AUTHOR=Barbosa Stphannie Jamyla de Araújo , Oliveira Maisie Mitchele Barbosa , Ribeiro Susana Barbosa , de Medeiros Caroline Addison Carvalho Xavier , Lima Maria Laura de Souza , Guerra Gerlane Coelho Bernardo , de Araújo Júnior Raimundo Fernandes , de Sousa Junior Francisco Caninde , Martins Agnes Andrade , Paiva Daniel Felipe Fernandes , Andrade Raphael Victor Silva , Rebouças Conceição S. Martins , Brito Gerly Anne de Castro , Leitâo Renata Ferreira de Carvalho , de Araújo Aurigena Antunes 

TITLE=The beneficial effects of Lacticaseibacillus casei on the small intestine and colon of Swiss mice against the deleterious effects of 5-fluorouracil

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.954885

DOI=10.3389/fimmu.2022.954885

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Intestinal mucositis is one of the most common and important side effects of 5-fluorouracil (5-FU). Currently, there are still no specific and effective protocols for its prevention and treatment. The aim of the present study was to evaluate the effect of oral administration of Lacticaseibacillus casei (<italic>L. casei</italic>) on the progression of 5-FU-induced intestinal mucositis. Methods: <italic>L. casei</italic> (1x10<sup>9</sup> CFU/ml) or saline was orally administered to Swiss mice, beginning 15 days before intestinal mucositis induction by single intraperitoneal 5-FU administration (450 mg/kg). Body weight, number of peripheral leukocytes and fecal lactic acid bacteria were monitored. After euthanasia, on day 18, tissue samples from colon and each small intestine segment were collected for histopathology. Jejunal tissues were collected and evaluated for iNOS and TNF-alpha immunoexpression, IL-1-beta, IL-6 and TNF-alpha levels, malonaldehyde (MDA) accumulation, invertase activity and factor nuclear kappa B (NFkB-P65) gene expression, toll like receptor-4 (TLR-4), mucin-2 (MUC-2), occludin and zonula occludens-1 (ZO-1).</p></sec><sec><title>Results</title><p>The positive impact of <italic>L. casei</italic> on 5-FU-induced leukopenia was observed, but not on 5-FU-induced weight loss in mice. <italic>L. casei</italic> reduced 5-FU-induced inflammation in the colon and small intestine (p&lt;0.05). Decreased TNF-α, IL-1β, IL-6 (p&lt;0.05) and MDA (p&lt;0.05) levels, as well as decreased iNOS and TNF-alpha protein expressions (p&lt;0.05) were found in the jejunum from <italic>L casei</italic> group. In addition, <italic>L-casei</italic> down-regulated NFKB-P65 (p&lt;0.05) and TLR-4 (p&lt;0.05) gene expressions and up-regulated MUC-2 and mucosal barrier proteins occludin and ZO-1 gene expressions (p&lt;0.05). Furthermore, greater lactic acid bacteria population (p&lt;0.05) was found in the <italic>L. casei</italic> group when compared to control groups.</p></sec><sec><title>Conclusion</title><p>Oral <italic>L. casei</italic> administration can protect the intestine of Swiss mice from 5-FU-induced intestinal mucositis, thus contributing to overall health.</p></sec>