The role of Parvimonas micra in intestinal tumorigenesis in germ-free and conventional APC min/+ mice

• Published in: Journal of clinical oncology Vol. 37; no. 4_suppl; p. 531
• Main Authors: Yu, Jun, Zhao, Liuyang, Zhao, Risheng, Long, Xiaohang, Coker, Olabisi Oluwabukola, Sung, Joseph J.Y.
• Format: Journal Article
• Language: English
• Published: 01.02.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.4_suppl.531

Abstract only 531 Background: Our in-house meta-analysis of fecal shotgun metagenomic sequences from colorectal cancer (CRC) and control subjects from four cohorts of various ethnicities identified a higher abundance of Parvimonas micra in CRC. We aimed to investigate the effect of P. micra in colon tumor formation and development. Methods: We collected 309 fecal samples and 259 colon biopsies from patients with CRC, advanced adenoma and healthy subjects. P. micra strain was isolated from the feces of a CRC patient. APC min/+ mice and germ-free (GF) mice were orally gavaged with P. micra, or Esherichia coli. Colon epithelial cell line NCM460 and cancer cell lines HT-29 and Caco-2 were exposed to P. micra or E. coli conditional medium. Results: P. micra was significantly enriched both in the feces (n = 207, p < 0.01) and tissue biopsies (n = 99, p < 0.01) of CRC patients compared with controls (n = 102 for fecal samples, n = 160 for tissues biopsies). APC min/+ mice gavaged with P. micra exibited significantly higher tumor burden ( p < 0.01) and tumor load ( p < 0.01), compared to mice gavaged with either E. coli or non-bacterial control. Consistently, cell proliferation was significantly higher in the colon tissues of P. micra gavaged GF mice relative to control mice evidenced by increased Ki-67 positive cells ( p < 0.05) and PCNA protein expression ( p < 0.01) at weeks 20 and 32. In line with this, colon cell lines NCM460, HT-29 and Caco-2 exposed to P. micra conditional medium significantly increased proliferation than control group (all p < 0.05). Flow cytometry analyses showed that Th2 and Th17 cells were markedly increased, while Th1 were reduced in the lamina propria of the colon tissues of P. micra gavaged mice compared to control mice (all p < 0.01) . Consistently, P. micra colonization in GF mice was associated with increased expression of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-12 (all p < 0.01). Conclusions: The abundance of P. micra was significantly increased in the feces and tissue biopsies of CRC patients. P. micra promotes intestinal carcinogenesis in APC min/+ mice and increase cell proliferation in GF mice. The tumor promoting effect of P. micra is associated with altered immune responses and enhanced inflammation in the gut.