Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

Abstract

The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype.

The gut-bone axis: how bacterial metabolites bridge the distance

“…SCFAs affect the immune system by modifying gene expression profiles (68,69), cell chemotaxis (70,71), differentiation (54)(55)(56), proliferation (72)(73)(74), and apoptosis (75,76). In addition, SCFAs inhibit histone deacetylases (HDACs) and stimulate histone acetyltransferase (53, 56, 77, 78) ( Figure 1).…”

Abundance of Probiotics and Butyrate‐Production Microbiome Manages Constipation via Short‐Chain Fatty Acids Production and Hormones Secretion

“…Cells are affected by SCFAs, through binding to cell surface receptors which result in regulation of cell proliferation and differentiation. Individual SCFAs can enter cells through specific transporters and directly affect cellular metabolism, thus influencing cellular energy and signaling pathways . Studies have also found that SCFAs can modulate the immune response by regulating the size and function of the colonic Treg pool that can protect against colitis and intestinal inflammation in a FFAR2‐dependent manner in mice .…”

Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation

“…We show that the short-term (15–30 days) daily consumption of one high-fiber bar significantly increased the beneficial microbial metabolites SCFA, along with a durable change in the Firmicutes-to-Bacteroidetes ratio [ 17 ], up to 40 days after the dietary intervention stopped. This is of relevance, as it was shown that SCFAs affected the immune system during inflammatory diseases by modifying gene expression profiles [ 18 , 19 ], cell chemotaxis [ 20 , 21 ], differentiation [ 6 , 22 , 23 ], proliferation [ 24 , 25 , 26 ] and apoptosis [ 27 , 28 ]. In addition, SCFAs inhibit histone deacetylases (HDACs) and stimulate histone acetyltransferase [ 6 , 29 , 30 , 31 ].…”