediatric Dentistry, Department of Preventive and Community Dentistry, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil. <sup>4</sup> National Centre of Nuclear Magnetic Resonance/CENABIO, Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. <sup>5</sup> Laboratory of Psychophysiology, Department of Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35400-000, Brazil. <sup>6</sup> School of Physical Education and Sports, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, Brazil. <sup>7</sup> Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Conference/Journal: Metabolites Date published: 2024 Aug 15 Other: Volume ID: 14 , Issue ID: 8 , Pages: 450 , Special Notes: doi: 10.3390/metabo14080450. , Word Count: 247 Accumulating evidence suggests that interactions between the brain and gut microbiota significantly impact brain function and mental health. In the present study, we aimed to investigate whether young, healthy adults without psychiatric diagnoses exhibit differences in metabolic stool and microbiota profiles based on depression/anxiety scores and heart rate variability (HRV) parameters. Untargeted nuclear magnetic resonance-based metabolomics was used to identify fecal metabolic profiles. Results were subjected to multivariate analysis through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the metabolites were identified through VIP score. Metabolites separating asymptomatic and symptomatic groups were acetate, valine, and glutamate, followed by sugar regions, glutamine, acetone, valerate, and acetoacetate. The main metabolites identified in high vagal tone (HVT) and low vagal tone (LVT) groups were acetate, valerate, and glutamate, followed by propionate and butyrate. In addition to the metabolites identified by the PLS-DA test, significant differences in aspartate, sarcosine, malate, and methionine were observed between the groups. Levels of acetoacetate were higher in both symptomatic and LVT groups. Valerate levels were significantly increased in the symptomatic group, while isovalerate, propionate, glutamate, and acetone levels were significantly increased in the LVT group. Furthermore, distinct abundance between groups was only confirmed for the Firmicutes phylum. Differences between participants with high and low vagal tone suggest that certain metabolites are involved in communication between the vagus nerve and the brain. Keywords: amino acids; anxiety; depression; gut microbiota; gut–brain axis; metabolomics; short-chain fatty acids; vagal tone. PMID: 39195546 DOI: 10.3390/metabo14080450