Brain identification of IBS patients based on GBDT and multiple imaging techniques.

The brain biomarker of irritable bowel syndrome (IBS) patients is still lacking. The study aims to explore a new technology studying the brain alterations of IBS patients based on multi-source brain data. In the study, a decision-level fusion method based on gradient boosting decision tree (GBDT) was proposed. Next, 100 healthy subjects were used to validate the effectiveness of the method. Finally, the identification of brain alterations and the pain evaluation in IBS patients were carried out by the fusion method based on the resting-state fMRI and DWI for 46 patients and 46 controls selected randomly from 100 healthy subjects. The results showed that the method can achieve good classification between IBS patients and controls (accuracy = 95%) and pain evaluation of IBS patients (mean absolute error = 0.1977). Moreover, both the gain-based and the permutation-based evaluation instead of statistical analysis showed that left cingulum bundle contributed most significantly to the classification, and right precuneus contributed most significantly to the evaluation of abdominal pain intensity in the IBS patients. The differences seem to suggest a probable but unexplored separation about the central regions between the identification and progression of IBS. This finding may provide one new thought and technology for brain alteration related to IBS.

Irritable Bowel Syndrome Is Associated With Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses.

BACKGROUND: Irritable bowel syndrome (IBS) interacts with psychopathology in a complex way; however, little is known about the underlying brain, biochemical, and genetic mechanisms. METHODS: To clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of IBS, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information. Multistage linked analyses were conducted, including phenome-wide association analysis, polygenic risk score calculation, and 2-sample Mendelian randomization analysis. RESULTS: The phenome-wide association analysis showed that IBS was linked to brain health problems, including anxiety and depression, and poor cognitive performance. Significantly lower brain volumes associated with more severe IBS were found in key areas related to emotional regulation and higher-order cognition, including the medial orbitofrontal cortex/ventromedial prefrontal cortex, anterior insula, anterior and mid-cingulate cortices, dorsolateral prefrontal cortex, and hippocampus. Higher triglycerides, lower high-intensity lipoprotein, and lower platelets were also related (p < 1 × 10-10) to more severe IBS. Finally, Mendelian randomization analyses demonstrated potential causal relationships between IBS and brain health and indicated possible mediating effects of dyslipidemia and inflammation. CONCLUSIONS: For the first time, this study provides a comprehensive understanding of the relationship between IBS and brain health phenotypes, integrating perspectives from neuroimaging, behavioral performance, biochemical factors, and genetics, which is of great significance for clinical applications to potentially address brain health impairments in patients with IBS.

Evaluation of gallbladder contractility and Doppler findings in patients with irritable bowel syndrome; a case-control study.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder causing abdominal pain, altered bowel habits and bloating without structural issues. Gallbladder dysfunction may be linked to IBS due to disrupted cholecystokinin release. This study aims to assess gallbladder function and related hemodynamic parameters using Doppler ultrasound in IBS before and after meals. METHOD: In this case-control study, we investigated gallbladder function differences between constipation-predominant IBS (C-IBS) patients and healthy volunteers. Participants underwent ultrasonography to measure gallbladder parameters before and after consuming a predefined meal. Gallbladder volume, wall thickness and resistance index (RI) of cystic and superior mesenteric arteries (SMA) were assessed. Student t-test and paired t-test were used to compare case and control groups and pre- and post-meal data, respectively. RESULTS: A total of 34 people (18 C-IBS and 16 healthy control) were included. The mean (Standard deviation) of gallbladder fasting volume was measured 24.74 (8.85) and 29.73 (9.65) cubic millimeter for case and controls, respectively. Postprandial volume was 11.34 (5.66) and 16.9 (6.16) cubic millimeter for case and controls respectively. We observed a statistically significant difference in emptying fractions (EF) between groups (p value = 0.009). IBS patients had a smaller fasting SMA RI (p value = 0.016) but the fraction of change after meal was not significant (p value = 0.10). The cystic artery RI did not reach statistical significance between the fasting and post-meal values (p value = 0.067). CONCLUSION: IBS patients have a higher emptying fraction and lower change in SMA RI compared to healthy controls. Further studies with larger sample size, inclusion of patients with different coexisting conditions and subtypes of IBS and combining colon transit study with gallbladder ejection fraction evaluation can be used to further provide more meaning to this study.

