Vespa orientalis Pupae Peptide Hydrolysates Modulate NF-κB Signaling in LTA-Induced Pneumonia from Clinical Enterococcus faecalis Isolates: Implications for Gut Microbiota

Mujeeb Ur Rahman^1*Muhammad Ilyas¹AAMNA ATTA¹Yamina Alioui¹Sharafat Ali¹Hidayat Ullah²Muhsin Ali¹Ting Deng¹Nabeel Ahmed Farooqui¹Renzhen Ma¹Mohammed Abusidu¹Jiayi Wang³Liang Wang³Yi Xin^1*

• ¹Dalian Medical University, Dalian, China
• ²Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, PR China., Dalian Medical University, Dalian, China
• ³Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China, Dalian Medical University, Dalian, China

Pneumonia remains a prevalent primary infectious disease characterized by persistent lung inflammation, resulting in respiratory distress and significant mortality rates, particularly among young children in low-income countries. This study investigated the therapeutic potential of peptide hydrolysates derived from Vespa orientalis pupae in a murine model of clinically isolated Enterococcus faecalis lipoteichoic acid (LTA)-induced pneumonia, which represents bacteria-triggered pulmonary inflammation. Administration of pupae peptide hydrolysate (PPH) effectively mitigated LTA-induced symptoms, including weight gain, reduced pulmonary and colonic inflammation, and rectified gut microbiome imbalances. PPH notably enhanced intestinal integrity by increasing the expression of mucin-2, mucin-4, and tight junction proteins (Claudin-1, Occludin, ZO-1). Treatment also modulated the immune response by decreasing pro-inflammatory cytokines while elevating anti-inflammatory cytokine levels, an effect associated with the downregulation of NF-κB signaling in the lungs. Furthermore, PPH facilitated substantial restoration of the gut microbiota composition, as evidenced by 16S rRNA sequencing results, indicating potential gut flora-enhancing effects. These findings highlight the therapeutic efficacy of PPH against LTA-induced pneumonia by enhancing the intestinal barrier, modulating inflammatory responses, including NF-κB pathway suppression, and restoring intestinal homeostasis, presenting a novel approach for addressing pneumonia as a chronic inflammatory condition.