Intestinal mucosal barrier damage and the development of cachexia in colon cancer patients

Abstract

Objective To investigate the association of bacterial translocation (BT) with cachexia in colonic cancer patients. Methods From September 2015 to May 2017 the clinical data of 292 colon cancer patients were studied at Qingdao Municipal Hospital. The bacteria in peripheral blood and mesenteric lymph nodes were detected by bacterial culture, and the bacterial DNA in peripheral blood was detected by PCR technique to determine the occurrence of bacterial translocation. Intestinal epithelial T-cell subsets and NK cells were evaluated using flow cytometry. Western blot and immunofluorescence were used to check tight junction proteins Occludin, Claudins-2, Zonula occluden-2 in intestinal epithelium. Fluorescence in situ hybridization and immunohistochemistry were used to detect the translocated bacteria and endotoxin. Results Compared with noncachectic patients, cachectic patients had a significantly higher BT ratio (27.8% vs. 7.2%, χ2=20.871, P< 0.001). BT in the intestinal mucus layer was associated with lower levels of T-cell subsets and NK cells in the intestinal epithelium in BT(+ ) patients (CD3+ T: 36.69%±5.87% vs. 41.63%±5.03%, CD4+ T: 44.08%±5.12% vs. 49.58%±7.01%, CD8+ T: 65.68%±5.51% vs. 61.43%±5.58%, CD4+ T/CD8+ T: 0.71%±0.21% vs. 0.91%±0.23%, NK: 27.86%±3.93% vs. 34.69%±4.52%, all P< 0.01). Endotoxin was detected within the small intestinal wall in BT(+ ) patients and claudin-2 expression increased (0.63±0.13 vs. 0.21±0.06, t=-2.936, P<0.01), whereas Occludin and Zonula occluden-2 expressions decreased(0.37±0.13 vs. 0.84±0.17, 0.16±0.07 vs. 0.58±0.19, t=2.151, 2.111, both P<0.05). Conclusions BT may contribute to the development of colon cancer cacheria, and tight junction could be the gateway of BT. Key words: Colonic neoplasms; Cachexia; Claudins; Bacterial translocation