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BACKGROUND: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. METHODS: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. RESULTS: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058). CONCLUSION: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.
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Doença Celíaca , Colite Colagenosa , Colite Linfocítica , Colite Microscópica , Síndrome do Intestino Irritável , Humanos , Feminino , Colite Linfocítica/epidemiologia , Colite Linfocítica/complicações , Colite Linfocítica/patologia , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/complicações , Estudos Retrospectivos , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Colite Microscópica/epidemiologia , Colite Microscópica/patologia , Colite Colagenosa/epidemiologia , Colite Colagenosa/complicações , Colite Colagenosa/patologiaRESUMO
BACKGROUND: Medical student master's theses are often carried out as research projects, and some are published as research papers in journals. We investigated the percentage of master's theses conducted by 5th -year students at the Medical Degree Program at Lund University, Sweden, that subsequently served as the basis for research publications. In addition, we explored both student and supervisor experiences with the publishing process. METHODS: A cohort of four semesters of student data covering the period from 2019 to 2020 (n = 446) was searched in PubMed, Embase and the Web of Science to assess whether they had been published as research papers. Surveys were sent to students (n = 121) and supervisors (n = 77) to explore their experiences with the publishing process. RESULTS: We found that 33% (149 of 446) of the students in the 2019-2020 cohort subsequently published their theses, and 50% of these students were listed as first authors. Most students published original research. Students (n = 21) and supervisors (n = 44) reported that the publishing process was time-consuming and that students needed multilevel support from supervisors to achieve successful publication. The publishing process was reported by 79% of the students to have led to additional learning. Most of the papers (126 of 149, 85%) had a clinical or patient-oriented focus. CONCLUSION: A high percentage of the student publications in which students are listed as first authors require engagement from both students and supervisors. Supervisors play an essential role in supporting students in a successful publication process. Most of the published papers were either clinical or patient-oriented research.
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Estudantes de Medicina , Humanos , Editoração , Faculdades de Medicina , Aprendizagem , PesquisadoresRESUMO
Pancreas-derived islet amyloid polypeptide (IAPP) aggregates and deposits in the pancreas and periphery of Type 2 Diabetes (T2D) patients, contributing to diabetic complications. The excess IAPP can be removed by autoantibodies, and increased levels of immunoglobulin (Ig) G against IAPP have been reported in T2D patients. However, whether other Ig classes are also affected and if the levels can be managed is less known. This pre-post study examines IgA levels against IAPP oligomers (IAPPO-IgA) in T2D patients and assesses the impact of the Okinawa-based Nordic (O-BN) diet-a low-carbohydrate, high-fiber diet-on these levels after following the diet for 3 months. IAPP, IAPPO-IgA, and total IgA levels were measured in plasma and fecal samples from n = 30 T2D patients collected at baseline, after 3 months of diet, and after additional 4 months of unrestricted diets (a clinical follow-up). The IAPP and IAPPO-IgA levels were significantly lower after 3 months, with the latter also being significantly reduced at the clinical follow-up. The reduction in plasma IAPP and IAPPO-IgA levels correlated with reductions in plasma levels of metabolic and inflammatory markers. Hence, following the O-BN diet for at least 3 months is sufficient to reduce circulating IAPP and IAPPO-IgA levels, which may be principal in managing T2D.
