Strong decrease in biotin content may correlate with metabolic alterations in colorectal adenocarcinoma

Abstract

Short‐chain fatty acids are an important source of energy for colonocytes. One of these is propionate, which is metabolized through carboxylation by propionyl‐CoA carboxylase (PCC), an enzyme encoded by 2 genes, PCCA and PCCB. The co‐factor of this reaction is biotin, a product of intestinal bacterial metabolism, as is propionate. Despite detailed knowledge about the metabolic effects and physiology of biotin, the relative amounts of this vitamin in normal colonic mucosae and in tumour tissue remains quite unknown. The biotin content in normal and cancerous cells from the distal digestive tract was examined on 10 pairs of tissue specimens of colorectal cancer and adjacent normal mucosae using reflectance in situ hybridization (RISH). Having observed a high biotin content in colon mucosae and a low content in colorectal‐cancer cells, we then studied the transcription levels of PCCA and PCCB genes in 9 colorectal cancers and the corresponding mucosae. In all cases, the levels of mRNA were lower in colorectal cancers than in normal mucosae, the decrease being always more marked for PCCB than for PCCA. In normal mucosae and in adenocarcinoma cancer cells, PCCA and PCCB transcription levels were strongly related to the amount of biotin detected, but not to the number of chromosomes 13 (which carries PCCA) or 3 (which carries PCCB). Int. J. Cancer 72:768–775, 1997. © 1997 Wiley‐Liss, Inc.

Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells

“…However, our results seem to be confirmed by previous observations made in patients with colorectal cancer. Primary adenocarcinoma cells showed lower biotin concentration in comparison with normal mucosa cells and a reduction of transcript levels of the PCCA and PCCB genes (34).…”

Microbiome distinctions between the CRC carcinogenic pathways

“…26 An imbalance of butyrate, folate, and biotin-producing bacteria 27 could contribute to carcinogenesis as these molecules are involved in epithelial proliferation either directly or epigenetically. [28][29][30] Further, secondary bile acids may be carcinogenic by acting as mutagens, eliciting reactive oxygen species, and increasing NF-kappa B activation, resulting in inflammation. 31 Additionally, a diet low in fiber leaves the colon devoid of Microbiota Accessible Carbohydrates 32 and open for bacteria to feed on the protein-rich mucus layer that protects the colon epithelium.…”

Role of Dietary Micronutrients on Gut Microbial Dysbiosis and Modulation in Inflammatory Bowel Disease

“…[ 76 ] Relevant to the gut microbial metabolism is the B7‐dependent propionyl CoA carboxylase during the production of propionate. [ 77 ] The impact of B7 on gut bacterial growth and metabolism is not fully understood. Strains of propionibacteria showed growth dependency for B7 [ 65 ] as well as some strains of Lactobacillus in the absence of aspartic acid.…”