Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to ColitisSummary

Yun Han Kwon; Huaqing Wang; Emmanuel Denou; Jean-Eric Ghia; Laura Rossi; Michelle E. Fontes; Steve P. Bernier; Md. Sharif Shajib; Suhrid Banskota; Stephen M. Collins; Michael G. Surette; Waliul I. Khan

Cellular and Molecular Gastroenterology and Hepatology (Jan 2019)

Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to ColitisSummary

Yun Han Kwon,
Huaqing Wang,
Emmanuel Denou,
Jean-Eric Ghia,
Laura Rossi,
Michelle E. Fontes,
Steve P. Bernier,
Md. Sharif Shajib,
Suhrid Banskota,
Stephen M. Collins,
Michael G. Surette,
Waliul I. Khan

Affiliations

Yun Han Kwon: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Huaqing Wang: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Emmanuel Denou: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Jean-Eric Ghia: University of Manitoba, Winnipeg, Manitoba, Canada
Laura Rossi: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Michelle E. Fontes: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Steve P. Bernier: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Md. Sharif Shajib: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Suhrid Banskota: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Stephen M. Collins: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Michael G. Surette: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Waliul I. Khan: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Correspondence Address correspondence to: Waliul I. Khan, Farncombe Family Digestive Health Research Institute, McMaster University Health Sciences Centre Room 3N7, 1280 Main Street W, Hamilton, Ontario, Canada. fax: (905) 522-3454.

Journal volume & issue: Vol. 7, no. 4
pp. 709 – 728

Abstract

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Background & Aims: Serotonin (5-hydroxytryptamine [5-HT]) is synthesized mainly within enterochromaffin (EC) cells in the gut, and tryptophan hydroxylase 1 (Tph1) is the rate-limiting enzyme for 5-HT synthesis in EC cells. Accumulating evidence suggests the importance of gut microbiota in intestinal inflammation. Considering the close proximity of EC cells and the microbes, we investigated the influence of gut-derived 5-HT on the microbiota and the susceptibility to colitis. Methods: Gut microbiota of Tph1-/- and Tph1+/- mice were investigated by deep sequencing. Direct influence of 5-HT on bacteria was assessed by using in vitro system of isolated commensals. The indirect influence of 5-HT on microbiota was assessed by measuring antimicrobial peptides, specifically β-defensins, in the colon of mice and HT-29 colonic epithelial cells. The impact of gut microbiota on the development of dextran sulfate sodium–induced colitis was assessed by transferring gut microbiota from Tph1-/- mice to Tph1+/- littermates and vice versa, as well as in germ-free mice. Results: A significant difference in microbial composition between Tph1-/- and Tph1+/- littermates was observed. 5-HT directly stimulated and inhibited the growth of commensal bacteria in vitro, exhibiting a concentration-dependent and species-specific effect. 5-HT also inhibited β-defensin production by HT-29 cells. Microbial transfer from Tph1-/- to Tph1+/- littermates and vice versa altered colitis severity, with microbiota from Tph1-/- mice mediating the protective effects. Furthermore, germ-free mice colonized with microbiota from Tph1-/- mice exhibited less severe dextran sulfate sodium–induced colitis. Conclusions: These findings demonstrate a novel role of gut-derived 5-HT in shaping gut microbiota composition in relation to susceptibility to colitis, identifying 5-HT–microbiota axis as a potential new therapeutic target in intestinal inflammatory disorders. Keywords: 5-Hydroxytryptamine (5-HT), Tph1, Microbiota, β-defensins, Colitis

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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