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

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.

Influences of Short-Term Fasting and Carbohydrate Supplementation on Gut Immunity and Mucosal Morphology in Mice.

BACKGROUND: Preoperative carbohydrate (CHO) supplementation has been recommended in enhanced recovery after surgery protocols. However, the effects of CHO supplementation on gut and systemic immunity are not well understood. METHODS: Mice (n = 60) were randomized to 1 of the following 5 groups: control (ad lib feeding), 12-hour fasting without CHO administration (fasting), and 12 hours of fasting with CHO administration at 2, 4, and 8 hours before sacrifice. Then, lymphocytes were isolated from gut-associated lymphoid tissue, that is, Peyer's patches, the intraepithelial space, and the lamina propria of the small intestine. These lymphocyte numbers and phenotypes were evaluated. IgA levels in respiratory and small-intestinal washings were determined by ELISA. Morphology, proliferation, and apoptosis of the intestinal epithelium were also evaluated histologically. RESULTS: Although there were no significant differences in IgA levels among the 5 groups, fasting decreased intraepithelial and lamina propria, but not Peyer's patches lymphocyte numbers. CHO at 2 hours prevented lymphocyte loss in intraepithelial, whereas CHO at 4 hours reversed lamina propria lymphocytes numbers. Percentages of lymphocyte phenotypes were similar in each site among the 5 groups. Fasting caused villous atrophy; however, CHO at 2 hours restored villous structure along with maintenance of epithelial cell proliferation rate. CONCLUSIONS: Only 12 hours of fasting causes marked gut-associated lymphoid tissue cell loss along with gut atrophy. However, CHO at 2 hours preserves gut immunity and morphology not completely but moderately.