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Diabetes Mellitus Tipo 2 , Imunoglobulina A , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Imunoglobulina A/sangue , Imunoglobulina A/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Japão , AdultoRESUMO
INTRODUCTION: Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and pathophyisology. Increased knowledge of mechanisms may provide insight into enteric neuropathy with gastrointestinal dysmotility. The aim of the present systematic review was to identify mechanisms behind diffuse idiopathic peripheral neuropathies in humans. METHODS: Searches were performed in PubMed, Embase, and Web of Science. Human original and review articles, written in English, describing mechanisms behind diffuse peripheral neuropathy verified by objective examinations were intended to be studied. Articles that described animal models, well-described hereditary diseases, drug-induced neuropathy, pain syndromes, malnutrition, and local neuropathy were excluded. RESULTS: In total, 4712 articles were identified. After scrutinizing titles and abstracts, 633 remained and were studied in full text. After the removal of articles not fulfilling inclusion or exclusion criteria, 52 were finally included in this review. The most frequently described neuropathy was diabetic neuropathy, with a wide range of mechanisms involving mitochondrial dysfunction such as oxidative stress and inflammation. Microvascular changes in diabetes and vasculitis lead to ischemia and secondary oxidative stress with inflammation. Structural changes in neurons and glial cells are observed, with abnormalities in different neurotrophic factors. Neuropathy induced by autoantibodies or immunological mechanisms is described in infectious and systemic inflammatory diseases. Several ion channels may be involved in painful neuropathy. No study identified why some patients mainly develop large fiber neuropathy and others small fiber neuropathy. CONCLUSION: Metabolic and immunological factors and channelopathy may be considered in diffuse idiopathic peripheral neuropathy.
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Neuropatias Diabéticas , Dor , Humanos , InflamaçãoRESUMO
BACKGROUND: Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. METHOD: The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups. RESULTS: Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06-3.26; p = 0.029), as well as with age 50-59 years (OR:6.92; 95%CI:1.97-24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56-25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08-5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19-7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14-4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02-3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14-2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98-1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03-1.89; p = 0.033) and inversely with age 50-59 years (OR:0.58; 95%CI:0.38-0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants. CONCLUSION: There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.
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Endometriose , Gastroenteropatias , Síndrome do Intestino Irritável , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Endometriose/complicações , Endometriose/epidemiologia , Gastroenteropatias/complicações , Fatores de Risco , Fumar/epidemiologia , Inquéritos e QuestionáriosRESUMO
Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
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Ácidos e Sais Biliares/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The prevalence of functional gastrointestinal (FGI) symptoms and irritable bowel syndrome (IBS) is high in the society, but the etiology is mainly unknown. This population-based, cross-sectional study aimed to examine the associations between self-reported IBS or gastrointestinal (GI) symptoms within the past 2 weeks and concomitant diseases, drug consumption and family history of diseases. MATERIAL AND METHODS: Participants from the Malmö Offspring Study (MOS) answered a questionnaire about lifestyle habits, medical history and GI symptoms. Associations between self-reported IBS or GI symptoms and other diseases, drugs, and family history of diseases were calculated by logistic regression, adjusted for false discovery rate (FDR; q < 0.05). RESULTS: Of 2648 included patients, 316 had IBS and 459 had GI symptoms. There was an association between IBS and asthma (OR: 1.66; 95% confidence interval [CI]: 1.19-2.32; q = 0.018), and between IBS and using of prescription (OR: 1.44; 95% CI: 1.10-1.89; q = 0.028) and nonprescription drugs (OR: 1.92; 95% CI: 1.43-2.59; q < 0.001), specifically adrenergic beta-antagonists, antihistamines and hypnotics. Regarding family history, GI disease in the family (OR: 2.44; 95% CI: 1.78-3.35; q < 0.001) and the subgroups celiac disease, gastric ulcer, functional dyspepsia, IBS and reflux, as well as prostate cancer were associated with IBS, while GI diseases (OR: 2.56; 95% CI: 1.89-3.46; q < 0.001), joint diseases (OR: 1.61; 95% CI: 1.19-2.16; q = 0.009), and myocardial infarction (OR: 1.48; 95% CI: 1.09-2.99; q = 0.043) were associated with GI symptoms. Abdominal pain was the specific symptom with strongest associations. CONCLUSIONS: IBS and GI symptoms were mainly associated with GI diseases in the family and drug consumption. To take a family and drug history is pertinent to all clinical history taking, irrespective of the symptomatology.
