期刊
LIFE SCIENCES
卷 296, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.120445
关键词
Paraprobiotic; Enterococcus faecalis; EC-12; Irinotecan; Intestine; Mucositis
资金
- Finep-CT-INFRA
- CAPES-Pro-Equipamentos
- MCTI-CNPq-Sis-Nano2.0
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [421202/2018-1, 310568/2017-0]
- CAPES (Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior) [0756/2020 PROEX/CAPES, 23038.006689/2020-14]
- FUNCAP (Fundacao Cearense de Apoio ao Desenvolvimento Cientifico) [PR2-0101-00054.01.00/15]
This study demonstrated that purified paraprobiotic Enterococcus faecalis (EC-12) and an E. faecalis-based formulation (Med Lan-S) can protect against irinotecan-induced intestinal mucositis by downregulating the inflammatory response. EC-12 also prevented bacterial translocation to the blood induced by irinotecan.
Aims: This study tested the protective effect of purified paraprobiotic Enterococcus faecalis (EC-12) and an E. faecalis-based formulation (Med Lan-S) on irinotecan-induced intestinal mucositis murine model.Main methods: C57BL/6 male mice received saline, irinotecan (75 mg/Kg, i.p.), EC-12 (0.3, 1, or 3 x 10(7) CFU/Kg, p.o.) + irinotecan or Med Lan-S (3 x 10(7) CFU/Kg, p.o.) + irinotecan. Body mass variation was assessed daily, and blood samples were collected for evaluating bacteremia and leukocyte count. The ileum was harvested for myeloperoxidase assay, histopathology, quantitative PCR, and immunofluorescence for macrophages (F4/80), TLR4, and IL-18 binding protein (IL-18BP).Key findings: The best therapeutic strategy was EC-12 administration at 3 x 10(7) CFU/Kg, starting 1 week before irinotecan. EC-12 and Med Lan-S did not prevent the irinotecan-induced body mass loss or leukopenia but attenuated the neutrophil infiltration in the intestine and increased the villus/crypt ratio (P < 0.05). Additionally, EC-12 and Med Lan-S reduced the mRNA expression of Cldn-2, Ocln, and Tlr4 versus the irinotecan group (P < 0.05). Irinotecan also augmented the expression of Il-18, IL-18BP, the immunofluorescence of F4/80, and TLR4, while only EC-12 prevented the expression of all these markers. Remarkably, EC-12 and Med Lan inhibited the irinotecan-induced bacterial translocation to the blood.Significance: Paraprobiotic E. faecalis EC-12 prevents the development of intestinal mucositis by downregulating the inflammatory response. Med Lan-S also protects from mucositis. Possibly, the complexity of the formulation accounts for an innate immune-driven protective mechanism.
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