The Role of Short-Chain Fatty Acids and Bile Acids in Intestinal and Liver Function, Inflammation, and Carcinogenesis

Abstract

During the past decade, researchers have investigated the role of microbiota in health and disease. Recent findings support the hypothesis that commensal bacteria and in particular microbiota-derived metabolites have an impact on development of inflammation and carcinogenesis. Major classes of microbial-derived molecules such as short-chain fatty acids (SCFA) and secondary bile acids (BAs) were shown to have immunomodulatory potential in various autoimmune, inflammatory as well as cancerous disease models and are dependent on diet-derived substrates. The versatile mechanisms underlying both beneficial and detrimental effects of bacterial metabolites comprise diverse regulatory pathways in lymphocytes and non-immune cells including changes in the signaling, metabolic and epigenetic status of these. Consequently, SCFAs as strong modulators of immunometabolism and histone deacetylase (HDAC) inhibitors have been investigated as therapeutic agents attenuating inflammatory and autoimmune disorders. Moreover, BAs were shown to modulate the microbial composition, adaptive and innate immune response. In this review, we will discuss the recent findings in the field of microbiota-derived metabolites, especially with respect to the molecular and cellular mechanisms of SCFA and BA biology in the context of intestinal and liver diseases.

Regulatory role of short-chain fatty acids in inflammatory bowel disease

“…In addition, the extremely small size of the SCFAs allows them to enter the nucleus directly and act as inhibitors of histone deacetylase (HDAC) [ 55 ]. Histone acetylation is a process that can promote the loosening of the chromatin structure of target genes to enhance gene transcription, but HDAC inhibits this process [ 56 ].…”

Metabolomics of Breast Cancer: A Review

“…Hence, metabolomics study is important in categorizing breast cancer into different types and stages, as it uses accurate methods and requires less time for analysis. Metabolites from secondary bile acid metabolism, amino acid degradation, short-chain fatty acid production, and deconjugated hormones can be measured to predict tamoxifen resistance, hormone-induced apoptosis, cancer aggressiveness, and histone deacetylase (HDAC) inhibition [ 55 , 56 , 57 ].…”

Amelioratory Effect of Resistant Starch on Non-alcoholic Fatty Liver Disease via the Gut-Liver Axis

“…Mucin, in turn, promotes host-microbe symbiosis and enhances gut barrier integrity. Taken together, RS supplementation potentially regulates the release of various metabolites by symbiotic bacteria, including bioactive peptides, BAs, and EnEth, which are beneficial to the host as vital modulators of immunometabolism ( 62 – 66 ). This further indicated that dietary RSs can alleviate NAFLD through the GLA.…”