INTRODUCTION: Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract, leading to organ damage. IBDs include Crohn’s Disease (CD), Ulcerative Colitis (UC) and Indeterminate Colitis (IBD-U). In terms of their etiology, an altered intestinal permeability seems to be an important factor, since it leads to an increased intake of toxins and antigens. The word leaky gut is used to convey the idea that intestinal permeability is increased, with the epithelial barrier getting less selective. There has been evidence that a leaky gut is related to several diseases, gastrointestinal and non-gastrointestinal. AIM OF THE STUDY: to evaluate: i) intestinal permeability in a IBD cohort and in a cohort of asymptomatic controls (AC); ii) the correlation between intestinal permeability, psychological conditions, and the quality of life. MATERIALS AND METHODS: the study is longitudinal and prospective. Thirty-six patients with a diagnosis of IBD were selected. The inclusion criteria were, for the IBD cohort, the presence of active disease, and, for the AC cohort, the lack of disease. Once enrolled, the patient was given a kit for the evaluation of intestinal permeability via a multi-sugar test (mannitol, lactulose, sucrose, and sucralose). In addition, a blood sample was collected, to measure the level of the hormone FGF-19 in the serum. The amount of urinary sugars was measured with HPLC-MS and the blood concentrations of FGF-19 were measured with Human FGF-19 Quantikine ELISA kit. Lastly, to evaluate the psychophysical wellbeing of the enrolled patients, three different questionnaires were delivered: HADS, SF-36 and a 46-items questionnaire assessing digestive symptoms. The statistical analysis was performed by the means of STATA11 software packages, carrying through non-parametric statistic tests. RESULTS: compared to the AC group, in CD patients mannitol (p<0.01) was significantly decreased, whilst lactulose to mannitol ratio or LMR (p=0.05), sucrose (p<0.001) and sucralose (p<0.05) were significantly increased. Compared to the AC group, sucrose (p<0.01) was significantly increased in UC patients. Serum levels of FGF-19 were significantly different between the three groups (p=0.05) and decreased, compared to the AC group, for both CD patients (p<0.05) and UC patients (p=0.05). Assessing the results of the questionnaires, CD patients, compared to the AC group, were more physically (p<0.001) and emotionally (p<0.001) affected, showing a decreased vitality (p<0.001), a perceived stronger pain (p=0.001) and worse general health (p=0.002). Patients with UC, compared to the AC group, had higher scores in HADS-A (p=0.001) and HADS-D (<0.001), showing worse well-being both physically (p<0.001) and emotionally (p<0.001), with a decrease in vitality (p<0.001) and social functioning (p<0.001). . CONCLUSIONS: patients with IBD have shown an increased intestinal permeability compared to the AC, confirmed by increased urinary sugar levels and decreased levels of serum FGF-19. In the IBD cohort, CD patients had an overall higher variability in the urinary excretion of sugars than the AC group. Hence, the clinical relevance of the data seems to be bigger in CD than in UC. The psychophysical well-being in the IBD cohort has been shown as worse overall than in the AC group. It appears to be difficult, though, to establish a causative link between the leaky gut and psychophysiological disorders, taking out the burden of the chronic disease per se.
INTRODUZIONE: le malattie infiammatorie croniche dell’intestino (MICI) sono patologie a eziologia multifattoriale con interessamento di diversi segmenti del tubo gastroenterico, inducendo un danno d’organo. Esse comprendono la malattia di Crohn (MC), la rettocolite ulcerosa (RCU) e la colite indeterminata (IBD-U). A livello eziologico, uno dei fattori coinvolti sembra essere l’aumentata permeabilità intestinale, che predispone all’ingresso di tossine e antigeni. In generale, con il termine leaky gut si intende una condizione per cui si sviluppa un’aumentata permeabilità intestinale, con perdita della selettività della barriera epiteliale. Sono diverse le evidenze di associazioni tra il leaky gut e numerose patologie, gastroenterologiche e non. SCOPO DELLO STUDIO: valutare: i) la permeabilità intestinale in una coorte di pazienti con MICI e in una coorte di controlli sani; ii) le correlazioni tra le alterazioni della permeabilità intestinale, le condizioni psicologiche e la qualità di vita. MATERIALI E METODI: lo studio condotto è longitudinale prospettico. Sono stati selezionati 36 pazienti con diagnosi di MICI, con i criteri d'inclusione che sono stati, per il gruppo MICI, la presenza di attività di malattia, e, per i controlli sani, l’assenza di patologia. Ai pazienti e ai controlli veniva consegnato un kit per lo studio della permeabilità intestinale ai quattro zuccheri, in particolare mannitolo, lattulosio, saccarosio e sucralosio, e veniva prelevato del sangue per il dosaggio dei livelli circolanti dell’ormone FGF-19. La quantità di zuccheri escreta con le urine è stata misurata mediante HPLC-MS, mentre le concentrazioni sieriche di FGF-19 mediante kit Human FGF-19 Quantikine ELISA. Infine, per la valutazione del benessere psicofisico, sono stati dispensati tre diversi questionari: HADS, SF-36 e un questionario sui sintomi digestivi a 46 items. L’analisi statistica è stata portata avanti mediante software STATA11 e sono stati impiegati test d'ipotesi non parametrici RISULTATI: rispetto al gruppo di controlli asintomatici (AC), nei