Bifidobacterium Longum as an Orally Administered Carrier of LL-37 to Treat Bacterial Diarrhea

Qing Guo; Shiyu Li; Yajie Xie; Zhenrui Xu; Mengge Liu; Qian Zhang; Hanxiao Sun

Bifidobacterium Longum as an Orally Administered Carrier of LL-37 to Treat Bacterial Diarrhea

Qing Guo, Shiyu Li, Yajie Xie, Zhenrui Xu, Mengge Liu, Qian Zhang, Hanxiao Sun

Abstract

LL-37 is the only antibacterial peptide of the cathelicidin family found in the human body. It has antimicrobial activity and is able to neutralize endotoxins, with no obvious toxic effects on probiotics. In the present study, we engineered Bifidobacterium longum (B. longum) as an experimentally constructed delivery system of LL-37 to treat bacterial diarrhea. The results showed that the engineered B. longum successfully secreted LL-37, at a level of 57 ± 6.8 ?g/ml after fermentation for 42 h. The supernatant containing recombinant LL-37 significantly inhibited the growth of Escherichia coli (E. coli ) and Staphylococcus aureus (S. aureus), and markedly decreased TNF-? levels in LPS-induced RAW264.7 cells. This modified B. longum was orally administered after bacterial diarrhea was induced with E. coli, and resulted in significant reduction of the proinflammatory cytokine TNF-?. The anti-inflammatory cytokine IL-10 and mucosal repair factor TGF-? were remarkably increased, and the intestinal bacteria Lactobacillus and Bifidobacterium, as well as E. coli, were well-regulated. Histological observations showed colonic protection with dose-modified B. longum. The results demonstrated effective resistance to bacterial diarrhea with LL-37–secreting B. longum.

Keywords

Bifidobacterium longum, LL-37, bacterial diarrhea, endotoxin, antibacterial activity, oral administration

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