Duodenal Chemosensing of Short-Chain Fatty Acids: Implications for GI Diseases

Abstract

Purpose of Review-Short-chain fatty acids (SCFAs), the main bacterial fermentation products in the hindgut of hindgut fermenters, are also present in the foregut lumen. We discuss the impact of SCFAs in the duodenal defense mechanisms and in the gastrointestinal (GI) pathogenesis. Recent Findings-Luminal SCFAs augment the duodenal mucosal defenses via release of serotonin (5-HT) and glucagon-like peptide-2 (GLP-2) from enteroendocrine cells. Released GLP-2 protects the small intestinal mucosa from nonsteroidal anti-inflammatory drug-induced enteropathy. SCFAs are also rapidly absorbed via SCFA transporters and interact with afferent and myenteric nerves. Excessive SCFA signals with 5-HT 3 receptor overactivation may be implicated in the pathogenesis of irritable bowel syndrome symptoms. SCFA production exhibits diurnal rhythms with host physiological responses, suggesting that oral SCFA treatment may adjust the GI clocks. Summary-SCFAs are not only a source of energy but also signaling molecules for the local regulation of the GI tract and systemic regulation via release of gut hormones. Targeting SCFA signals may be a novel therapeutic for GI diseases and metabolic syndrome.

The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics

“…Microbial enzymes can also metabolize dietary precursors for host neurotransmitter synthesis (for example, tryptophan (for serotonin) and tyrosine (for dopamine)), reducing their bioavailability 111 . In addition, microbial metabolites, such as SCFAs, if present in a sufficient quantity in the postbiotic preparation, could stimulate enterochromaffin cells to produce serotonin, which can subsequently enter the bloodstream 112 . A study in mice and human enteroids using live and heat-killed Bifidobacterium dentium has highlighted that viability is crucial for serotonin induction by this microorganism 113 , so that it remains to be investigated whether postbiotic preparations other than heat-killed preparations could exert this effect.…”

Duodenal microbiome in patients with or without Helicobacter pylori infection

“…Here, the abundance of food substrates, digestive enzymes, and bile acids is in close contact with the local microbiota potentially modulating its composition 10 . The intermittent presence of substrates, such as food and microbes in the SI, determines changes within the intestinal lumen and stimulates the release of intestinal hormones associated with gastrointestinal as well as systemic metabolic and immune functions that can potentially modulate the SI microbiota 11 . This changing scenario differs from the more stable one in the large intestine where intestinal content loses water and is stored until evacuation every 24 hours or longer.…”

Xiao Cheng Qi Decoction, an Ancient Chinese Herbal Mixture, Relieves Loperamide-Induced Slow-Transit Constipation in Mice: An Action Mediated by Gut Microbiota

“…In response to SCFAs, the enterochromaffin cell releases 5-HT, which activates 5-HT3 receptors on vagal sensory fibers and causes muscular contraction [ 32 ]. The release of 5-HT from enterochromaffin cells was shown to be mediated by the activation of GPR43, a receptor for SCFAs [ 33 ]. These results imply that the profile of gut microbiota and the level of SCFAs are strongly correlated with 5-HT signaling.…”