Trichinella spiralis infection remodels intestinal neurotransmitter metabolism during LPS-induced systemic inflammation.

Parasitic helminths can modulate host inflammatory responses, but whether this regulation involves remodeling of the intestinal neurochemical environment remains unclear. Here, we investigated whether Trichinella spiralis infection alters intestinal neurotransmitter-related metabolism during lipopolysaccharide (LPS)-induced systemic inflammation. In this study, we established an LPS-induced inflammatory model and a T. spiralis-infection with LPS challenge model. At 14 days after infection, mice were challenged with LPS, and inflammatory responses and duodenal neurotransmitter-related metabolites were assessed. T. spiralis infection reduced serum TNF-α and IL-1β levels and alleviated LPS-induced lung pathology. Targeted LC-MS/MS profiling revealed treatment-specific neurochemical signatures in duodenal tissues. Under basal conditions, T. spiralis infection increased histamine levels and reduced norepinephrine, 5-hydroxyindoleacetic acid, and xanthurenic acid. During LPS challenge, prior T. spiralis infection was associated with increased dopamine, epinephrine, levodopa, 5-hydroxytryptophan, histamine, and tyramine compared with LPS challenge alone. These changes suggest that T. spiralis infection remodels tyrosine-, histidine-, and tryptophan-related neurochemical pathways in the intestine. Receiver operating characteristic analysis further identified several metabolites that discriminated LPS-challenged mice from T. spiralis-infected, LPS-challenged mice, although these candidate signatures require validation in larger independent cohorts. Together, our findings indicate that intestinal neurochemical remodeling may represent a previously underappreciated component of helminth-associated anti-inflammatory regulation.