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BACKGROUND AND AIM: Poor food habits with insufficient intake of micronutrients have been described in irritable bowel syndrome (IBS), which could be of importance for development of gastrointestinal and extraintestinal symptoms. The study aims were to examine intake and plasma/serum levels of micronutrients in IBS and whether these factors were associated with symptoms and restrictions and to study the effects of a starch- and sucrose-reduced diet (SSRD). METHODS: One hundred five patients with IBS or functional gastrointestinal disorder (FGID) according to Rome IV criteria were included to SSRD/controls for 4 weeks. Patients completed a study questionnaire about lifestyle habits, medical health, IBS-symptom severity score (IBS-SSS), visual analog scale for IBS (VAS-IBS), and diary books before and after study start. Plasma/serum levels of micronutrients were analyzed at baseline. RESULTS: Intake of micronutrients at baseline was lower than recommended according to national guidelines. Gastrointestinal symptoms were inversely associated with intake and plasma levels of iron. Extraintestinal symptoms and fatigue inversely associated with intake of vitamin B6, phosphorus, magnesium, and iodine, as was plasma levels of iron, and positively associated with plasma iron-binding capacity. Fatigue was also inversely associated with calcium, iron, and zinc intakes. Plasma ferritin was lower in participants on restrictions. SSRD increased the intake of several vitamins, selenium, and fat, whereas sodium intake was decreased, with markedly reduced symptoms. CONCLUSION: Irritable bowel syndrome patients had low intake of micronutrients at baseline, which associated inversely with total IBS-SSS, extraintestinal IBS-SSS, and fatigue. SSRD increased the intake of several micronutrients, which correlated weakly with symptom improvement.
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Síndrome do Intestino Irritável , Fadiga/complicações , Humanos , Ferro , Síndrome do Intestino Irritável/diagnóstico , Minerais , Vitamina A , Vitamina K , VitaminasRESUMO
BACKGROUND: Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease. METHODS: Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed. RESULTS: Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins. CONCLUSION: The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.
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Endometriose , Estudo de Associação Genômica Ampla , Endometriose/diagnóstico , Endometriose/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Fatores de RiscoRESUMO
Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML = 0.87, 95% CI: 0.76-0.99, HR-CEL = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1 = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML = 1.28, 95% CI: 1.05-1.56, HR-CEL = 1.17; 95% CI: 0.96-1.40, HR-MH-G1 = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.
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Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metabolômica/métodos , Idoso , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida , Comportamento Alimentar , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Espectrometria de Massas , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated examinations such as full-thickness bowel biopsy. We hypothesized that knowledge about simultaneous occurrence of different types of neuropathy would lead to faster recognition and diagnosis of autonomic/enteric neuropathy. The aim of the present systematic review was to increase the awareness of disease groups causing autonomic and enteric neuropathy along with sensorimotor neuropathy. METHODS: A systematic search strategy was used in PubMed, Embase and Web of Science. First, 4978 articles were identified. Review of titles/abstracts rendered exclusion of animal studies, articles not written in English or full-length, case reports, conference abstracts and duplicates until 357 articles remained. The full-length evaluation resulted in 35 studies (27 non-systematic reviews) which described objectively verified peripheral autonomic, enteric and sensorimotor neuropathy within the same disease. RESULTS: Diabetes is the most common disease in society rendering generalized peripheral neuropathy. Accumulation of tissue deposits in amyloidosis, Lewy body disorders and sarcoidosis lead to widespread peripheral neuropathy. Several autoimmune disorders such as systemic sclerosis and primary Sjögren's syndrome present themselves with neuropathy. Paraneoplastic neuropathy may appear prior to symptoms from the malignancy. Both the infection per se, as well as the autoimmune response to the infection, i.e., Guillain-Barré syndrome, may lead to widespread peripheral neuropathy. Hereditary disorders with disturbed metabolism lead to intermittent attacks of neuropathy. CONCLUSIONS: The major causes of generalized peripheral neuropathy are diabetes, diseases with tissue deposits, autoimmunity, infections, malignancy and metabolic diseases.
