Probiotic intervention, already showing promise in the treatment of various psychiatric disorders like depression, emerges as a potential therapy for anorexia nervosa (AN) with minimal side effects. In this study, we established an activity-based anorexia (ABA) model to probe the pathogenesis of AN and assess the impact of probiotics on ABA mice. ABA resulted in a compensatory increase in duodenal ghrelin levels, impairing the regulation of feeding and the brain reward system. Intervention with Streptococcus salivarius subsp. thermophilus CCFM1312 ameliorated these ABA-induced effects, and the activation of neurons in the nucleus tractus solitarius (NTS) was observed following probiotic administration, revealing the advantageous role of probiotics in AN through the vagus nerve. Furthermore, our metabolomics analysis of cecal contents unveiled that S. salivarius subsp. thermophilus CCFM1312 modulated gut microbiota metabolism and thereby regulated intestinal ghrelin levels.