Clearance of multiple antibiotic-resistant coagulase-negative staphylococci is selectively associated with higher circulating α-melanocyte stimulating hormone in patients evaluated for chronic inflammatory response syndrome

Introduction: Neuroimmune regulatory peptides play central roles in coordinating inflammatory, metabolic, and mucosal immune processes in humans. Among these, α-melanocyte stimulating hormone (α-MSH), a proopiomelanocortin-derived peptide, has been implicated in modulation of cytokine signaling, epithelial barrier function, and pain processing. However, determinants of circulating α-MSH levels in chronic inflammatory states remain incompletely characterized in human clinical populations. Persistent sinonasal colonization with multiple antibiotic-resistant coagulase-negative staphylococci (MARCoNS) has been reported in some cohorts presenting with environmentally associated multisystem illness, described in some clinical settings as Chronic Inflammatory Response Syndrome (CIRS). Yet its relationship to systemic neuroendocrine biomarkers has not been quantitatively examined. Methods: This retrospective observational cohort study examined whether follow-up MARCoNS culture status was associated with longitudinal trajectories of α-MSH, compared with two additional biomarkers commonly assessed in this population: matrix metallopeptidase-9 (MMP-9) and vasoactive intestinal polypeptide (VIP). A total of 188 adult patients evaluated within a CIRS-informed clinical framework at a single clinical site were included. Each participant contributed two timepoints of laboratory data for α-MSH, MMP-9, and VIP, along with MARCoNS culture results. Results: Across the full cohort, α-MSH increased by an estimated 10 pg/mL, MMP-9 decreased by 398 ng/mL, and VIP increased by 20 pg/mL between baseline and follow-up. Mixed-effects modeling revealed a significant timepoint-by-MARCoNS interaction for α-MSH, such that patients who were MARCoNS-negative at follow-up exhibited higher circulating α-MSH levels compared with those who remained positive. In contrast, no corresponding MARCoNS interaction was observed for VIP or MMP-9. Discussion: These findings provide quantitative evidence that follow-up MARCoNS culture status is selectively associated with α-MSH trajectories in this retrospective cohort, supporting further prospective investigation into potential links between persistent bacterial nasal colonization and neuroendocrine-immune biomarkers in multisystem chronic illness.