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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.
Highlights
The metabolism of the human microbiota is intimately linked with that of the host, especially in mucosal tissues like the gut or the nasopharynx
The observed pattern of Epstein-Barr virus (EBV) lytic genes was not due to decrease of pH due to the exposure to acids, as in cells treated with low molarity of hydrochloric acid (HCl), with comparable pK, we did not observe induction of EBV IE genes expression (Fig 1, lanes 3–4)
We took the advantage of a recombinant EBV virus, which carries the gene for green fluorescent protein (GFP)
Summary
The metabolism of the human microbiota is intimately linked with that of the host, especially in mucosal tissues like the gut or the nasopharynx. One important product of this metabolism is the production of short-chain fatty acids (SCFAs), which can have local effects at the site of production as well as systemic ones, through blood circulation [4,5]. SCFAs refer to free fatty acids with short (less than 6 carbons) aliphatic chains. They include formic acid, valeric acid, caproic acid and butyric acid and its structural isomers [6]. N-Butyric acid is a 4-carbon straight chain SCFA, most interesting due to its high production by the microbiota. It reaches a concentration of 20mM in the colon. The metabolism of butyrate (salt of butyric acid) has been estimated to provide about 50% of the daily energy requirements of the gastrointestinal mucosa [8,9]
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