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

  • Stomach and Duodenum (J Pisegna and J Benhammou, Section Editors)
  • Published:
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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.

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Funding

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.

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Authors and Affiliations

  1. West Los Angeles VAMC, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA

    Mari Iwasaki, Yasutada Akiba & Jonathan D. Kaunitz

  2. Department of Medicine, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90073, USA

    Yasutada Akiba & Jonathan D. Kaunitz

  3. Department of Surgery, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90073, USA

    Jonathan D. Kaunitz

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  1. Mari Iwasaki
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  2. Yasutada Akiba
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  3. Jonathan D. Kaunitz
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Correspondence to Jonathan D. Kaunitz.

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Iwasaki, M., Akiba, Y. & Kaunitz, J.D. Duodenal Chemosensing of Short-Chain Fatty Acids: Implications for GI Diseases. Curr Gastroenterol Rep 21, 35 (2019). https://doi.org/10.1007/s11894-019-0702-9

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