Brain activity in response to food images in patients with irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are caused and exacerbated by consumption of fatty foods. However, no study has evaluated brain activity in response to food images in patients with disorders of gut-brain interaction (DGBI). This study aimed to compare food preference and brain activity when viewing food images between patients with DGBI and healthy controls. METHODS: FD and IBS were diagnosed using the ROME IV criteria. Food preference was assessed using a visual analog scale (VAS). Brain activity in the prefrontal cortex (PFC) in response to food images was investigated using functional near-infrared spectroscopy (fNIRS). RESULTS: Forty-one patients were enrolled, including 25 with DGBI. The mean VAS scores for all foods (controls vs. FD vs. IBS: 69.1 ± 3.3 vs. 54.8 ± 3.8 vs. 62.8 ± 3.7, p = 0.02), including fatty foods (78.1 ± 5.4 vs. 43.4 ± 6.3 vs. 64.7 ± 6.1, p < 0.01), were the lowest in patients with FD among all groups. Patients with FD had significantly higher brain activity in the left PFC than those with IBS and healthy controls (mean z-scores in controls vs. FD vs. IBS: - 0.077 ± 0.03 vs. 0.125 ± 0.04 vs. - 0.002 ± 0.03, p < 0.001). CONCLUSIONS: Patients with DGBI, particularly those with FD, disliked fatty foods. The brain activity in patients with DGBI differed from that in healthy controls. Increased activity in the PFC of patients with FD was confirmed.

Dopamine transporter binding in the brain is linked to irritable bowel syndrome in Parkinson's disease.

BACKGROUND: Gastrointestinal symptoms are common in Parkinson's disease (PD), but their neurophysiological correlates are not well understood. We recently reported that functional gastrointestinal symptoms were not associated with asymmetry per se but might be associated with lower left striatal dopamine transporter (DAT) binding. The purpose of this study was to further investigate if specific gastrointestinal symptoms associate with monoamine transporter changes in specific striatal or extrastriatal areas. METHODS: Ninety PD patients, who underwent DAT ¹2 3 I-FP-CIT SPECT imaging, were assessed using the MDS-Unified Parkinson's Disease Rating Scale part III, Rome III, and Wexner constipation score. DAT binding was calculated from striatal subregions using region-to-occipital cortex ratio. Voxel-wise analysis was used to assess the relationship between gastrointestinal symptoms and striatal DAT and extrastriatal serotonin transporter (SERT) binding. RESULTS: Irritable bowel syndrome (IBS) criteria were fulfilled in 17 patients and were linked to higher ¹2 3 I-FP-CIT binding in the right posterior putamen and adjacent areas as compared to patients without IBS. No other significant associations between gastrointestinal symptoms and DAT or SERT binding were found. CONCLUSIONS: These findings suggest that PD patients with IBS may have higher DAT binding in the right hemisphere. This finding implicates alterations of brain neurotransmitter physiology in the gastrointestinal symptoms of PD patients.

Ultrasonographic and Functional Features of Symptomatic Uncomplicated Diverticular Disease.

INTRODUCTION: To evaluate the ability of intestinal ultrasound (IUS) in discriminating symptomatic uncomplicated diverticular disease (SUDD) among patients with abdominal symptoms including irritable bowel syndrome (IBS). METHODS: This observational, prospective study included consecutive patients classified into the following categories: (i) SUDD; (ii) IBS; (iii) unclassifiable abdominal symptoms; and (iv) controls, including asymptomatic healthy subjects and diverticulosis. The IUS evaluation of the sigmoid: assessed the presence of diverticula, thickness of the muscularis propria, and IUS-evoked pain, namely the intensity of pain evoked by compression with the ultrasound probe on sigmoid colon compared with an area of the left lower abdominal quadrant without underlying sigmoid colon. RESULTS: We enrolled 40 patients with SUDD, 20 patients with IBS, 28 patients with unclassifiable abdominal symptoms, 10 healthy controls, and 20 patients with diverticulosis. Patients with SUDD displayed significantly ( P < 0.001) greater muscle thickness (2.25 ± 0.73 mm) compared with patients with IBS (1.66 ± 0.32 mm), patients with unclassifiable abdominal pain, and healthy subjects, but comparable with that of patients with diverticulosis (2.35 ± 0.71 mm). Patients with SUDD showed a greater (not significant) differential pain score than other patients. There was a significant correlation between the thickness of the muscularis propria and the differential pain score only for patients with SUDD ( r = 0.460; P : 0.01). Sigmoid diverticula were detected by colonoscopy in 40 patients (42.4%) and by IUS with a sensitivity of 96.0% and a specificity of 98.5%. DISCUSSION: IUS could represent a useful diagnostic tool for SUDD, potentially useful in characterizing the disease and appropriately address the therapeutic approach.

