Comparative preventive effects of probiotic and postbiotic preparations of Lacticaseibacillus rhamnosus L156.4 and GG in a 5-FU-induced mucositis model

Intestinal mucositis is a debilitating side effect of chemotherapy, characterized by epithelial damage, inflammation, and microbial dysbiosis, that significantly impairs patients' quality of life. This study evaluated the therapeutic potential of Lacticaseibacillus rhamnosus L156.4 in its live, heat-inactivated, and supernatant forms, compared to the reference strain L. rhamnosus GG (LGG), in a murine model of 5-fluorouracil (5-FU)-induced mucositis. Preventive treatment with live L156.4 significantly reduced mucositis-induced intestinal damage, preserving villus length, crypt depth, and goblet cell numbers, thereby supporting barrier integrity. In contrast, heat-inactivated and supernatant forms provided only limited protection. Both live L156.4 and LGG reduced myeloperoxidase activity and downregulated inflammatory markers such as Il1b and Nfkb1, confirming anti-inflammatory effects. They also modulated tight junction-related gene expression with L156.4 showing strong induction of Muc2, suggesting enhanced epithelial protection. Fecal microbiota analysis showed that, whereas LGG restored the loss of bacterial diversity and evenness induced by 5-FU, L156.4 primarily modulated microbiota composition by restoring the abundance of specific phyla and genera. Overall, our findings identify L156.4 as a promising probiotic candidate, with effects comparable to and complementarity with LGG, for mitigating chemotherapy-induced mucositis. Further studies are required to assess dose effects and long-term safety.