Therapeutic potential of Bacillus-derived lipopeptides in controlling enteropathogens and modulating immune responses to mitigate post-weaning diarrhea in swine

Abstract

Post-weaning diarrhea (PWD) is a major concern for pig producers, as stress and early weaning increase susceptibil-ity to enteropathogens like enterotoxigenic Escherichia coli (ETEC) and Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). This study explores the immunomodulatory and antimicrobial properties of lipopeptide extracts (LPEs) from Bacillus strains which contain surfactin (SF) - an immunomodulatory lipopeptide - and their potential in mitigating PWD. Pre-incubation with LPEs from B. subtilis TC12, containing 1, 40 and 60 µg/ml SF, stimulated TNF-α production significantly (p < 0.05) in LPS-challenged RAW 264.7 cells. In contrast, B. velezensis MFF 2.2 LPE, containing 0.1 and 1 µg/ml SF, reduced TNF-α production by macrophages after LPS-challenge. The production of IFN-γ by these cells was not affected by pre-incubation with any of the extracts. On the other hand, all treatments significantly decreased (p < 0.05) IL-10 production. LPEs significantly reduced (p < 0.05) NO production; however, neither TC12 nor MFF 2.2 LPEs affected macrophage phagocytic activity or bactericidal capacity and, in addition, LPEs showed bacteriostatic activ-ity towards S. Typhimurium and ETEC. Also, LPEs did not affect RAW 264.7 viability (> 90%) in concentrations up to 60 µg/ml SF for TC 12 and 1 µg/ml for MFF 2.2. These findings suggest that LPEs from native Bacillus possess immu-nomodulatory and antimicrobial properties, which could help control inflammation and inhibit pathogen growth during piglet weaning. According to preliminary in vivo studies, LPEs might offer a promising alternative to reduce antibiotic usage in pig husbandry.