Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

Increased gut permeability in cancer cachexia: mechanisms and clinical relevance. Oncotarget. 2018 Apr 06;9(26):18224-18238 Authors: Bindels LB, Neyrinck AM, Loumaye A, Catry E, Walgrave H, Cherbuy C, Leclercq S, Van Hul M, Plovier H, Pachikian B, Bermúdez-Humarán LG, Langella P, Cani PD, Thissen JP, Delzenne NM Abstract Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium (Faecalibacterium prausnitzii) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and c...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research