Human cathelicidin LL-37 exerts amelioration effects against EHEC O157:H7 infection regarding inflammation, enteric dysbacteriosis, and impairment of gut barrier function.
Fang. Xin X; Nong. Keyi K; Wang. Zihan Z; Jin. Yuanli Y; Gao. Feng F; Zeng. Qiuyu Q; Wang. Xuemei X; Zhang. Haiwen H
Key Findings
- LL‑37 prevented weight loss and repaired damage to intestinal villi in infected mice.
- It lowered pro‑inflammatory cytokines (IL‑1β, IL‑6, TNF‑α) and raised anti‑inflammatory IL‑10.
- Tight‑junction proteins (ZO‑1, ZO‑2, claudin‑1, occludin) were increased, strengthening gut barrier function.
- Gut microbiota dysbiosis caused by EHEC was partially corrected, and bacterial load in liver and spleen dropped.
Practical Outcomes
- For DIY health enthusiasts, the study suggests that boosting LL‑37 levels might help protect gut integrity and reduce inflammation during bacterial infections, but the work is limited to mice and uses direct peptide administration not yet proven safe or practical in humans. Until human trials or safe delivery methods are available, LL‑37 remains more of a research insight than a ready‑to‑use supplement.
Summary
In mice infected with a harmful E. coli strain, giving the natural peptide LL‑37 helped keep weight stable, protected gut lining, lowered inflammation, and improved the balance of gut bacteria. It also reduced the spread of bacteria to the liver and kidneys, suggesting LL‑37 can boost gut health during infection.
Abstract
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection impairs intestinal barrier function, causing intestinal inflammation and enteric dysbacteriosis. The human cathelicidin LL-37 can regulate excessive inflammatory responses, barrier function, and balance the intestinal microbial community; however, little is known about its effects on inflammation, intestinal barrier function, and microbiota disorders in EHEC O157:H7-infected mice. In this study, we investigated the protective effect of LL-37 against EHEC O157:H7 infection and elucidated the underlying mechanism using a mouse model. LL-37 treatment was found to inhibit body weight loss, restore edema and destruction of the intestinal villi, and significantly reduce epithelial apoptosis (P < 0.05) in EHEC O157:H7-infected mice. Furthermore, inflammatory infiltration of macrophages and neutrophils into the jejunum and colon was significantly decreased (P < 0.05). LL-37 significantly downregulated the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) (P < 0.05) and upregulated the anti-inflammatory cytokine (IL-10) during EHEC O157:H7 infection. LL-37 increased the expression of tight junction proteins (ZO-1, ZO-2, claudin-1, and occludin), which are associated with intestinal barrier function, and had a positive effect on EHEC O157:H7-induced microbial disorders, particularly in terms of the inflammation-related microbiota. LL-37 also significantly decreased the E. coli load in the liver and spleen (P < 0.01) and restored the structure of the liver and kidney. Taken together, LL-37 conferred protection in a EHEC O157:H7-induced mouse model by reducing intestinal inflammation, enhancing intestinal barrier function, and restoring the balance of the intestinal microbiota, which indicates the therapeutic potential of LL-37 against pathogen infection.
Study Information
pubmed
2022
2022-11-09T00:00:00.000Z
10.1016/j.peptides.2022.170903
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