Epigenetic effects of short-chain fatty acids from the large intestine on host cells

Abstract

Adult humans harbor at least as many microbial cells as eukaryotic ones. The largest compartment of this diverse microbial population, the gut microbiota, encompasses the collection of bacteria, archaea, viruses, and eukaryotic organisms that populate the gastrointestinal tract, and represents a complex and dynamic ecosystem that has been increasingly implicated in health and disease. The gut microbiota carries ∼100-to-150-times more genes than the human genome and is intimately involved in development, homeostasis, and disease. Of the several microbial metabolites that have been studied, short-chain fatty acids emerge as a group of molecules that shape gene expression in several types of eukaryotic cells by multiple mechanisms, which include changing histone acetylation, inducing DNA methylation, or through microRNA-mediated signaling. Butyric acid, one of the most extensively studied short-chain fatty acids, reaches higher concentrations in the colonic lumen, where it can be used as fuel by healthy colonocytes, than in the colonic crypts, where stem cells reside. In colon cancer cells, which preferentially metabolize glucose by glycolysis, butyric acid induces epigenetic modifications, leading to cell cycle progression inhibition and apoptosis. The lower butyrate concentration in the colonic crypts epigenetically inhibits negative regulators of the cell cycle, pointing towards the importance of the crypts in providing a protective niche for stem cells. A better understanding of the interface between the gut microbiota metabolites and epigenetic changes in eukaryotic cells promises to unravel in more detail processes that occur physiologically and, as part of disease, help develop novel biomarkers, and identify new therapeutic modalities.

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

“…In this regard, behavioral management therapy, cognitive behavioral therapy, speech language therapy, social skills training, and physical and nutritional therapies, as well treatments with medications for the alleviation of some symptoms, are common interventions [181]. The latter include the use of SSRI and tricyclic antidepressants, psychoactive or antipsychotic medications, stimulants, anxiolytics, and anticonvulsants [181,192]. Moreover, because oxidative stress, inflammation, and mitochondrial dysfunction are common pathophysiological mechanisms of ASD, drugs targeting these factors are being advocated [181].…”

“…Moreover, because oxidative stress, inflammation, and mitochondrial dysfunction are common pathophysiological mechanisms of ASD, drugs targeting these factors are being advocated [181]. In addition, probiotics, prebiotics, fecal microbiota transplantation, microbiota transfer therapy, antibiotics, and dietary adjustment methods may provide additional reliefs [181,[192][193][194].…”

How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer

“…This study also found that HF/HS feeding altered the methylation signature of histone in the mice. Many other studies have reported modulation of the post-translational modification of histones in colonic cells via microbiota-derived SCFAs, which led to differences in IBS [ 133 ].…”

The Effect of Maternal Probiotic or Synbiotic Supplementation on Sow and Offspring Gastrointestinal Microbiota, Health, and Performance

“…The modification of epigenetic landmarks, such as histone deacetylase and acyltransferase, modulate the host's gene expression. The current understanding and knowledge of epigenetic effects of SCFA on cells of the immune has been recently reviewed [108,109].…”