Specific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression

Abstract

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

Multivariate logistic regression analysis of the clinical factors influencing locally advanced prostate cancer

“…The PCa level is closely related to age ( 22 ), levels of androgens ( 23 ), genetics ( 24 ) and obesity ( 25 ). Increasing evidence suggests obesity to be associated with an increased incidence of aggressive PCa ( 9 , 10 , 26 - 30 ) as well as an increased risk of biochemical failure following radical prostatectomy ( 31 ) and external-beam radiotherapy ( 32 ), Such results may be associated with a higher prevalence of complications following androgen-deprivation therapy, increased PCa-specific mortality, and difficulties in the treatment of obese men. Obesity may have an impact on the development and progression of PCa by influencing levels of adipokines ( 33 ), testosterone ( 23 ), and systemic inflammation ( 34 ).…”

Potential role of gut microbiota in prostate cancer: immunity, metabolites, pathways of action?

“…In addition, when FMT containing CRPC feces was injected into mice, it was found that the expression of DNA-PKcs, RAD51, and LPCAT1 in the prostate tissue of mice was positively correlated with the malignant degree of PCa ( 60 ). Sphingosine 1-phosphate receptor 2 ( S1PR2 ) is a gene mainly regulated by a HFD, which is associated with abundantbody mass index, Lactobacillus, a low BMI and aggressive characteristics in patients with PCa ( 110 ). Additionally, S1PR2 expression is seen in host endothelial cells and tumor-infiltrating bone marrow cells, where it suppresses the expression of vascular endothelial growth factor and matrix metalloproteinase-9 activity to prevent tumor angiogenesis and tumor growth ( 111 ).…”

The pathophysiologic basis of prostate cancer review

“…Palliation of multiple areas of bone pain may be achieved by hemi body irradiation which occurs in two stages. Initially a single 6 Gy fraction is delivered to the upper half of the body and the same dose is administered six weeks later to the bottom half [34] . More recently, strontium has emerged as an alternative to hemi body irradiation.…”

“…Strontium localizes to the bone and the treatment is generally well tolerated. Its use though is limited by cost [34][35] .…”