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Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response.

ABSTRACT: Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic CD8+ T cells and on IFN-?. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.

SUBMITTER: Uribe-Herranz M

PROVIDER: S-EPMC6934221 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response.

Uribe-Herranz Mireia M Rafail Stavros S Beghi Silvia S Gil-de-Gómez Luis L Verginadis Ioannis I Bittinger Kyle K Pustylnikov Sergey S Pierini Stefano S Perales-Linares Renzo R Blair Ian A IA Mesaros Clementina A CA Snyder Nathaniel W NW Bushman Frederic F Koumenis Constantinos C Facciabene Andrea A

The Journal of clinical investigation 20200101 1

Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteri ...[more]

PMID: 31815742

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Project description:Antibiotics are widely used in gastrointestinal diseases in meat rabbit breeding, which causes safety problems for meat products. Dietary fiber can regulate the gut microbiota of meat rabbits, but the mechanism of improving meat quality is largely unknown. The objective of this study was to evaluate the effects of adding different fiber sources to rabbit diets on the growth performance, gut microbiota composition, and muscle metabolite composition of meat rabbits. A total of 18 New Zealand white rabbits of similar weight (40 ± 1 day old) were randomly assigned to beet pulp treatment (BP), alfalfa meal treatment (AM), and peanut vine treatment (PV). There were 6 repeats in each treatment and all were raised in a single cage. The predictive period was 7 days and the experimental period was 40 days. The results revealed that AM and PV supplementation increased growth performance, slaughter performance, and intestinal development of meat rabbits compared with the BP treatment, and especially the effect of AM treatment was better. The content of butyric acid was increased in PV and AM treatments compared with the BP treatment. The expression of mitochondrial biosynthesis genes of liver, cecum, and muscle showed that AM treatment increased gene expression of CPT1b compared to the BP treatment. In addition, AM and PV treatments significantly increased the microbial diversity and richness compared with BP treatment, and their bacterial community composition was similar, and there were some differences between AM and PV treatments and BP treatment. Metabonomics analysis of muscle showed that AM treatment significantly increased amino acid and fatty acid metabolites compared with BP treatment, which were mainly concentrated in energy metabolism, amino acid metabolism, and fatty acid regulation pathways. Furthermore, through correlation analysis, it was found that there was a significant correlation between rumenococci in the cecum and amino acid metabolites in the muscle. Overall, these findings indicate that AM may affect the body's health by changing its gut microbiota, and then improving meat quality, and the intestinal-muscle axis provides a theoretical basis.

Dataset Information

Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response.

Publications

Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response.

Similar Datasets

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