Sex-specific brain microstructural reorganization in irritable bowel syndrome.

ABSTRACT: Preliminary evidence suggests that there are sex differences in microstructural brain organization among individuals with irritable bowel syndrome (IBS). The aim of this study was to further investigate sex-dependent differences in brain microstructure and organization in a large sample of well-phenotyped participants with IBS compared with healthy controls. We hypothesized that female patients with IBS would show evidence for increased axonal strength and myelination within and between brain regions concerned with pain and sensory processing, when compared with males with IBS. We also hypothesized that female compared with male IBS subjects show greater levels of somatic awareness and sensory sensitivity consistent with multisystem sensory sensitivity. Diffusion tensor images and clinical assessments were obtained in 100 healthy controls (61 females) and 152 IBS (107 females) on a 3T Siemens Trio. Whole brain voxel-wise differences in fractional anisotropy, mean, radial and axial diffusivity, and track density as differences in somatic awareness and sensory sensitivity were assessed using the general linear model. Female compared with male IBS participants showed extensive microstructural alterations in sensorimotor, corticothalamic, and basal ganglia circuits involved in pain processing and integration of sensorimotor information. Together with the observed increases in symptom severity, somatic awareness, and sensory sensitivity, the findings support the hypotheses that the etiology and maintenance of symptoms in females with IBS may be driven by greater central sensitivity for multiple sensory stimuli.

Visible abdominal distension in functional gut disorders: Objective evaluation.

BACKGROUND: Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation). METHODS: A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35. KEY RESULTS: (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent). CONCLUSIONS AND INFERENCES: In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity.

Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC. DESIGN: Women with IBS (n = 75), MDD (n = 41) and their respective HC (n = 39 and n = 43) underwent structural brain MRI. IC subregion volumes were estimated using statistical parametric mapping software. General linear model approaches were applied to IC volumetric data and FDR-corrected partial correlation analyses assessed relations between GMV, GI symptoms and Glx concentrations. RESULTS: IBS patients had significantly smaller IC subregions than HC in both hemispheres but there was no significant difference between MDD compared with IBS and HC for any insular subregion. In IBS, the dorsal anterior insular volumes were negatively correlated with symptoms of nausea and pain, and the left ventral subregion showed a positive correlation with straining to defecate, while the posterior subregion volumes showed no relation to symptoms. In the anterior insula, concentration of Glx showed positive correlations with GMV bilaterally in HC and with GMV of the right anterior insula in IBS. CONCLUSION: As the interoceptive cortex, the insula shows substantial and disease-specific structural differences in patients with chronic interoceptive visceral pain. Particularly changes in the anterior proportions might be related to chronic exposure to or enhanced salience towards adverse interoceptive visceral signals and could be linked to biochemical changes, calling for further multimodal and longitudinal work.

Magnetic resonance imaging assessed enteric motility and luminal content analysis in patients with severe bloating and visible distension.

BACKGROUND: Gastrointestinal symptoms in functional gut disorders occur without any discernible structural gut abnormality. Preliminary observations on enteric MRI suggest possible abnormal content and motility of the terminal ileum (TI) in constipation-predominant IBS (IBS-C) with severe bloating, and in functional bloating and distension (FABD) patients. We investigated whether MRI can quantify differences in small bowel (SB) content and motility between patients and healthy controls (HCs). METHODS: 11 IBS-C (mean age 40 [21-52] years; 10 women) and 7 FABD (36 [21-56]; all women) patients with bloating and 20 HCs (28 [22-48]; 6 women) underwent enteric MRI, including dynamic motility and anatomical sequences. Three texture analysis (TA) parameters assessed the homogeneity of the luminal content, with ratios calculated between the TI and (1) the SB and (2) the ascending colon. Four TI motility metrics were derived. Ascending colon diameter (ACD) was measured. A comparison between HCs and patients was performed independently for: (1) three TA parameters, (2) four TI motility metrics, and (3) ACD. KEY RESULTS: Compared with HCs, patients had TI:colon ratios higher for TA contrast (p < 0.001), decreased TI motility (lower mean motility [p = 0.04], spatial motility variation [p = 0.03], and area of motile TI [p = 0.03]), and increased ACD (p = 0.001). CONCLUSIONS AND INFERENCES: IBS-C and FABD patients show reduced TI motility and differences in luminal content compared with HCs. This potentially indicates reflux of colonic contents or delayed clearance of the TI, which alongside increased ACD may contribute to symptoms of constipation and bloating.

