Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain Axis

Autor: Noah F. Shroyer, Amy C. Engevik, Sridevi Devaraj, Bradley T. Endres, Berkley Luck, James Versalovic, Heather A. Danhof, Faith D. Ihekweazu, Anne Hall, Zhongcheng Shi, Chonnikant Visuthranukul, Kevin W. Garey, Anthony M. Haag, Robert A. Britton, Sigmund J. Haidacher, Melinda A. Engevik, Alexandra Chang-Graham, Joseph M. Hyser, Thomas D. Horvath
Rok vydání: 2021
Předmět:
0301 basic medicine
FISH
fluorescence in situ hybridization
Cell Culture Techniques
Acetates
HIE
human intestinal enteroid
Mice
0302 clinical medicine
CFU
colony-forming unit
Brain-Gut Axis
LDM4
Lactic Acid Bacteria Defined Media 4
Intestinal Mucosa
SRM
selected reaction monitoring
qPCR
quantitative real-time polymerase chain reaction
Receptor
Serotonin transporter
Original Research
FA
formic acid
CM
conditioned media
Behavior
Animal
biology
Chemistry
Gastroenterology
NGN3
Neurogenin-3
GI
gastrointestinal
Serotonin Transporter
Bifidobacterium dentium
mRNA
messenger RNA
FFAR
free fatty acid receptor
Organoids
Models
Animal
SCFA
short-chain fatty acid
Enterochromaffin cell
LPS
lipopolysaccharide
030211 gastroenterology & hepatology
Serotonin
ChgA
chromogranin A
PBS
phosphate-buffered saline
In situ hybridization
CNS
central nervous system
Serotonergic
SERT
serotonin transporter
SPF
specific pathogen free
cDNA
complementary DNA
03 medical and health sciences
3D
3-dimensional
Free fatty acid receptor 2
Enterochromaffin Cells
Animals
Germ-Free Life
Humans
MRS
de Man
Rogosa and Sharpe
lcsh:RC799-869
Short-Chain Fatty Acids (SCFAs)
ENS
enteric nervous system
Host Microbial Interactions
Hepatology
Probiotics
Free Fatty Acid Receptor (FFAR)2
ISH
in situ hybridization
ACN
acetonitrile
biology.organism_classification
Molecular biology
Gastrointestinal Microbiome
030104 developmental biology
Receptors
Serotonin
2D
2-dimensional
Enteroids
biology.protein
Tph-1
tryptophan hydroxylase-1
lcsh:Diseases of the digestive system. Gastroenterology
Bifidobacterium
LC-MS/MS
liquid chromatography with tandem mass spectrometry
5-HT
5-hydroxytryptamine (serotonin)
GABA
γ-aminobutyric acid
Zdroj: Cellular and Molecular Gastroenterology and Hepatology, Vol 11, Iss 1, Pp 221-248 (2021)
Cellular and Molecular Gastroenterology and Hepatology
ISSN: 2352-345X
DOI: 10.1016/j.jcmgh.2020.08.002
Popis: Background & Aims The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. Methods Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT–receptor expression in the brain, and 5-HT–receptor–dependent behavior was evaluated using the marble burying test. Results B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium–secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT–receptor 2a in B dentium–treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT–receptor 2a. Conclusions These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.
Graphical abstract
Databáze: OpenAIRE
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