Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation

Abstract

Intestinal mucositis is a commonly reported side effect in oncology practice. Probiotics are considered an excellent alternative therapeutic approach to this debilitating condition; however, there are safety questions regarding the viable consumption of probiotics in clinical practice due to the risks of systemic infections, especially in immune-compromised patients. The use of heat-killed or cell-free supernatants derived from probiotic strains has been evaluated to minimize these adverse effects. Thus, this work evaluated the anti-inflammatory properties of paraprobiotics (heat-killed) and postbiotics (cell-free supernatant) of the probiotic <i>Lactobacillus delbrueckii</i> CIDCA 133 strain in a mouse model of 5-Fluorouracil drug-induced mucositis. Administration of paraprobiotics and postbiotics reduced the neutrophil cells infiltrating into the small intestinal mucosa and ameliorated the intestinal epithelium architecture damaged by 5-FU. These ameliorative effects were associated with a downregulation of inflammatory markers (<i>Tlr2</i>, <i>Nfkb1</i>, <i>Il12</i>, <i>Il17a</i>, <i>Il1b</i>, <i>Tnf</i>), and upregulation of immunoregulatory <i>Il10</i> cytokine and the epithelial barrier markers <i>Ocln</i>, <i>Cldn1</i>, <i>2</i>, <i>5</i>, <i>Hp</i> and <i>Muc2</i>. Thus, heat-killed <i>L. delbrueckii</i> CIDCA 133 and supernatants derived from this strain were shown to be effective in reducing 5-FU-induced inflammatory damage, demonstrating them to be an alternative approach to the problems arising from the use of live beneficial microorganisms in clinical practice.