Autoimmune, Inflammatory, Autonomic and Enteric Measurements in Patients with Symptoms of Gastroparesis

Background/Objectives: Gastroparesis is a disorder in which individuals experience dysfunctional gastric motor symptoms, but the underlying etiology is unclear. This exploratory study investigates autoimmune, inflammatory, metabolic, autonomic, and enteric (AIMAE) abnormalities in patients with gastroparesis symptoms to provide new insights into pathophysiology. The aim of this study is to further elucidate the potential associations between the different AIMAE measurements. Methods: Twenty-one patients with gastroparesis symptoms underwent a series of testing including assays for measurement of autoimmune, inflammatory, and metabolic markers; measurement of the autonomic nervous system; electrogastrography recordings; and gastric emptying measurements. Associations were evaluated using Spearman’s rank correlation with pairwise-complete observations. Benjamini–Hochberg false-discovery-rate correction was applied separately within each prespecified statistical family, with q ≤ 0.05 defining statistical significance. Results: Across 3432 planned correlations in 10 prespecified families, four associations met the false-discovery-rate threshold. DFS-70 was positively associated with C-peptide (q= 0.000330). Low-resolution EGG S1 mean amplitude was positively associated with insulin (q = 0.000172). IL-6 was inversely associated with baseline sympathetic LFa modulation (q = 0.000172) and standing sympathetic LFa modulation (q = 0.000172). Conclusions: This prospective pilot study identified strong associations among autoimmune, inflammatory, metabolic, enteric, and autonomic measurements. The findings were robust to leave-one-out analyses and generally retained their direction and magnitude after excluding participants with diabetes or a gastric electrical stimulator. However, the results of this study should be interpreted as hypothesis-generating rather than causal due to its limitations including a small cohort and incomplete confounder information.