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ABSTRACT Surfactin, a lipopeptide biosurfactant produced by Bacillus spp., has emerged as a promising bioactive compound due to its potent inhibitory effects on bacterial and viral pathogens. This showcases its potential as a non-antibiotic strategy for managing infectious diseases. Our investigation reveals that surfactin administration significantly promotes weight gain and improves immune organ indices in mice, reflecting enhanced immunity and gut health. Surfactin augments phagocytic function in peritoneal macrophages and boosts proliferative responses in splenic lymphocytes post-chicken red blood cell immunization. Furthermore, it increases intestinal villi height, indicative of superior nutrient absorption. It elevates mucin secretion and expression of intestinal mucosal proteins, such as secretory IgA, Muc1, and Muc2, and tight junction proteins claudin-1, occludin, and Zo-1 in the jejunum and colon. Crucially, surfactin modifies the gut microbiota composition by reducing Escherichia coli populations and ameliorating cyclophosphamide-induced gut dysbiosis. Our data suggest that oral surfactin could be a valuable therapeutic modality to alleviate immune suppression and gut damage, proposing a new pathway for immunomodulatory treatment.IMPORTANCEThe potential of surfactin as a microbial surfactant extends beyond its surfactant properties, impacting immune regulation and gut health. As the need for alternatives to traditional antibiotics continues to grow, surfactin’s ability to enhance host defense mechanisms against common pathogens without directly targeting them with antibiotics offers a strategic advantage. Understanding how surfactin shapes the immune landscape and the gut microbiome can inform innovative interventions against immunosuppression and intestinal impairment, particularly in contexts such as cyclophosphamide-induced toxicity.

Activation of small intestinal gluten-reactive CD4+ T cells is a critical event in celiac disease. Such cells predominantly recognise gluten peptides in which specific glutamines are deamidated. Deamidation may be catalysed by intestinal tissue transglutaminase (TG2), a protein which is also the main autoantigen in celiac disease. Our aim was to study how the two main catalytic activities of transglutaminase—deamidation and transamidation (cross-linking) of an immunodominant gliadin epitope—are influenced by the presence of acceptor amines in the intestinal mucosa, and thereby contribute to further elucidation of the pathogenetic mechanisms in celiac disease. We prepared monoclonal antibodies, reacting specifically with the non-deamidated epitope QPFPQPQLPYPQPQ-amide and/or the deamidated epitope QPFPQPELPYPQPQ-amide. A solid phase immunoassay combined with gel filtration chromatography was used to analyse deamidation and cross-linking of these peptides to proteins. Our results show that QPFPQPQLPYPQPQ-amide was deamidated when incubated with purified TG2, with fresh mucosal sheets and with mucosal homogenates. Of other transglutaminases tested, only Streptoverticillium transglutaminase was able to generate the deamidated epitope. A fraction of the non-deamidated epitope was cross-linked to proteins, including TG2. The results suggest that intestinal TG2 is responsible for generation of the active deamidated epitope. As the epitope often occurs in a repeat structure, the result may be cross-linking of a deamidated, i.e., activated cell epitope. Alternatively, the deamidation may occur by reversal of the cross-linking reaction. The results provide a basis for the suggestion that binding of a peptide to a protein, in connection to its modification to a T cell epitope, might be a general explanation for the role of TG2 in celiac disease and a possible mechanism for the generation of autoantigens. [Copyright &y& Elsevier]