Qing Li1,2,3, Wei Wu4, Dexin Gong1,2,3, Renduo Shang1,2,3, Jing Wang1,2,3, Honggang Yu5,6,7. 1. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. 2. Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. 3. Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Jiefang Rd. 238, Wuhan, 430060, People's Republic of China. 4. Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China. 5. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. yuhonggang@whu.edu.cn. 6. Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. yuhonggang@whu.edu.cn. 7. Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Jiefang Rd. 238, Wuhan, 430060, People's Republic of China. yuhonggang@whu.edu.cn.
Abstract
OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) could not completely prevent the progression of gastric cancer (GC), suggesting that non-H. pylori bacteria may participate in the carcinogenesis of GC. The dysbiosis of microbiota in the stomach of GC has gradually been investigated, while the detailed mechanism that promotes GC in this process has not been elucidated. We aimed to identify a non-H. pylori bacteria that contribute to GC. DESIGN: GC tissues and adjacent normal tissues were collected to identify bacteria that significantly increased in GC tissues by 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) analysis. CCK8, wound healing assay, and trans-well assay were performed to analyze the tumor-promoting effect of this bacteria. Next, we detailed the mechanism for tumor-promoting effect of the bacteria by immunofluorescence, RT-qPCR, and western-blotting analysis. RESULTS: Comparing the microbial community from GC tissues and adjacent normal tissues, we found that Propionibacterium acnes (P. acnes) significantly increased in GC tissues, especially in H. pylori-negative tissues. We further found that the abundance of P. acnes correlated with TNM stages of GC patients. Interestingly, condition medium (CM) from P. acnes-primed macrophages promoted migration of GC cells, while P. acnes only could not. We next proved that P. acnes triggers M2 polarization of macrophages via TLR4/PI3K/Akt signaling. CONCLUSIONS: Together, our finding identified that P. acnes could be a possible agent for the progression of GC besides H. pylori. M2 polarization of macrophages could be promoted by P. acnes via TLR4/PI3K/Akt signaling, thus triggers the progression of GC.
OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) could not completely prevent the progression of gastric cancer (GC), suggesting that non-H. pylori bacteria may participate in the carcinogenesis of GC. The dysbiosis of microbiota in the stomach of GC has gradually been investigated, while the detailed mechanism that promotes GC in this process has not been elucidated. We aimed to identify a non-H. pylori bacteria that contribute to GC. DESIGN: GC tissues and adjacent normal tissues were collected to identify bacteria that significantly increased in GC tissues by 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) analysis. CCK8, wound healing assay, and trans-well assay were performed to analyze the tumor-promoting effect of this bacteria. Next, we detailed the mechanism for tumor-promoting effect of the bacteria by immunofluorescence, RT-qPCR, and western-blotting analysis. RESULTS: Comparing the microbial community from GC tissues and adjacent normal tissues, we found that Propionibacterium acnes (P. acnes) significantly increased in GC tissues, especially in H. pylori-negative tissues. We further found that the abundance of P. acnes correlated with TNM stages of GC patients. Interestingly, condition medium (CM) from P. acnes-primed macrophages promoted migration of GC cells, while P. acnes only could not. We next proved that P. acnes triggers M2 polarization of macrophages via TLR4/PI3K/Akt signaling. CONCLUSIONS: Together, our finding identified that P. acnes could be a possible agent for the progression of GC besides H. pylori. M2 polarization of macrophages could be promoted by P. acnes via TLR4/PI3K/Akt signaling, thus triggers the progression of GC.
Authors: Jennifer L Lofgren; Mark T Whary; Zhongming Ge; Sureshkumar Muthupalani; Nancy S Taylor; Melissa Mobley; Amanda Potter; Andrea Varro; Daniel Eibach; Sebastian Suerbaum; Timothy C Wang; James G Fox Journal: Gastroenterology Date: 2010-10-13 Impact factor: 22.682
Authors: Benjamin Chun-Yu Wong; Shiu Kum Lam; Wai Man Wong; Jian Shun Chen; Ting Ting Zheng; Rui E Feng; Kam Chuen Lai; Wayne Hsing Cheng Hu; Siu Tsan Yuen; Suet Yi Leung; Daniel Yee Tak Fong; Joanna Ho; Chi Kong Ching; Jun Shi Chen Journal: JAMA Date: 2004-01-14 Impact factor: 56.272
Authors: Chung-Wei Lee; Barry Rickman; Arlin B Rogers; Zhongming Ge; Timothy C Wang; James G Fox Journal: Cancer Res Date: 2008-04-25 Impact factor: 12.701
Authors: Kvin Lertpiriyapong; Mark T Whary; Sureshkumar Muthupalani; Jennifer L Lofgren; Eric R Gamazon; Yan Feng; Zhongming Ge; Timothy C Wang; James G Fox Journal: Gut Date: 2013-06-28 Impact factor: 23.059
Authors: Jennifer M Noto; Joseph P Zackular; Matthew G Varga; Alberto Delgado; Judith Romero-Gallo; Matthew B Scholz; M Blanca Piazuelo; Eric P Skaar; Richard M Peek Journal: mBio Date: 2019-05-28 Impact factor: 7.867
Authors: Rui M Ferreira; Joana Pereira-Marques; Ines Pinto-Ribeiro; Jose L Costa; Fatima Carneiro; Jose C Machado; Ceu Figueiredo Journal: Gut Date: 2017-11-04 Impact factor: 23.059