Hericium erinaceus peptide KSPLY protects gastric mucosal barrier and reshapes gastric microbiota in mice

Hericium erinaceus is rich in bioactive components and has long been studied for its improvement in gastric diseases. This study aimed to investigate the effects of a bioactive peptide KSPLY derived from H. erinaceus on Helicobacter pylori -caused gastric barrier injury and gastric microbiota changes. Results indicated that KSPLY significantly inhibited the expression of inflammatory factors and the activation of NF-kB signaling pathways in H. pylori -infected mice. Besides, KSPLY increased the gastric expressions of tight junctions and the pepsinogen I/l ratio. Furthermore, 16S rRNA sequencing analysis showed that KSPLY recovered the decrease in gastric microbiota diversity and structural imbalance caused by H. pylori infection. The relative abundance of beneficial bacteria such as Muribaculaceae , Alcaligenaceae , and Bifdobacteriaceae was increased, which were significantly negatively correlated with the changes in inflammatory factors. This study will offer a new direction for the application of H. erinaceus in the treatment of gastric diseases. This graphic abstract indicates the effects of an immunological peptide derived from H. erinaceus KSPLY on H. pylori-caused gastric barrier injury as well as the gastric microbiota changes. • A non-antibiotic strategy alleviated H. pylori -induced gastropathy. • KSPLY inhibited the NF-kB pathway and pro-inflammatory cytokines in infected mice. • KSPLY resorted mucosal integrity and functional recovery. • KSPLY reversed H. pylori -induced dysbiosis and increased beneficial bacteria.