Bacillus subtilis-Derived Surfactin Alleviates Offspring Intestinal Inflammatory Injuries Through Breast Milk

Enteric and diarrheal diseases pose a significant threat to infant health, highlighting the importance of immune defenses in early life, especially maternal protection, in establishing a robust gastrointestinal environment. Surfactin, a bioactive peptide from Bacillus subtilis, has immunomodulatory properties, yet its influence on offspring via maternal gut interference is not fully understood. This study examines the effects of maternal surfactin consumption on breast milk's immunological properties and its consequent effects on neonatal intestinal health.

Twenty-eight gravid mice were randomly categorized into two cohorts and were given surfactin or not in drinking water from one week after conception to 21 days postpartum. Cross-fostering experiments were conducted within 12 h after birth. Pups from the surfactin-supplemented dams were fostered and nursed by the control dams, while the pups from the control dams were nursed by the surfactin-supplemented dams.

The findings show that the pups from the surfactin-supplemented dams had increased body weight, improved intestinal morphology with longer villus and deeper crypts, the upregulation of genes related to mucins and antimicrobial peptides, and an increase in IgA⁺ and CD3⁺ T cells within the intestinal mucosa. Further, the cross-fostering experiments suggested that the pups nursed by the surfactin-supplemented dams gained more weight, had less intestinal damage, less inflammation, and lower oxidative stress levels induced by Salmonella typhimurium, indicating the immunological benefits of surfactin conveyed through breast milk. Additionally, the expression of pro-inflammatory factors, including nitric oxide, TNF-α, IL-1β, IL-6, MCP-1, and ROS, induced by LPS in the macrophages was significantly inhibited with milk from the surfactin-supplemented dam (MSD) treatment. Interestingly, the MSD treatment induced a shift in macrophage polarization from pro-inflammatory (M1-like) to anti-inflammatory (M2-like), evidenced by the decreased expression of IL-12p40 and iNOS and the increased expression of CD206, TGF-β, and Arg-1. In terms of mechanism, surfactin improved the contents of the anti-inflammatory factors IL-4, IL-10, and TGF-β in the breast milk.

This research contributes to understanding how maternal interference can modulate breast milk composition, influence infant gastrointestinal development and immunity, and provide nutritional strategy insights.