Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

Abstract

BackgroundPreclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS.MethodsBehavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions.ResultsUsing unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma.ConclusionsThe results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0260-z) contains supplementary material, which is available to authorized users.

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…Although two studies failed to find a relationship between overall microbiota composition and amygdala volume in IBS patients and healthy women, [95,123] another identified a particular bacterial phylum that was associated with microstructure of this region. [128] That is, abundance of Actinobacteria correlated with increased fractional anisotropy in the amygdala.…”

“…[51] Indeed, IBS is associated with altered microbiota composition, at least in a substantial subset of patients. [123,124] Furthermore, the microbiota has been causally implicated in IBS in two studies utilising fecal microbiota transplant. [125,126] By transferring the microbiota from IBS patients into healthy mice, characteristic symptoms of IBS gastrointestinal dysfunction can be induced, including accelerated gastrointestinal transit and increased intestinal permeability.…”

“…Morphology Enlarged volume, increases in dendritic length, branch points and spine density in mice [16] No correlation between microbiota composition and amygdala volume in healthy women or IBS patients [95,123] Actinobacteria correlated with enhanced microstructure (increased fractional anisotropy) [128] Activity and connectivity Dampened activity during emotional faces task, altered resting state connectivity with distributed network including hippocampus and thalamus [35] Microbiota profile associated with structural white-matter connectivity in healthy women and with functional connectivity in young children [95,129] Gene expression Specific mRNA expression: NGFI-A, BDNF decreased, NR2B decreased in CeA of mice [5,9] Whole genome sequencing: broad alterations suggestive of upregulation of neuronal activity, differential gene regulation in response to fear and social stimuli [36,101] (Stilling et al, unpublished observations) mRNA expression: Nr3c1, CRH-R1 decreased, BDNF increased in rats [94] Protein expression: BDNF decreased in mice [4] Lactobacillus rhamnosus (JB-1) decreased GABA B1b mRNA in BLA and CeA of mice [62] Broad dysregulation of miRNA in mice [37] www.advancedsciencenews.com www.bioessays-journal.com amygdala was altered for the probiotic-treated participants. Essentially, these data provide the first evidence of a clinical link between the microbiota and functional connectivity of the amygdala.…”

Influence of Early Life, Diet, and the Environment on the Microbiome

“…Factors linked to the pathogenesis of IBS includes a history of enteric infection, alteration in the gut-brain axis, changes in visceral sensitivity, and modifications in the gut microbiome. 44,121 Studies have linked early life stress and adverse events to microbial shifts that could potentially be the cause of visceral sensitivity and subsequent IBS development. 44,109,122 IBS patients generally had less Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii than healthy controls.…”

“…44,121 Studies have linked early life stress and adverse events to microbial shifts that could potentially be the cause of visceral sensitivity and subsequent IBS development. 44,109,122 IBS patients generally had less Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii than healthy controls. 114 While it is unclear which changes are necessary and/or sufficient, studies in germ-free mice transplanted with fecal microbes from IBS patients causes alterations in gut permeability, motility, visceral perception, and food processing that ultimately triggers IBS symptoms.…”