Acute consumption of a multi-source peptide complex is associated with coordinated innate immune and hematopoietic stem cell responses: An exploratory pilot study

Background: Immune surveillance and regenerative responses depend on coordinated interactions among innate immune cells and hematopoietic progenitor populations. Food-derived peptides have been reported to influence immune function, but little is known about their acute effects across multiple interconnected immune and stem cell compartments. Objectives: This exploratory pilot study evaluated whether acute consumption of a multi-source peptide complex (MSPC) was associated with coordinated changes in circulating immune and stem cell populations. Methods: In a randomized, placebo-controlled pilot study, four healthy adults (N=4) consumed MSPC or placebo, and peripheral blood was collected before and after consumption. Flow cytometric analyses were performed to evaluate monocyte numbers and phenotype, γδ T cells, natural killer (NK) cells, and circulating stem/progenitor cell populations, including CD45dimCD34+ hematopoietic stem/progenitor cells and CD45-CD31++CD34- endothelial progenitor cells. Results: MSPC consumption was associated with rapid and temporally organized changes across multiple cellular compartments. Within the monocyte compartment, coordinated increases in CD14 and CD16 expression occurred despite stable monocyte numbers, suggesting phenotypic remodeling rather than redistribution among classical, intermediate, and non-classical monocytes. Intermediate monocytes also demonstrated increased expression of the co-stimulatory molecules CD80 and CD86. In parallel, γδ T cell numbers decreased while expression of the activation-associated markers CD25 and CD69 increased, consistent with altered trafficking behavior and activation status. Circulating NK cell numbers increased, but the change did not reach statistical significance compared to placebo. In addition, MSPC consumption was associated with selective mobilization of circulating CD45dimCD34+ hematopoietic stem/progenitor cells, whereas CD45-CD31++CD34- endothelial progenitor cell numbers were unchanged relative to placebo. Conclusions: In this small and exploratory pilot study, acute MSPC consumption was associated with selective and temporally coordinated changes spanning immune and hematopoietic compartments rather than broad immune activation. The convergence of monocyte remodeling, γδ T-cell activation-associated changes, and hematopoietic stem/progenitor cell mobilization is consistent with the possibility that MSPC may influence interconnected immune and hematopoietic communication pathways involved in immune surveillance and hematopoietic regulation. Given the exploratory design and small sample size, these observations should be considered hypothesis-generating, with their reproducibility, functional significance, and durability to be evaluated in larger studies. Novelty of the Study: This proof-of-concept clinical trial provides novel evidence that acute consumption of a complex blend of peptides was associated with coordinated changes across both innate immune and stem/progenitor cell populations. Whereas previous publications have largely focused on individual stem cell or natural killer cell populations, this exploratory study evaluated multiple stem cell and innate immune cell types, allowing assessment of their relative timing and patterns of response. Rather than occurring as isolated cellular events, the observed changes converged within a common post-consumption window, consistent with the possibility of shared regulatory signals acting across multiple cellular compartments. Keywords: Bioactive peptides; Cell mobilization; Immune surveillance; Innate immunity; Monocytes; γδ T cells; Hematopoietic stem and progenitor cells; Immune-hematopoietic communication.