Chronic stress (CS) endangers the physical and mental health of adolescents. Therefore, alleviating and preventing such negative health impacts are a top priority. This study explores the effect of feeding shrimp head hydrolysate (SHH) on gut microbiota, short-chain fatty acids (SCFAs), and neurotransmitters in growing C57BL/6 mice subjected to chronic unpredictable mild stress. Mice in the model group and three SHH groups were exposed to CS for 44 days, distilled water and SHH doses of 0.18, 0.45, 0.90 g/kg·BW were given respectively by gavage daily for 30 days from the 15th day. The results showed that SHH can significantly reverse depression-like behaviour, amino acids degradation, α diversity and β diversity, proportion of Firmicutes and Bacteroidota, abundance of genera such as Muribaculaceae, Bacteroides, Prevotellaceae_UCG-001, Parabacteroides and Alistipes, concentration of five short-chain fatty acids (SCFAs), 5-HT and glutamate induced by CS. Muribaculaceae and butyric acid may be a controlled target. This study highlights the potential and broad application of SHH as an active ingredient in food to combat chronic stress damage.

Lutjanus erythropterus protein (Lep) exhibits anti-inflammatory effects, but its antidepressant activity is unknown. This study used a 44-day chronic unpredictable mild stress (CUMS) model to determine whether Lep has a beneficial effect through the gut–brain axis in 3-week-old male C57BL/6 mice. Gavaging with Lep solution alleviated the depression-like behavior and anxiety symptoms in CUMS growing mice. Administration of Lep decreased serum IL-1β, IL-2, IL-6, and TNF-α levels and restored colonic mucosal damage. In addition, Lep improved the disturbance of 5-hydroxytryptamine (5-HT) secretion in the gut–brain axis. Pearson analysis revealed that gut short-chain fatty acid (SCFAs) concentration significantly (p < 0.05) correlated with mucosal damage scores and the depression-like behavior index. Lep was able to prevent the gut SCFA enrichment. Lep upregulated gut Muribaculaceae and downregulated SCFA-producing bacteria by replenishing deficient amino acid (AA) (tryptophan, alanine, aspartate, glutamate) and decreased (p < 0.01) the gene abundance of the AA metabolism pathway of SCFA-producing bacteria, thereby preventing gut SCFA enrichment and alleviating associated depression-like behavior. These findings indicate that Lep could attenuate depression in CUMS juvenile mice via the gut microbiota-SCFA–brain axis.