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Gut microbiota-mediated immunomodulation in tumor.

ABSTRACT: Tumor immunity consists of various types of cells, which serve an important role in antitumor therapy. The gastrointestinal tract is colonized by trillions of microorganisms, which form the gut microbiota. In addition to pathogen defense and maintaining the intestinal ecosystem, gut microbiota also plays a pivotal role in various physiological processes. Recently, the association between these symbionts and cancer, ranging from oncogenesis and cancer progression to resistance or sensitivity to antitumor therapies, has attracted much attention. Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals. Moreover, modulation of microbiome could improve therapeutic response to immune checkpoint inhibitors (ICIs). These findings suggest that microbiome is involved in cancer pathogenesis and progression through regulation of tumor immunosurveillance, although the exact mechanisms remain largely unknown. This review focuses on the interaction between the microbiome and tumor immunity, with in-depth discussion regarding the therapeutic potential of modulating gut microbiota in ICIs. Further investigations are warranted before gut microbiota can be introduced into clinical practice.

SUBMITTER: Liu X

PROVIDER: S-EPMC8254267 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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Gut microbiota-mediated immunomodulation in tumor.

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