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

Autor: Laura Rossi, Waliul I. Khan, Jean-Eric Ghia, Steve P. Bernier, Stephen M. Collins, Emmanuel Denou, Suhrid Banskota, Md. Sharif Shajib, Michelle E. Fontes, Huaqing Wang, Yun Han Kwon, Michael G. Surette
Rok vydání: 2019
Předmět:
Male
PPAR-γ
peroxisome proliferator-activated receptor gamma
0301 basic medicine
5-HTP
5-hydroxytryptophan
beta-Defensins
mBD
mouse β-defensin
MPO
myeloperoxidase
hBD
human β-defensin
Tryptophan Hydroxylase
DMSO
dimethyl sulfoxide
Gut flora
0302 clinical medicine
AMP
antimicrobial peptide
Intestinal Mucosa
Original Research
5-HT
5-hydroxytryptamine
TPH1
IBD
inflammatory bowel disease
biology
DNBS
dinitrobenzene sulfonic acid
Chemistry
Microbiota
Dextran Sulfate
Gastroenterology
qRT-PCR
quantitative real-time polymerase chain reaction
ELISA
enzyme-linked immunosorbent assay
Colitis
GI
gastrointestinal
Abx
antibiotics
Anti-Bacterial Agents
Up-Regulation
Intestines
ERK1/2
extracellular signal-regulated kinase-1 and -2
EC
enterochromaffin
PCoA
principal coordinate ordination
SCFA
short-chain fatty acid
Enterochromaffin cell
030211 gastroenterology & hepatology
Disease Susceptibility
Signal Transduction
Heterozygote
Serotonin
FDR
false discovery rate
Colon
Antimicrobial peptides
PBS
phosphate-buffered saline
Down-Regulation
GIL
gut isolate library
digestive system
Microbiology
03 medical and health sciences
Immune system
DSS
dextran sulfate sodium
Tph1
CD
Crohn’s disease
OTU
operational taxonomic unit
medicine
Animals
Germ-Free Life
EEC
enteric endocrine cell
lcsh:RC799-869
Tph
tryptophan hydroxylase
Inflammation
5-Hydroxytryptamine (5-HT)
Bacteria
β-defensins
Hepatology
Epithelial Cells
biology.organism_classification
medicine.disease
WT
wild-type
Gastrointestinal Microbiome
IL
interleukin
Mice
Inbred C57BL
PPAR gamma
GF
germ-free
OD
optical density
UC
ulcerative colitis
030104 developmental biology
Receptors
Serotonin
lcsh:Diseases of the digestive system. Gastroenterology
Zdroj: Cellular and Molecular Gastroenterology and Hepatology, Vol 7, Iss 4, Pp 709-728 (2019)
Cellular and Molecular Gastroenterology and Hepatology
ISSN: 2352-345X
DOI: 10.1016/j.jcmgh.2019.01.004
Popis: 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.
Graphical abstract
Databáze: OpenAIRE
Externí odkaz: