Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis.
Adult
Brain Mapping
/ methods
Case-Control Studies
Clostridiaceae
/ isolation & purification
Feces
Female
Gastrointestinal Microbiome
Humans
Irritable Bowel Syndrome
/ microbiology
Male
Prospective Studies
RNA, Ribosomal, 16S
/ genetics
Sensorimotor Cortex
/ physiopathology
Sequence Analysis, DNA
Somatosensory Cortex
/ physiopathology
Sweden
Young Adult
Bacteria
Brain imaging
Brain–gut axis
Central nervous system
Microbiome
Journal
Microbiome
ISSN: 2049-2618
Titre abrégé: Microbiome
Pays: England
ID NLM: 101615147
Informations de publication
Date de publication:
21 03 2019
21 03 2019
Historique:
received:
01
10
2018
accepted:
07
03
2019
entrez:
23
3
2019
pubmed:
23
3
2019
medline:
14
6
2019
Statut:
epublish
Résumé
Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.
Sections du résumé
BACKGROUND AND AIMS
Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function.
METHODS
We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function.
RESULTS
We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks.
CONCLUSIONS
In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.
Identifiants
pubmed: 30898151
doi: 10.1186/s40168-019-0656-z
pii: 10.1186/s40168-019-0656-z
pmc: PMC6429755
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
45Subventions
Organisme : NIMH NIH HHS
ID : F31 MH090749
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007180
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK096606
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK048351
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK041301
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD076756
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD086737
Pays : United States
Organisme : NIDDK NIH HHS
ID : P50 DK064539
Pays : United States
Références
Neuroimage. 2008 May 1;40(4):1765-71
pubmed: 18329293
Nat Rev Neurosci. 2009 Mar;10(3):186-98
pubmed: 19190637
Cell. 2015 Apr 9;161(2):264-76
pubmed: 25860609
Neurogastroenterol Motil. 2005 Dec;17(6):810-20
pubmed: 16336496
Pain. 2015 Aug;156(8):1545-54
pubmed: 25906347
Pain. 2002 Sep;99(1-2):313-21
pubmed: 12237210
Am J Gastroenterol. 2013 May;108(5):786-95
pubmed: 23588235
Gastroenterology. 2007 Oct;133(4):1113-23
pubmed: 17919487
Gut. 2018 Feb;67(2):255-262
pubmed: 28104632
Nutrients. 2017 Aug 26;9(9):
pubmed: 28846594
Pain. 2006 Dec 15;126(1-3):79-90
pubmed: 16846694
Nat Rev Gastroenterol Hepatol. 2013 Aug;10(8):473-86
pubmed: 23797870
Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):497-505
pubmed: 24751910
Neuroimage. 2012 Apr 2;60(2):1340-51
pubmed: 22305988
Am J Gastroenterol. 2012 May;107(5):754-60
pubmed: 22334251
Neuroimage Clin. 2017 Jun 02;15:449-457
pubmed: 28649489
Gut. 2012 Jul;61(7):997-1006
pubmed: 22180058
BMC Gastroenterol. 2009 Dec 17;9:95
pubmed: 20015409
Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209
pubmed: 25830558
Pain. 2015 Apr;156 Suppl 1:S50-63
pubmed: 25789437
J Neurosci. 2014 Nov 12;34(46):15490-6
pubmed: 25392516
Gut. 2003 May;52(5):663-70
pubmed: 12692050
PLoS One. 2018 Aug 6;13(8):e0201772
pubmed: 30080865
Brain Res. 1998 Nov 23;812(1-2):283-8
pubmed: 9813370
Neurogastroenterol Motil. 2016 Jan;28(1):127-38
pubmed: 26526698
Gastroenterology. 2014 Jan;146(1):67-75.e5
pubmed: 24076059
Curr Gastroenterol Rep. 2013 May;15(5):323
pubmed: 23580243
Brain Connect. 2012;2(3):125-41
pubmed: 22642651
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):10020-5
pubmed: 26216985
Gastroenterology. 2014 May;146(6):1500-12
pubmed: 24583088
Neurogastroenterol Motil. 2007 Sep;19(9):724-31
pubmed: 17539895
Clin Chim Acta. 2009 May;403(1-2):47-55
pubmed: 19361459
Appl Environ Microbiol. 1997 Jul;63(7):2802-13
pubmed: 9212428
Neurogastroenterol Motil. 2009 Jun;21(6):579-96
pubmed: 19646070
Neuroimage. 2010 Sep;52(3):1059-69
pubmed: 19819337
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7705-9
pubmed: 10393884
Pain. 2013 Sep;154(9):1528-41
pubmed: 23721972
Gastroenterology. 2006 Apr;130(5):1480-91
pubmed: 16678561
Clin Gastroenterol Hepatol. 2015 Jul;13(7):1371-1374.e3
pubmed: 25638586
Gastroenterology. 2006 Jan;130(1):34-43
pubmed: 16401466
Anesthesiology. 2005 Oct;103(4):821-7
pubmed: 16192775
Aliment Pharmacol Ther. 1997 Apr;11(2):395-402
pubmed: 9146781
Gastroenterology. 2017 Jan;152(1):111-123.e8
pubmed: 27725146
Gastroenterology. 2011 Jan;140(1):91-100
pubmed: 20696168
Neuroimage. 2012 Aug 15;62(2):881-6
pubmed: 21964480
Appl Environ Microbiol. 2004 Dec;70(12):7220-8
pubmed: 15574920
Cell Mol Gastroenterol Hepatol. 2018 Apr 12;6(2):133-148
pubmed: 30023410
Microbiome. 2017 May 1;5(1):49
pubmed: 28457228
Nat Rev Gastroenterol Hepatol. 2015 Oct;12(10):592-605
pubmed: 26303675