Influence of a Low‐Carbohydrate High‐Fat Diet on Peritoneal Inflammation, Cancer‐Associated Lymphocytes, and Survival in a Murine Carcinomatous Peritonitis Model

Abstract

Background Low‐carbohydrate high‐fat diets (LCHFDs) are thought to be beneficial for metabolic support in patients with advanced cancer. However, whether LCHFDs affect the progression of carcinomatous peritonitis (CP) remains unclear. Our study examined the influence of a lard‐based LCHFD on host immunity and survival in a murine CP model. Methods Mice were fed either a normal diet (ND) or an LCHFD ad libitum. On day 7, Panc02 cancer cells were inoculated intraperitoneally. Mice were killed on days 7, 21, and 35, and cytokine levels in the peritoneal fluid, as well as the number and phenotypes of peritoneal, splenic, and tumor‐infiltrating lymphocytes were measured. Survival studies were performed with both ad libitum and isocaloric feeding in other sets of mice. Results The levels of all cytokines significantly increased in the LCHFD group compared with those in the ND group on day 21. The tumor necrosis factor α and interleukin‐10 levels were higher in the LCHFD group than in the ND group on day 35. In the LCHFD group, the regulatory T‐cell (Treg) number was significantly higher in the peritoneal cavity and tumor. The survival times were worse in the LCHFD group than in the ND group. Conclusion The ad libitum, lard‐based LCHFD feeding of CP mice increases the peritoneal cytokine levels, which may reduce splenic, anticancer lymphocytes and increase the number of Tregs in the peritoneal cavity and tumor. The detrimental effects of LCHFD are linked to dietary composition rather than overfeeding.

Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development

“…To our knowledge, only one study has investigated the impact of a ketogenic diet over 3 weeks on Treg induction in humans ( 64 ). Data in mice are inconsistent depending on the model with either an increase in Tregs in a carcinomatous peritonitis model ( 65 ) or a decrease in a diabetic obese mouse ( 66 ). This difference may be due to the altered metabolic status of the mice.…”