pazienti con malattia di Crohn (MC), il mannitolo (p<0.01) è risultato significativamente diminuito, mentre il lactulose to mannitol ratio, o LMR (p=0.05), il saccarosio (p<0.001) e il sucralosio (p<0.05) significativamente aumentati. Rispetto ad AC, nei pazienti con RCU il saccarosio (p<0.01) si è visto significativamente aumentato. I livelli sierici di FGF-19 sono risultati statisticamente differenti tra i tre gruppi (p=0.05) e diminuiti, rispetto ad AC, sia per MC (p<0.05) sia per RCU (p=0.05). Dai questionari è emerso che, rispetto ad AC, i pazienti con MC presentano un peggiore benessere fisico (p<0.001), un benessere emotivo più scarso (p<0.001), una vitalità ridotta (p<0.001), un dolore percepito maggiore (p=0.001) e peggiori condizioni di salute generale (p=0.002). I pazienti con RCU, rispetto ad AC, presentano scores psicometrici di ansia (p=0.001) e depressione (<0.001) più elevati, un peggior benessere fisico (p<0.001), un benessere emotivo più scarso (p<0.001), una vitalità ridotta (p<0.001) e capacità sociali ridotte (p<0.001). CONCLUSIONI: i pazienti con MICI presentano un’aumentata permeabilità intestinale rispetto ai controlli sani asintomatici, confermata da un’aumentata escrezione degli zuccheri somministrati e da ridotti livelli sierici di FGF-19. All’interno del gruppo MICI, il gruppo MC presenta una maggiore variabilità rispetto al gruppo dei controlli sull’escrezione urinaria degli zuccheri. Pertanto, la rilevanza clinica del dato sembra appannaggio della MC rispetto alla RCU. Il benessere psicofisico si è visto fortemente ridotto sia nella MC sia nella RCU rispetto ai controlli, risultando, però, difficile stabilire un rapporto causale tra il leaky gut e lo sviluppo di disturbi psicofisici, non considerando il peso della patologia organica cronica di per sé.
STUDIO PROSPETTICO DI VALUTAZIONE DELLA PERMEABILITÀ INTESTINALE IN PAZIENTI CON MALATTIE INFIAMMATORIE CRONICHE DELL'INTESTINO: QUALE RUOLO DEL "LEAKY GUT"?
FRASCA, PIERLUIGI
2021/2022
Abstract
INTRODUCTION: Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract, leading to organ damage. IBDs include Crohn’s Disease (CD), Ulcerative Colitis (UC) and Indeterminate Colitis (IBD-U). In terms of their etiology, an altered intestinal permeability seems to be an important factor, since it leads to an increased intake of toxins and antigens. The word leaky gut is used to convey the idea that intestinal permeability is increased, with the epithelial barrier getting less selective. There has been evidence that a leaky gut is related to several diseases, gastrointestinal and non-gastrointestinal. AIM OF THE STUDY: to evaluate: i) intestinal permeability in a IBD cohort and in a cohort of asymptomatic controls (AC); ii) the correlation between intestinal permeability, psychological conditions, and the quality of life. MATERIALS AND METHODS: the study is longitudinal and prospective. Thirty-six patients with a diagnosis of IBD were selected. The inclusion criteria were, for the IBD cohort, the presence of active disease, and, for the AC cohort, the lack of disease. Once enrolled, the patient was given a kit for the evaluation of intestinal permeability via a multi-sugar test (mannitol, lactulose, sucrose, and sucralose). In addition, a blood sample was collected, to measure the level of the hormone FGF-19 in the serum. The amount of urinary sugars was measured with HPLC-MS and the blood concentrations of FGF-19 were measured with Human FGF-19 Quantikine ELISA kit. Lastly, to evaluate the psychophysical wellbeing of the enrolled patients, three different questionnaires were delivered: HADS, SF-36 and a 46-items questionnaire assessing digestive symptoms. The statistical analysis was performed by the means of STATA11 software packages, carrying through non-parametric statistic tests. RESULTS: compared to the AC group, in CD patients mannitol (p<0.01) was significantly decreased, whilst lactulose to mannitol ratio or LMR (p=0.05), sucrose (p<0.001) and sucralose (p<0.05) were significantly increased. Compared to the AC group, sucrose (p<0.01) was significantly increased in UC patients. Serum levels of FGF-19 were significantly different between the three groups (p=0.05) and decreased, compared to the AC group, for both CD patients (p<0.05) and UC patients (p=0.05). Assessing the results of the questionnaires, CD patients, compared to the AC group, were more physically (p<0.001) and emotionally (p<0.001) affected, showing a decreased vitality (p<0.001), a perceived stronger pain (p=0.001) and worse general health (p=0.002). Patients with UC, compared to the AC group, had higher scores in HADS-A (p=0.001) and HADS-D (<0.001), showing worse well-being both physically (p<0.001) and emotionally (p<0.001), with a decrease in vitality (p<0.001) and social functioning (p<0.001). . CONCLUSIONS: patients with IBD have shown an increased intestinal permeability compared to the AC, confirmed by increased urinary sugar levels and decreased levels of serum FGF-19. In the IBD cohort, CD patients had an overall higher variability in the urinary excretion of sugars than the AC group. Hence, the clinical relevance of the data seems to be bigger in CD than in UC. The psychophysical well-being in the IBD cohort has been shown as worse overall than in the AC group. It appears to be difficult, though, to establish a causative link between the leaky gut and psychophysiological disorders, taking out the burden of the chronic disease per se.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/30985