Abnormal resting-state local spontaneous functional activity in irritable bowel syndrome patients: A meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The current understanding of the pathogenesis underlying IBS is still unclear. Numerous studies have reported local abnormal resting state spontaneous functional activity in IBS patients in widespread brain regions. However, the results have not yet yielded consistent conclusions. Thus, we investigated common spontaneous functional activity abnormalities in patients with IBS by conducting a voxel-based meta-analysis. METHODS: Up to December 2021, we performed a systematic search of IBS studies in five databases. These studies investigated the differences of resting state spontaneous brain activity between patients with IBS and healthy controls (HCs). The reference lists of included studies, relevant reviews and meta-analyses were investigated manually. Anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis. RESULTS: Twelve studies encompassing 335 patients with IBS and 327 HCs were included in this meta-analysis. The local brain activities of the left calcarine fissure and surrounding cortex, right postcentral gyrus, left postcentral gyrus, left cerebellum, left inferior temporal gyrus, and left inferior frontal gyrus of triangular part in IBS patients were significantly increased compared with HCs, while the brain activities of the left anterior cingulate and paracingulate gyrus, right middle frontal gyrus, right supramarginal gyrus, left middle frontal gyrus, left precuneus, right putamen and right insula were significantly decreased compared with HCs. CONCLUSION: The current study expands on a growing literature exploring resting state activity in IBS, which provides useful insights for understanding the underlying pathophysiology of nonorganic functional bowel disease and developing more targeted treatment and intervention strategies.

Small bowel water content assessed by MRI in health and disease: a collation of single-centre studies.

BACKGROUND: New developments in MRI have allowed the non-invasive, accurate measurement of the small bowel water content (SBWC). AIMS: To collate studies measuring SBWC following ingestion of a range of foods in both health and disease to provide data for adequately powering future studies in this area. METHODS: This collation brings together 29 studies including 954 participants (530 healthy, 54 diverticulosis, 255 IBS, 53 functional constipation, 12 cystic fibrosis, 15 Crohn's disease, 20 coeliac disease, 15 scleroderma) which have been carried out in a single centre using comparable study designs. RESULTS: Fasting SBWC (mean 82 [SD 65] mL) shows high variability with a small decline with advancing age (healthy volunteers only; individual patient data). Fasting values are increased in untreated coeliac disease (202 [290] mL, P = 0.004). Post-prandial SBWC shows less intra-individual variability than fasting values in healthy volunteers. SBWC is increased by eating, most markedly by high fat meals but also by fibre, both viscous and particulate. Indigestible residue accumulates in late post-prandial period but empties soon after ingestion of a high calorie meal which produces a significant drop (by 50 [52] mL) in healthy volunteers. The associated fall in SBWC is abnormal in people with cystic fibrosis (SBWC reduced by 10 [121] mL, P = 0.002) and in people with irritable bowel syndrome with diarrhoea (SBWC reduced by 17 [43] mL, P = 0.007). CONCLUSIONS: SBWC as assessed by MRI is a valuable biomarker indicating the balance of secretion and absorption in health and disease and the impact of treatments.

[Dynamic characteristics of brain networks in patients with irritable bowel syndrome based on functional magnetic resonance imaging].

The disorder of brain-gut interaction is an important cause of irritable bowel syndrome (IBS), but the dynamic characteristics of the brain remain unclear. Since there are many shortcomings for evaluating brain dynamic nature in the previous studies, we proposed a new method based on slope calculation by point-by-point analysis of the data from functional magnetic resonance imaging, and detected the abnormalities of brain dynamic changes in IBS patients. The results showed that compared with healthy subjects, there were dynamic changes in the brain for the IBS patients. After correction by false discovery rate (FDR), significant abnormalities were only found in two functional connections of the right posterior cingulate gyrus linked to left middle frontal gyrus, and the right posterior cingulate gyrus linked to left pallidus. The above results of the brain dynamic analysis were totally different from those of the brain static analysis of IBS patients. Our findings provide novel complementary information for illustrating the central nervous mechanism of IBS and may offer a new direction to explore central target for patients with IBS.

Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration.

OBJECTIVE: We aimed to identify differences in network properties of white matter microstructure between asymptomatic ulcerative colitis (UC) participants who had a history of chronic gut inflammation, healthy controls (HCs) and a disease control group without gut inflammation (irritable bowel syndrome; IBS). DESIGN: Diffusion weighted imaging was conducted in age and sex-matched participants with UC, IBS, and HCs (N = 74 each), together with measures of gastrointestinal and psychological symptom severity. Using streamline connectivity matrices and graph theory, we aimed to quantify group differences in brain network connectivity. Regions showing group connectivity differences were correlated with measures showing group behavioral and clinical differences. RESULTS: UC participants exhibited greater centrality in regions of the somatosensory network and default mode network, but lower centrality in the posterior insula and globus pallidus compared to HCs (q < 0.05). Hub analyses revealed compromised hubness of the pallidus in UC and IBS compared to HCs which was replaced by increased hubness of the postcentral sulcus. Surprisingly, few differences in network matrices between UC and IBS were identified. In UC, centrality measures in the secondary somatosensory cortex were associated with depression (q < 0.03), symptom related anxiety (q < 0.04), trait anxiety (q < 0.03), and symptom duration (q < 0.05). CONCLUSION: A history of UC is associated with neuroplastic changes in several brain networks, which are associated with symptoms of depression, trait and symptom-related anxiety, as well as symptom duration. When viewed together with the results from IBS subjects, these findings suggest that chronic gut inflammation as well as abdominal pain have a lasting impact on brain network organization, which may play a role in symptoms reported by UC patients, even when gut inflammation has subsided.

Intrinsic brain abnormalities of irritable bowel syndrome with diarrhea: a preliminary resting-state functional magnetic resonance imaging study.

BACKGROUND: The aim of the present study was to explore the brain active characteristics of patients with irritable bowel syndrome with diarrhea (IBS-D) using resting-state functional magnetic resonance imaging technology. METHODS: Thirteen IBS-D patients and fourteen healthy controls (HC) were enrolled. All subjects underwent head MRI examination during resting state. A voxel-based analysis of fractional amplitude of low frequency fluctuation (fALFF) maps between IBS-D and HC was performed using a two-sample t-test. The relationship between the fALFF values in abnormal brain regions and the scores of Symptom Severity Scale (IBS-SSS) were analyzed using Pearson correlation analysis. RESULTS: Compared with HC, IBS-D patients had lower fALFF values in the left medial superior frontal gyrus and higher fALFF values in the left hippocampus and right precuneus. There was a positive correlation between the duration scores of IBS-SSS and fALFF values in the right precuneus. CONCLUSION: The altered fALFF values in the medial superior frontal gyri, left hippocampus and right precuneus revealed changes of intrinsic neuronal activity, further revealing the abnormality of gut-brain axis of IBS-D.

Association between pain sensitivity and gray matter properties in the sensorimotor network in women with irritable bowel syndrome.

BACKGROUND: Enhanced perception of visceral stimuli is an important feature of Irritable Bowel Syndrome (IBS), but it is not known whether visceral sensitivity is associated with regional structural brain properties in IBS. METHODS: Structural brain magnetic resonance imaging data from 216 women with IBS and 138 healthy women were parcellated with FreeSurfer to define regional gray matter morphometry (volume, cortical thickness, surface area and mean curvature) in the sensorimotor network. General linear models were used to detect group differences between IBS and health. In a second set of 48 female IBS patients, pain threshold, pain intensity ratings during rectal balloon distension, and reported levels of abdominal pain and bloating were correlated with brain regions that showed differences between IBS and health in the first data set. KEY RESULTS: Several statistically significant differences between IBS patients and healthy controls were found, mainly higher gray matter volume and cortical thickness in primary somatosensory cortex, secondary somatosensory cortex, and subcortical regions, and lesser gray matter volume, surface area and cortical thickness in posterior insula and superior frontal gyrus. Pain intensity ratings during rectal distension were associated with left primary somatosensory cortical thickness, and pain threshold was associated with right nucleus accumbens volume. CONCLUSIONS AND INFERENCES: Regional gray matter differences in sensorimotor network are associated with visceral sensitivity and may represent neuroplastic changes in female IBS patients.

Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity.