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Doenças Autoimunes , Síndrome de Guillain-Barré , Neoplasias , Doenças do Sistema Nervoso , Doenças do Sistema Nervoso Periférico , Animais , Síndrome de Guillain-Barré/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologiaRESUMO
As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
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Dieta , Estilo de Vida , Síndrome Metabólica , Microbiota , Adolescente , Adulto , Idoso , Fatores de Risco Cardiometabólico , Doença Crônica , Exercício Físico , Família , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Suécia , Adulto JovemRESUMO
BACKGROUND AND AIM: Altered gut microbiota have been suggested as part of an etiology of irritable bowel syndrome (IBS), but studies have shown contrasting results. Our aim was to examine gut microbiota composition in a large population-based cohort, with respect to presence and severity of bowel symptoms. METHODS: The study cohort consisted of 1988 participants of the Malmö Offspring Study (mean age 40 years, 53% women). From a questionnaire, 19% reported having bowel symptoms the last 2 weeks and 15% reported having IBS. Bowel symptoms were assessed by a validated set of questions with visual analog scales. Gut microbiota was assessed by 16S rRNA gene sequencing (300 bp*2 in V1-V3 region) from fecal samples. The association between abundance of bacteria at genus level and bowel symptoms was calculated by logistic regression or general linear model, adjusted for false discovery rate (q < 0.05). RESULTS: Self-reported bowel symptoms (P = 0.003) and IBS (P = 0.031) were associated with difference in overall gut microbiota composition (beta-diversity). Additionally, bowel symptoms and IBS were associated with increased abundance of Blautia, and bowel symptoms also with a genus in the SHA98 order and Butyricimonas. Pain was associated with increased abundance of Fusobacterium. Diarrhea was associated positively with [Prevotella] and Blautia and negatively with a genus in the SHA98 order and a genus in the Christensenellaceae family. CONCLUSION: Self-reported bowel symptoms are associated with differences in overall gut microbiota composition and abundancy of a few specific bacteria at genus level in a population-based cohort. Diarrhea is the individual symptom with most associations.
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Microbioma Gastrointestinal , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Autorrelato , Dor Abdominal/etiologia , Dor Abdominal/microbiologia , Adulto , Bacteroidetes , Clostridiales , Estudos de Coortes , Diarreia/etiologia , Diarreia/microbiologia , Fezes/microbiologia , Feminino , Fusobacterium , Humanos , Síndrome do Intestino Irritável/complicações , Masculino , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. MATERIAL AND METHODS: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. RESULTS: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. CONCLUSIONS: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.
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Epiderme , Fibras Nervosas , Biópsia , Derme , Humanos , Projetos Piloto , Pele/diagnóstico por imagemRESUMO
BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with ulcerative colitis (UC), even when the disease is in remission, possibly due to abnormalities in GI motility. Small bowel motility can be assessed globally and in specific intestinal regions during magnetic resonance enterography (MRE) using a displacement mapping technique. PURPOSE: To investigate whether small bowel motility in MRE differs between patients with UC and controls, and if altered motility correlates with GI symptoms. MATERIAL AND METHODS: In 2016-2018, patients who were admitted for MRE, regardless of clinical indication, were consecutively invited to the study. Healthy volunteers were recruited. The participants completed a questionnaire regarding GI symptoms and relevant clinical data were reviewed in the medical records. The dynamic imaging series obtained during MRE were sent for motility mapping and a motility index (MI) was calculated in jejunum, ileum and terminal ileum in all participants. RESULTS: In total, 224 patients and healthy volunteers were enrolled in the study. Fifteen were diagnosed with UC and 22 were considered healthy controls. In UC, the prevalence of GI symptoms was higher than in controls (P < 0.001), both in remission and in active disease. There was no correlation between GI symptoms and small bowel motility in UC. Jejunal motility was lower in UC than in controls (P = 0.049). CONCLUSION: Jejunal motility is decreased in UC compared with healthy controls, but there is no relationship between small bowel motility and GI symptoms in UC.
