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

Abstract

Background and aimsEvidence 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.MethodsWe 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.ResultsWe 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0656-z) contains supplementary material, which is available to authorized users.

History of early life adversity is associated with increased food addiction and sex‐specific alterations in reward network connectivity in obesity

“…The results are described in terms of direct effects (nodes connected by an edge) or indirect effects (nodes that are connected to other regions via the edges of other nodes but that do not share an edge). The analysis presumes that associations present in one group, which are missing in another, not only differentiate the groups but also indicate potential clues to the functionality of the system; this approach has been used previously . Comparisons were made between all the brain networks representing each group in order to identify desease and sex effects: (1) the high BMI group versus the normal BMI group (disease effect) and (2) the women with high BMI group versus the men with high BMI group (sex effect).…”

Effect of gut microbiota from Henoch-Schönlein Purpura patients on acid-sensitive ion channel 3 expression and intestinal motility in Germ-free rats

“…Alterations to the intestinal microbiota could trigger or aggravate visceral hypersensitivity in functional gastrointestinal disorder diseases and affect gastrointestinal motility [19][20][21][22]. Studies have shown that intestinal bacteria may participate in the pathophysiological process of HSP, and the microbiota may be highly involved in the occurrence of abdominal pain in HSP patients [23].…”

Veränderungen der Darm-Gehirn-Achse beim Reizdarmsyndrom – Ein Update

“…Bei Patienten mit RDS wurden neben den genannten Veränderungen im Immunsystem auch Unterschiede bezüglich des Mikrobioms im Vergleich zu gesunden Kontrollen beobachtet [45] [46]. Eine systematische Analyse zeigte im Stuhl von RDS-Patienten vermehrt Firmicutes und Clostridia sowie weniger Bacteroidetes im Vergleich zu gesunden Kontrollen [46].…”

“…Eine systematische Analyse zeigte im Stuhl von RDS-Patienten vermehrt Firmicutes und Clostridia sowie weniger Bacteroidetes im Vergleich zu gesunden Kontrollen [46]. Die deutlichsten Veränderungen wurden bei Lachnospiraceae incertae sedis oder Clostridium XIVa gefunden [45]. Vorstudien konnten zeigen, dass gastrointestinale Mikrobiota Veränderungen der Serotonin-Konzentrationen hervorrufen können, was wiederum Veränderungen der gastrointestinalen Motilität bewirkt [47].…”

“…Vorstudien konnten zeigen, dass gastrointestinale Mikrobiota Veränderungen der Serotonin-Konzentrationen hervorrufen können, was wiederum Veränderungen der gastrointestinalen Motilität bewirkt [47]. Eine aktuelle Untersuchung untermauert die Hypothese des Einflusses der Mikrobiota auf die Darm-Gehirn-Achse, da Clostridium XIVa eine positive Assoziation mit der Konnektivität subkortikaler Regionen wie des Putamen oder des Thalamus aufweist [45]. Des Weiteren konnten morphometrische Unterschiede im Gehirn abhängig vom jeweiligen Mikrobiota-Profil gezeigt werden, was auf einen möglichen Einfluss der gastrointestinalen Mikrobiota bzw.…”