Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

Fernanda Alvarenga Lima Barroso; Luís Cláudio Lima de Jesus; Tales Fernando da Silva; Viviane Lima Batista; Juliana Laguna; Nina Dias Coelho-Rocha; Kátia Duarte Vital; Simone Odília Antunes Fernandes; Valbert Nascimento Cardoso; Enio Ferreira; Flaviano Santos Martins; Mariana Martins Drumond; Pamela Mancha-Agresti; Alexander Birbrair; Debmalya Barh; Vasco Azevedo

doi:10.3389/fmicb.2022.858036

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

Front Microbiol. 2022 Apr 26:13:858036. doi: 10.3389/fmicb.2022.858036. eCollection 2022.

Authors

Fernanda Alvarenga Lima Barroso¹, Luís Cláudio Lima de Jesus¹, Tales Fernando da Silva¹, Viviane Lima Batista¹, Juliana Laguna¹, Nina Dias Coelho-Rocha¹, Kátia Duarte Vital², Simone Odília Antunes Fernandes², Valbert Nascimento Cardoso², Enio Ferreira³, Flaviano Santos Martins⁴, Mariana Martins Drumond^{1

5}, Pamela Mancha-Agresti¹, Alexander Birbrair³, Debmalya Barh^{1

6}, Vasco Azevedo¹

Affiliations

¹ Departamento de Genética, Ecologia e Evolução, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
² Departamento de Análises Clínicas e Toxicológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³ Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
⁴ Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
⁵ Departamento de Ciências Biológicas, Centro Federal de Educação Tecnológica de Minas Gerais, Belo Horizonte, Brazil.
⁶ Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, India.

Abstract

Intestinal mucositis promoted by the use of anticancer drugs is characterized by ulcerative inflammation of the intestinal mucosa, a debilitating side effect in cancer patients undergoing treatment. Probiotics are a potential therapeutic option to alleviate intestinal mucositis due to their effects on epithelial barrier integrity and anti-inflammatory modulation. This study investigated the health-promoting impact of Lactobacillus delbrueckii CIDCA 133 in modulating inflammatory and epithelial barrier markers to protect the intestinal mucosa from 5-fluorouracil-induced epithelial damage. L. delbrueckii CIDCA 133 consumption ameliorated small intestine shortening, inflammatory cell infiltration, intestinal permeability, villus atrophy, and goblet cell count, improving the intestinal mucosa architecture and its function in treated mice. Upregulation of Muc2, Cldn1, Hp, F11r, and Il10, and downregulation of markers involved in NF-κB signaling pathway activation (Tlr2, Tlr4, Nfkb1, Il6, and Il1b) were observed at the mRNA level. This work suggests a beneficial role of L. delbrueckii strain CIDCA 133 on intestinal damage induced by 5-FU chemotherapy through modulation of inflammatory pathways and improvement of epithelial barrier function.

Keywords: 5-FU-induced mucositis; Lactobacillus delbrueckii; anti-inflammatory cytokines; intestinal permeability; probiotics; tight junction proteins.