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Cecropin A Alleviates Inflammation Through Modulating the Gut Microbiota of C57BL/6 Mice With DSS-Induced IBD
Zhenya Zhai1, Fan Zhang1, Ruihua Cao1
1Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, Subtropical Institute of Animal Nutrition and Feed, South China Agricultural University, Guangzhou, China.
Abstract:
The present study is undertaken to assess the alleviating effects of antimicrobial peptide cecropin A on inflammatory bowel disease (IBD) in C57BL/6 mice and changes in the gut microbiota, compared to an antibiotic gentamicin. Different doses of cecropin A were intraperitoneally injected into C57BL/6 mice for 5 days to determine the safe doses. The injection doses at ≤ 15 mg/kg showed no negative impact on the liver, heart, spleen, and kidney. The severe and moderate IBD mice model was successfully established via supplementation of 4 or 2.5% dextran sulfate sodium (DSS) in drinking water for 5 days. The severe IBD model was used to ensure the optimal therapeutic dose of cecropin A. Survival rate, body weight and disease activity index (DAI) scores were measured. Administration of 15 mg/kg, not 5 mg/kg cecropin A, for 5 days increased survival rate and decreased body weight loss of mice. The moderate IBD model was applied to investigate the mechanisms for cecropin A to alleviate inflammation in comparison to gentamicin. The mice were treated with 15 mg/kg cecropin A or 5 mg/kg gentamicin for 3 days. The levels of cytokines and related proteins in the colon were detected by ELISA and Western blotting. The microbiota in cecum contents were analyzed using 16S rRNA gene sequencing. The results showed that cecropin A and gentamicin relieved body weight loss, DAI, and gut mucosa disruption, while decreasing tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), and interlukin-6 (IL-6) induced by DSS. In addition, cecropin A and gentamicin showed different effects on the gut microbiota structure. Both cecropin A and gentamicin decreased DSS-induced enrichment of Bacteroidaceae and Enterobacteriaceae. However, cecropin A showed a selective enrichment of Lactobacillus in contrast to gentamicin, which demonstrated a selective effect on Desulfovibrionaceae and Ruminococcaceae. Cecropin A alleviates IBD through decreasing harmful gut microflora and specifically enhancing beneficial gut microflora. The mechanism of this effect is different from gentamicin.
Insights
Antimicrobial peptide cecropin A effectively alleviates inflammatory bowel disease (IBD) in mice by reducing harmful gut bacteria and promoting beneficial ones like Lactobacillus. Its therapeutic mechanism differs from the antibiotic gentamicin.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Inflammatory bowel disease (IBD) is a chronic condition characterized by gut inflammation.
- Gut microbiota dysbiosis is implicated in IBD pathogenesis.
- Antimicrobial peptides (AMPs) like cecropin A are being investigated for therapeutic potential.
Purpose of the Study:
- To evaluate the therapeutic effects of cecropin A on dextran sulfate sodium (DSS)-induced IBD in C57BL/6 mice.
- To compare the efficacy and gut microbiota modulation of cecropin A with the antibiotic gentamicin.
- To elucidate the underlying mechanisms of cecropin A in alleviating IBD.
Main Methods:
- Establishment of severe and moderate IBD mouse models using DSS.
- Intraperitoneal administration of varying cecropin A doses to determine safety and efficacy.
- Assessment of survival rates, body weight, disease activity index (DAI), and colonic cytokine levels (TNF-α, IL-1β, IL-6).
- Analysis of gut microbiota composition using 16S rRNA gene sequencing.
Main Results:
- Cecropin A (15 mg/kg) significantly improved survival rates and reduced body weight loss in severe IBD mice.
- Both cecropin A and gentamicin reduced DAI, gut mucosal damage, and key inflammatory cytokines (TNF-α, IL-1β, IL-6).
- Cecropin A selectively enriched beneficial *Lactobacillus* species, while gentamicin affected *Desulfovibrionaceae* and *Ruminococcaceae*.
- Both treatments decreased the abundance of detrimental *Bacteroidaceae* and *Enterobacteriaceae*.
Conclusions:
- Cecropin A demonstrates significant therapeutic potential for IBD by mitigating inflammation and restoring gut microbiota balance.
- Cecropin A's mechanism involves reducing pathogenic bacteria and promoting beneficial bacteria, distinct from gentamicin's effects.
- Cecropin A represents a promising alternative therapeutic agent for IBD management.
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