부산대학교 도서관

The hygiene hypothesis proposes that decreased exposure to infectious agents in developed countries may contribute to the development of allergic and autoimmune diseases. Trichinella spiralis, a parasitic roundworm, causes trichinellosis, also known as trichinosis, in humans. T. spiralis had many hosts, and almost any mammal could become infected. Adult worms lived in the small intestine, while the larvae lived in muscle cells of the same mammal. T. spiralis was a significant public health threat because it could cause severe illness and even death in humans who eat undercooked or raw meat containing the parasite. The complex interactions between gastrointestinal helminths, gut microbiota, and the host immune system present a challenge for researchers. Two groups of mice were infected with T. spiralis vs uninfected control, and the experiment was conducted over 60 days. The 16S rRNA gene sequences and untargeted LC/MS-based metabolomics of fecal and serum samples, respectively, from different stages of development of the Trichinella spiralis-mouse model, were examined in this study. Gut microbiota alterations and metabolic activity accompanied by parasite-induced immunomodulation were detected. The inflammation parameters of the duodenum (villus/crypt ratio, goblet cell number and size, and histological score) were involved in active inflammation and oxidative metabolite profiles. These profiles included increased biosynthesis of phenylalanine, tyrosine, and tryptophan while decreasing cholesterol metabolism and primary and secondary bile acid biosynthesis. These disrupted metabolisms adapted to infection stress during the enteral and parenteral phases and then return to homeostasis during the encapsulated phase. There was a shift from an abundance of Bacteroides in the parenteral phase to an abundance of probiotic Lactobacillus and Treg-associated-Clostridia in the encapsulated phase. Th2 immune response (IL-4/IL-5/IL-13), lamina propria Treg, and immune hyporesponsiveness metabolic pathways (decreased tropane, piperidine and pyridine alkaloid biosynthesis and biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid) were all altered. These findings enhanced our understanding of gut microbiota and metabolic profiles of Trichinella -infected mice, which could be a driving force in parasite-shaping immune system maintenance. Author summary: The complex interactions between gastrointestinal helminths, gut microbiota, and the host immune system are unknown. Here, we studied stool and serum samples from Trichinella-infected mice at different stages of development by 16S rRNA gene sequencing and non-targeted LC/MS metabolomics. We found that there is abundant Bacteroides in the gut microbiota during the parenteral phase of Trichinella infection, and the encapsulated phase shifts to a large number of probiotics Lactobacillus and Treg-associated-Clostridia. Metabolic activities also change in the enteral and parenteral phases, such as abnormal cholesterol metabolism. It is accompanied by changes in the Th2 immune response, lamina propria Treg, and immune hypo-responsiveness metabolic pathways. These findings contribute to a better understanding of the complex interactions between gastrointestinal helminths, gut microbiota, and host immune system. And the system-level knowledge of parasite metabolism and gene regulation through multi-omics joint analysis can help identify new targets for anthelmintic drugs and develop metabolite-based diagnostic tools. [ABSTRACT FROM AUTHOR]