The Influence of Omega‐3 Fatty Acids and Probiotics on Hippocampal Inflammation and Glial Cells in a Chronic Anorexia Nervosa Rat Model

Objective: Anorexia nervosa (AN) is a severe eating disorder associated with brain volume reduction, glial cell loss, microbiome alterations, and dysregulated pro-inflammatory mechanisms. However, the underlying cellular mechanisms remain inadequately elucidated, and interventions addressing these alterations are lacking. Method: This study employed a chronic activity-based anorexia (ABA) rat model to investigate hippocampal glial and neuronal cell alterations, inflammation, and microbial modifications in the gut. Omega-3 fatty acids and a multi-strain probiotic were examined as potentially protective agents. Cell count, proliferation, and apoptosis rates of microglia, neurons, astrocytes, and oligodendrocytes were analyzed in the hippocampus. Furthermore, local gene expression of pro-inflammatory cytokines and microRNA was measured. The hippocampal volume was determined longitudinally using 7-Tesla MRI scans before and after starvation. Finally, the fecal microbiome was analyzed to identify potential associations with brain and clinical characteristics. Results: Results confirmed the previously described reduction in astrocytes and newly demonstrated a decrease in oligodendrocytes in the hippocampus. Increased levels of IBA1-positive cells and pro-inflammatory cytokines suggest microglial activation in this region. Administering omega-3 and probiotics to starved animals reduced neuroinflammation and microglial activation in the hippocampus, resulting in significantly increased neuronal cell counts in the omega-3 group. Microbiome composition was primarily affected by the ABA model, and to a lesser extent by omega-3 and probiotics.