Irritable bowel syndrome (IBS) is a symptom-based disorder of gut-brain interactions generating abdominal pain. It is also associated with a vulnerability to develop extraintestinal symptoms, with fatigue often reported as one of the most disturbing. Fatigue is related to brain function and inflammation in several disorders, however, the mechanisms of such relations in IBS remain elusive. This study aimed to elucidate fatigue and its association with a resting state network of mesocorticolimbic regions of known importance in fatigue, and to explore the possible role of circulating TNF-α levels in IBS and healthy controls (HC). Resting state functional magnetic resonance imaging (fMRI) was conducted in 88 IBS patients and 47 HC of similar age and gender to investigate functional connectivity between mesocorticolimbic regions. Further, fatigue impact on daily life and plasma levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), of known relevance to immune activation in IBS, were also measured. The selected mesocorticolimbic regions indeed formed a functionally connected network in all participants. The nucleus accumbens (NAc), in particular, exhibited functional connectivity to all other regions of interest. In IBS, fatigue impact on daily life was negatively correlated with the connectivity between NAc and dorsolateral prefrontal cortex bilaterally (left p = 0.019; right p = 0.038, corrected for multiple comparisons), while in HC, fatigue impact on daily life was positively correlated to the connectivity between the right NAc and anterior middle insula in both hemispheres (left p = 0.009; right p = 0.011). We found significantly higher levels of TNF-α in IBS patients compared to HC (p = 0.001) as well as a positive correlation between TNF-α and fatigue impact on daily life in IBS patients (rho = 0.25, p = 0.02) but not in HC (rho = -0.13, p = 0.37). There was no association between functional connectivity in the mesocorticolimbic network and plasma levels of TNF-α in either group In summary, this novel multimodal study provides the first evidence that the vulnerability to fatigue in IBS is associated with connectivity within a mesocorticolimbic network as well as immune activation. These findings warrant further investigation, both peripherally and potentially with measurements of central immune activation as well.

Dynamic characteristics of brain networks in patients with irritable bowel syndrome based on functional magnetic resonance imaging / 生理学报

The disorder of brain-gut interaction is an important cause of irritable bowel syndrome (IBS), but the dynamic characteristics of the brain remain unclear. Since there are many shortcomings for evaluating brain dynamic nature in the previous studies, we proposed a new method based on slope calculation by point-by-point analysis of the data from functional magnetic resonance imaging, and detected the abnormalities of brain dynamic changes in IBS patients. The results showed that compared with healthy subjects, there were dynamic changes in the brain for the IBS patients. After correction by false discovery rate (FDR), significant abnormalities were only found in two functional connections of the right posterior cingulate gyrus linked to left middle frontal gyrus, and the right posterior cingulate gyrus linked to left pallidus. The above results of the brain dynamic analysis were totally different from those of the brain static analysis of IBS patients. Our findings provide novel complementary information for illustrating the central nervous mechanism of IBS and may offer a new direction to explore central target for patients with IBS.

Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndrome.

Alterations in brain-gut-microbiome (BGM) interactions have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Here, we apply a systems biology approach, leveraging neuroimaging and fecal metabolite data, to characterize BGM interactions that are driving IBS pathophysiology. Fecal samples and resting state fMRI images were obtained from 138 female subjects (99 IBS, 39 healthy controls (HCs)). Partial least-squares discriminant analysis (PLS-DA) was conducted to explore group differences, and partial correlation analysis explored significantly changed metabolites and neuroimaging data. All correlational tests were performed controlling for age, body mass index, and diet; results are reported after FDR correction, with q < 0.05 as significant. Compared to HCs, IBS showed increased connectivity of the putamen with regions of the default mode and somatosensory networks. Metabolite pathways involved in nucleic acid and amino acid metabolism differentiated the two groups. Only a subset of metabolites, primarily amino acids, were associated with IBS-specific brain changes, including tryptophan, glutamate, and histidine. Histidine was the only metabolite positively associated with both IBS-specific alterations in brain connectivity. Our findings suggest a role for several amino acid metabolites in modulating brain function in IBS. These metabolites may alter brain connectivity directly, by crossing the blood-brain-barrier, or indirectly through peripheral mechanisms. This is the first study to integrate both neuroimaging and fecal metabolite data supporting the BGM model of IBS, building the foundation for future mechanistic studies on the influence of gut microbial metabolites on brain function in IBS.