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Colite Ulcerativa/complicações , Colite Ulcerativa/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Íleo/fisiopatologia , Jejuno/fisiopatologia , Adulto , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Íleo/diagnóstico por imagem , Jejuno/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
OBJECTIVE: The studies of early life factors and development of functional bowel diseases show inconsistent results. We therefore examined associations between certain early life factors and functional bowel symptoms in adulthood. DESIGN: Population-based cross-sectional study. SETTING: Weight and height were measured and questionnaires were completed at the time point of enrollment in MOS. SUBJECTS: 1013 participants in the Malmö Offspring Study (MOS) without organic bowel disease with data available from the Swedish Medical Birth Registry. MAIN OUTCOME MEASURES: Associations were calculated between gestational age, birth weight, small-for-gestational-age and Apgar score from the Birth Registry, and symptoms according to the visual analog scale for irritable bowel syndrome (VAS-IBS) (abdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea, and symptoms' influence on daily life) or self-reported IBS using logistic regression. RESULTS: In all, 253 (25.0%) participants reported bowel symptoms during the past 2 weeks and 179 (17.7%) self-reported IBS; conditions which were strongly associated (p < 0.001). Female sex and chronic stress were two independent factors more common among participants with bowel symptoms compared with asymptomatic participants (p < 0.001). Early life factors were not associated with presence of overall bowel symptoms (p = 0.080), any specific bowel symptoms or self-reported IBS. Lower birth weight (p = 0.038) and being born small for gestational age (p = 0.043) were associated with severe influence of intestinal symptoms on daily life in adulthood. CONCLUSIONS: Lower birth weight and small for gestational age are not associated with the presence of overall bowel symptoms but with more pronounced influence of such symptoms on daily adult life.Key pointsLower gestational age tended to be associated with functional bowel symptoms in adulthood.Lower birth weight and being small for gestational age are associated with increased negative influences of symptoms on daily life in adulthood.Patients born preterm or with low birth weights may be at increased risk to develop functional bowel symptoms later in life.
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Síndrome do Intestino Irritável , Dor Abdominal/etiologia , Adulto , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Estudos Transversais , Diarreia/epidemiologia , Diarreia/etiologia , Feminino , Flatulência , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/etiologia , Inquéritos e QuestionáriosRESUMO
Telocytes (TCs) are recently described interstitial cells, present in almost all human organs. Among many other functions, TCs regulate gastrointestinal motility together with the interstitial cells of Cajal (ICCs). TCs and ICCs have close localization in the human myenteric plexus; however, the exact spatial relationship cannot be clearly examined by previously applied double immunofluorescence/confocal microscopy. Data on TCs and submucosal ganglia and their relationship to intestinal nerves are scarce. The aim of the study was to analyse the spatial relationship among these components in the normal human ileum and colon with double CD34/CD117 and CD34/S100 immunohistochemistry and high-resolution light microscopy. TCs were found to almost completely encompass both myenteric and submucosal ganglia in ileum and colon. An incomplete monolayer of ICCs was localized between the TCs and the longitudinal muscle cells in ileum, whereas only scattered ICCs were present on both surfaces of the colonic myenteric ganglia. TC-telopodes were observed within colonic myenteric ganglia. TCs, but no ICCs, were present within and around the interganglionic nerve fascicles, submucosal nerves and mesenterial nerves, but were only observed along small nerves intramuscularly. These anatomic differences probably reflect the various roles of TCs and ICCs in the bowel function.
Assuntos
Colo/anatomia & histologia , Sistema Nervoso Entérico/citologia , Íleo/anatomia & histologia , Células Intersticiais de Cajal/fisiologia , Telócitos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Colo/citologia , Colo/inervação , Feminino , Humanos , Íleo/citologia , Íleo/inervação , Masculino , Pessoa de Meia-Idade , Plexo Mientérico/fisiologia , Peristaltismo/fisiologiaRESUMO
Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.
Assuntos
Neoplasias Colorretais/diagnóstico , Dieta , Comportamento Alimentar , Inflamação/diagnóstico , Avaliação Nutricional , Adulto , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Europa (Continente)/epidemiologia , Exercício Físico/fisiologia , Feminino , Humanos , Inflamação/epidemiologia , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/fisiopatologia , Estudos Prospectivos , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.