A Purified Membrane Protein from or the Pasteurised Bacterium Blunts Colitis Associated Tumourigenesis by Modulation of CD8 T Cells in Mice

Overview

Journal Gut

Specialty Gastroenterology

Date 2020 Mar 15

PMID 32169907

Citations 224

Authors

Lijuan Wang

Lei Tang

Yiming Feng

Suying Zhao

Mei Han

Chuan Zhang

Gehui Yuan

Jun Zhu

Shuyuan Cao

Qian Wu

Lei Li

Zhan Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). () is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how engages the immune response in CAC.

Design: Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of or Amuc_1100 on the immune response in acute colitis and CAC were investigated.

Results: was significantly reduced in patients with IBD and mice with colitis or CAC. or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8 cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32 macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1 CTLs in the spleen. Moreover, and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium.

Conclusions: These data indicate that pasteurised or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.

Citing Articles

Pasteurized Timepie001 ameliorates DSS-induced ulcerative colitis in mice by alleviating intestinal injury and modulating gut microbiota.

Han H, Xiong H, Liu Z, Liu X, Wang H, Kou J Front Microbiol. 2025; 16:1542522.

PMID: 40046294 PMC: 11880272. DOI: 10.3389/fmicb.2025.1542522.

Gut dysbiosis conveys psychological stress to activate LRP5/β-catenin pathway promoting cancer stemness.

Cui B, Luo H, He B, Liu X, Lv D, Zhang X Signal Transduct Target Ther. 2025; 10(1):79.

PMID: 40038255 PMC: 11880501. DOI: 10.1038/s41392-025-02159-1.

Akkermansia muciniphila: promises and pitfallsfor next-generation beneficial microorganisms.

Liu Y, Li Z, Lee S, Chen S, Li F Arch Microbiol. 2025; 207(4):76.

PMID: 40032707 DOI: 10.1007/s00203-025-04263-w.

Big lessons from the little in hepatocellular carcinoma.

Yang Y, Shi X Front Immunol. 2025; 16:1524563.

PMID: 40028328 PMC: 11868108. DOI: 10.3389/fimmu.2025.1524563.

The Urogenital System Microbiota: Is It a New Gamechanger in Urogenital Cancers?.

Ece G, Aktas A, Caner A, Saglik I, Kula Atik T, Ulusan Bagci O Microorganisms. 2025; 13(2).

PMID: 40005682 PMC: 11858393. DOI: 10.3390/microorganisms13020315.

References

Yassour M, Lim M, Yun H, Tickle T, Sung J, Song Y . Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016; 8(1):17. PMC: 4756455. DOI: 10.1186/s13073-016-0271-6. View

Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S . Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019; 25(7):1096-1103. PMC: 6699990. DOI: 10.1038/s41591-019-0495-2. View

Dao M, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger E . Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2015; 65(3):426-36. DOI: 10.1136/gutjnl-2014-308778. View

Lee J, Lyons P, McKinney E, Sowerby J, Carr E, Bredin F . Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest. 2011; 121(10):4170-9. PMC: 3196314. DOI: 10.1172/JCI59255. View

Yassin M, Sadowska Z, Djurhuus D, Nielsen B, Tougaard P, Olsen J . Upregulation of PD-1 follows tumour development in the AOM/DSS model of inflammation-induced colorectal cancer in mice. Immunology. 2019; 158(1):35-46. PMC: 6700467. DOI: 10.1111/imm.13093. View

Ngiow S, Young A, Jacquelot N, Yamazaki T, Enot D, Zitvogel L . A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1. Cancer Res. 2015; 75(18):3800-11. DOI: 10.1158/0008-5472.CAN-15-1082. View

Wang Z, Vaughan T, Zhu W, Chen Y, Fu G, Medrzycki M . Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8 T-Cell Activation. Front Immunol. 2019; 10:486. PMC: 6431666. DOI: 10.3389/fimmu.2019.00486. View

Zhang T, Li Q, Cheng L, Buch H, Zhang F . Akkermansia muciniphila is a promising probiotic. Microb Biotechnol. 2019; 12(6):1109-1125. PMC: 6801136. DOI: 10.1111/1751-7915.13410. View

Carr P, Weigl K, Jansen L, Walter V, Erben V, Chang-Claude J . Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk. Gastroenterology. 2018; 155(6):1805-1815.e5. PMC: 6279591. DOI: 10.1053/j.gastro.2018.08.044. View

10.

Everard A, Belzer C, Geurts L, Ouwerkerk J, Druart C, Bindels L . Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013; 110(22):9066-71. PMC: 3670398. DOI: 10.1073/pnas.1219451110. View

11.

Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z . Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015; 6:6528. DOI: 10.1038/ncomms7528. View

12.

Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L . A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016; 23(1):107-113. DOI: 10.1038/nm.4236. View

13.

Tanoue T, Morita S, Plichta D, Skelly A, Suda W, Sugiura Y . A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019; 565(7741):600-605. DOI: 10.1038/s41586-019-0878-z. View

14.

Yang Y, Weng W, Peng J, Hong L, Yang L, Toiyama Y . Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-κB, and Up-regulating Expression of MicroRNA-21. Gastroenterology. 2016; 152(4):851-866.e24. PMC: 5555435. DOI: 10.1053/j.gastro.2016.11.018. View

15.

Thomas D, Massague J . TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell. 2005; 8(5):369-80. DOI: 10.1016/j.ccr.2005.10.012. View

16.

Ring C, Klopfleisch R, Dahlke K, Basic M, Bleich A, Blaut M . Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice. Gut Microbes. 2018; 10(2):188-203. PMC: 6546315. DOI: 10.1080/19490976.2018.1511663. View

17.

Miller R, HOSKINS L . Mucin degradation in human colon ecosystems. Fecal population densities of mucin-degrading bacteria estimated by a "most probable number" method. Gastroenterology. 1981; 81(4):759-65. View

18.

Li H, van der Leun A, Yofe I, Lubling Y, Gelbard-Solodkin D, van Akkooi A . Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma. Cell. 2019; 176(4):775-789.e18. PMC: 7253294. DOI: 10.1016/j.cell.2018.11.043. View

19.

Baxter N, Zackular J, Chen G, Schloss P . Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome. 2014; 2:20. PMC: 4070349. DOI: 10.1186/2049-2618-2-20. View

20.

Zhai R, Xue X, Zhang L, Yang X, Zhao L, Zhang C . Strain-Specific Anti-inflammatory Properties of Two Strains on Chronic Colitis in Mice. Front Cell Infect Microbiol. 2019; 9:239. PMC: 6624636. DOI: 10.3389/fcimb.2019.00239. View