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

  • Mari Iwasaki
  • Yasutada Akiba
  • Jonathan D. KaunitzEmail author
Stomach and Duodenum (J Pisegna and J Benhammou, Section Editors)
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Part of the following topical collections:
  1. Topical Collection on Stomach and Duodenum

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-HT3 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.

Keywords

Short-chain fatty acid receptors Glucagon-like peptide-2 Serotonin Mucosal defense Nutrition sensing 

Notes

Funding Information

This work was supported by a Department of Veterans Affairs Merit Review Award and National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-54221.

Compliance With Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  • Mari Iwasaki
    • 1
  • Yasutada Akiba
    • 1
    • 2
  • Jonathan D. Kaunitz
    • 1
    • 2
    • 3
    Email author
  1. 1.West Los Angeles VAMCLos AngelesUSA
  2. 2.Department of Medicine, The David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA
  3. 3.Department of Surgery, The David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

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