Resistant Starch‐Capric Acid Effectively Improves Lipopolysaccharide‐Induced Depressive Behavior by Protecting the Intestinal Microbiota Barrier and Inhibiting Inflammatory Responses

Previous studies have found that gut flora, immunity, and neuroinflammation play key roles in the pathogenesis of depression, and fatty acids are neuroprotective. The present study aimed to reveal the effects of capric acid intake (absorbed in the colon via resistant starch complex) on LPS-induced depression-like behavior and its underlying mechanisms. Male ICR mice were ingested with resistant starch-decanoic acid complex (RS-FA, 13 g/kg) for 50 consecutive days. The depression model was established by injecting LPS (0.5 mg/kg every two days for three injections). The results of behavioral tests showed that the mice pretreated with resistant starch capric acid complex had significantly shorter resting time in the tail suspension test (TST); the number of crossing grids and the number of standing in the open field test (OFT) were significantly increased. In addition, TNF-α levels in the serum of depressed mice were decreased; 5-HT levels in the hippocampus were increased. It had an ameliorative effect on the haphazard arrangement of colonic glandular cells caused by LPS, as well as nuclear condensation and eosinophilic degeneration of hippocampal neurons. 16S rRNA analysis revealed that pretreatment with resistant starch-capric acid complexes reversed depression-associated dysbiosis, restoring gut microbial composition to levels approaching those of the control group. Restores uniformity in the animal gut microbiota, increases beneficial bacterial populations, and demonstrates efficacy in elevating short-chain fatty acid levels. Furthermore, resistant starch-capric acid concurrently modulates the TLR4/NF-κB signaling pathway and the tryptophan metabolic pathway to regulate gut microbiota dysbiosis in depressed mice.