| 1. |
- Moraes Holst, Luiza, et al.
(author)
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Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
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Journal article (peer-reviewed)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
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| 2. |
- Uusijärvi, A., et al.
(author)
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Use of antibiotics in infancy and childhood and risk of recurrent abdominal pain-a Swedish birth cohort study
- 2014
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In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 26:6, s. 841-850
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Journal article (peer-reviewed)abstract
- Background: The etiology of recurrent abdominal pain of functional origin (AP) is largely unknown. Antibiotic treatment influences the intestinal microbiota, and a few studies have indicated an increased risk of AP in adults after antibiotic treatment. Corresponding data in children are lacking. The aim of this study was to explore the association between antibiotic treatment during childhood and AP at 12years.Methods: Two thousand seven hundred and thirty-two children from a Swedish, population-based birth cohort. Parents reported antibiotic use for the children between birth and 2years. Antibiotic use between 9 and 12years was collected from the Swedish Prescribed Drug Register. The children answered questionnaires regarding AP at age 12. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for AP at 12years as a function of antibiotic use.Key Results: Antibiotic treatment between 9 and 12years was not associated with AP at 12. Children who had received 3 courses, or broad-spectrum antibiotics between 9 and 12years had an increased risk of AP at 12, but these associations failed to reach statistical significance. Antibiotic treatment during both the first and the second year of life increased the risk of AP in girls at 12 (OR 1.65; 95% CI: 1.09-2.49), but not in boys or the whole cohort.Conclusions & Inferences: Antibiotic treatment does not seem to be a major risk factor for AP at 12years. However, we cannot exclude that repeated courses, especially to infant girls, or use of broad-spectrum antibiotics between 9 and 12years may be associated with an increased risk of AP.
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| 3. |
- Polster, Annikka, et al.
(author)
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Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms
- 2018
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:7
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Journal article (peer-reviewed)abstract
- BackgroundDisturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms. MethodsHeart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24-hour period). Frequency (5minutes, supine, standing) and time domains (24hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS-DA)). Key ResultsWe analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P<.01). A subset of patients (n=30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS-DA; these patients reported more severe symptoms of frequent (P<.05) and loose stools (P=.03), as well as urgency (P=.01). Conclusions and InferencesAltered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.
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| 4. |
- Brock, C., et al.
(author)
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Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis
- 2013
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3698-3705
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Journal article (peer-reviewed)abstract
- OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.RESULTSDiabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P 0.001), and showed diminished amplitude of the N2-P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P 0.001).CONCLUSIONSThis study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.
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| 5. |
- Frokjaer, J. B., et al.
(author)
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Macrostructural Brain Changes in Patients with Longstanding Type 1 Diabetes Mellitus - a Cortical Thickness Analysis Study
- 2013
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In: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 121:6, s. 354-360
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Longstanding diabetes mellitus (DM) is associated with the risk of complications Methods: 15 patients with longstanding (average 24.6 years) type 1 DM and 20 healthy controls were Results: No differences between patients and controls were found in regard to number of white matter Conclusions: Patients with longstanding type 1 diabetes showed cortical thinning involving sensory
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| 6. |
- Klingberg, Eva, et al.
(author)
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A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin
- 2019
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Journal article (peer-reviewed)abstract
- Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map (TM) Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1-5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (<= 50 mg/kg, n = 57) and increased (>= 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI >= 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS.
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| 7. |
- Lelic, D, et al.
(author)
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The brain networks encoding visceral sensation in patients with gastrointestinal symptoms due to diabetic neuropathy.
- 2014
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 26:1, s. 46-58
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Journal article (peer-reviewed)abstract
- Increasing evidence points to association between long-term diabetes mellitus and abnormal brain processing. The aim of this study was to investigate central changes due to electrical stimulation in esophagus in patients with upper gastrointestinal (GI) symptoms due to diabetic neuropathy.
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| 8. |
- Whitehead, W. E., et al.
(author)
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Biomarkers to distinguish functional constipation from irritable bowel syndrome with constipation
- 2016
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:6, s. 783-792
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Journal article (peer-reviewed)abstract
- Treatments for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum. © 2016 John Wiley & Sons Ltd.
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| 9. |
- Bennet, Sean, et al.
(author)
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Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
- 2016
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 111:8, s. 1165-1176
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.
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| 10. |
- Bennet, Sean M. P., et al.
(author)
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Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs
- 2018
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:5, s. 872-881
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Journal article (peer-reviewed)abstract
- Objective The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response. Design Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available. Results Responders (reduced IBS-SSS by >= 50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption. Conclusions A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles.
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