Tripartite association network.

<p>Fig 2 displays the tripartite association network between indole metabolites, clinical and behavioral measures, and functional and anatomical connectivity of the amygdala-NAcc circuit and the amygdala-aINS circuit. All significant (p < .05) associations are included in this visualization. Functional brain connectivity of regions of interest is presented with the region of interest noted in a larger font, with the connectivity measure and lateralization indicated below in the form X_Y, where X indicates a connectivity measure (B, Betweenness centrality; S, Degree strength) and Y indicates lateralization (L, Left; R, Right). Abbreviations: aINS, anterior insula; ALSHorp, horizontal ramus of the anterior segment of the lateral sulcus (aINS); ALSVerp, vertical ramus of the anterior segment of the lateral sulcus (aINS); Amg, amygdala; ANX, Hospital anxiety and depression (HAD) scale anxiety score; BMI, Body mass index; IAA, Indoleacetic acid; NAcc, nucleus accumbens; ShoInG, short insular gyrus (aINS); YFAS, Yale food addiction scale score.</p

Amygdala-anterior insula associations.

<p>Amygdala-anterior insula associations.</p

Correlation of tryptophan metabolites with connectivity of extended central reward network in healthy subjects

<div><p>Objective</p><p>A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions play an important role in human health and disease, including hedonic food intake and obesity. We performed a tripartite network analysis based on graph theory to test the hypothesis that microbiota-derived fecal metabolites are associated with connectivity of key regions of the brain’s extended reward network and clinical measures related to obesity.</p><p>Methods</p><p>DTI and resting state fMRI imaging was obtained from 63 healthy subjects with and without elevated body mass index (BMI) (29 males and 34 females). Subjects submitted fecal samples, completed questionnaires to assess anxiety and food addiction, and BMI was recorded.</p><p>Results</p><p>The study results demonstrate associations between fecal microbiota-derived indole metabolites (indole, indoleacetic acid, and skatole) with measures of functional and anatomical connectivity of the amygdala, nucleus accumbens, and anterior insula, in addition to BMI, food addiction scores (YFAS) and anxiety symptom scores (HAD Anxiety).</p><p>Conclusions</p><p>The findings support the hypothesis that gut microbiota-derived indole metabolites may influence hedonic food intake and obesity by acting on the extended reward network, specifically the amygdala-nucleus accumbens circuit and the amygdala-anterior insula circuit. These cross sectional, data-driven results provide valuable information for future mechanistic studies.</p></div

Amygdala-nucleus accumbens associations.

<p>Amygdala-nucleus accumbens associations.</p

Regions of interest and associated regions.

<p>Fig 1 displays regions of interest (nucleus accumbens [orange], amygdala [green], and anterior insula [blue; includes short insular gyrus, anterior segment of the circular sulcus of the insula, horizontal ramus of the anterior segment of the lateral sulcus, and vertical ramus of the anterior segment of the lateral sulcus]) and the brain stem (pink).</p

Regional means, standard deviations and Cohen’s effect size differences between groups.

<p>Groups: Healthy Control (HC), Irritable bowel syndrome (IBS).</p><p>Regions: aINS: anterior insula; mINS: middle insula, pINS: posterior insula; sgACC: subgenual anterior cingulate cortex; pgACC: pregenual cingulate cortex; aMCC: anterior mid cingulate cortex; pMCC: posterior mid cingulate cortex.</p><p>M: mean, es: effect size.</p

Descriptive Demographic Data.

<p>Groups: Healthy Control (HC), Irritable bowel syndrome (IBS).</p

Clinical variables for IBS patients.

<p>Groups: Healthy Control (HC), Irritable bowel syndrome (IBS).</p

Differences in Cortical Thickness between Female IBS and Female HC.

<p>Upper: difference between female IBS and female controls from whole brain grey matter thickness analysis projected on average surfaces. T maps (uncorrected) were color coded: orange/red = thickening; blue/purple = thinning. Green = no change. Lower: FDR corrected p map from whole brain grey matter thickness analysis. Orange/red = female>male; blue/cyan = female</p

Correlation matrix between mean MD measurements and MAPP symptom scores in UCPPS patients, localized to ROIs identified as different between UCPPS and HCs on statistical parameter maps.

<p>Dendrograms on the left side of the correlation matrix show hierarchical clustering of ROIs based on the association between MD measurements and symptom scores. Images showing ROI localization are chosen for select associations. Up arrows within cells denote significantly positive correlations (<i>P<0</i>.<i>05</i>) and down arrows within cells denote significantly negative correlations (<i>P<0</i>.<i>05</i>). (Note the level of significance was not corrected for multiple comparisons in this exploratory analysis).</p