The probiotic strain Bacillus subtilis CU1 primes antimicrobial innate immune response and reduces low-grade inflammation: a clinical study.

Abstract

LifeinU™ Bacillus subtilis CU1 (BSCU1) has been previously shown to be effective in stimulating mucosal immune responses and supporting resistance to common infectious disease episodes in the elderly. The current clinical study aimed at exploring potential pathways by which BSCU1 could beneficially modulate the immune system and contribute to protection against infection in the general population. A total of 88 participants from three different age groups were supplemented with BSCU1 (2 × 109 cfu/day) for 4 weeks. The effect of the intervention on mucosal immunity was assessed by faecal sIgA levels. In addition, a series of complementary immunoassays were selected, including immune phenotyping, gene expression, basal cytokine levels, cytokine levels in lipopolysaccharide (LPS)-stimulated whole blood and phagocytosis assay. Although no significant effect was observed on faecal sIgA levels after intervention, BSCU1 showed a positive effect on a consistent set of markers of the peripheral innate immune system in adults and the elderly. Percentages of peripheral blood myeloid cells as well as the expression of the activation marker CD69 on monocytes were significantly increased after probiotic intervention. BSCU1 supplementation resulted in significant enrichment of clusters of genes involved in response to type I interferon and phagocytosis pathway. Consistently, ex vivo stimulation of whole blood with LPS resulted in a statistically significant increase in pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6, interferon-gamma, IL-12, tumour necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, IL-8) and phagocytosis assays showed increased capacity of monocytes to engulf bacteria as well as higher phagosome maturation. BSCU1 supplementation also had a positive effect on low-grade inflammation as significant reduction in basal levels of several serum cytokines (IL-10, TNF-alpha, MIP-1alpha, IL-8) were observed in the elderly subgroup. Overall, BSCU1 primed immune cells for a better response to microbial challenges and reduced low-grade inflammation associated with aging. Registered at ClinicalTrials.gov with the identifier NCT05403398.