uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBD
Baghdad University/ College of Veterinary Medicine. (Medical Sciences/Gastroenterology and Hepatology)ORCID iD: 0000-0002-4842-3227
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. (Gastroenterology/Hepatology)ORCID iD: 0000-0001-6220-3936
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. (Gastroenterology and Hepatology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.ORCID iD: 0000-0002-6979-9194
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Hyper-permeability in inflammatory bowel disease (IBD) has mostly been explored in the colon, where symptomatic inflammation is prevalent. Relationships between small and large intestine barrier function were examined. Fasted (4h) IBD (19 ulcerative colitis, 11 Crohn's disease) and 25 healthy control subjects’ were investigated. Lactulose (10g), mannitol (5g), riboflavin (0.05g) and sucralose (5g) were ingested with 500 mL water. Urine lactulose and mannitol were measured by enzyme assays, riboflavin by intrinsic fluorescence and sucralose by HPLC. CRP was measured by nephelometry. In IBD, small intestine lactulose and sucralose % recoveries were 1.77 and 2.73 fold higher than controls; combined data revealed the two probes were correlated (R2=0.6). In IBD, large intestine sucralose % recovery was 2.6 fold higher than controls and correlated with small intestine sucralose % recovery (R2=0.6). Conclusions: Sucralose yields similar result as lactulose for small intestine permeability, while having higher S:N, implying sucralose is more sensitive. No evidence was found for riboflavin malabsorption in IBD. There is concurrent small and large intestine hyper-permeability in IBD. Small intestine hyper-permeability is presumably related to inflammation in the large intestine, but without obvious deficiency in transporter mediated micronutrient absorption (i.e., riboflavin) in the small intestine.

Keywords [en]
Crohn’s disease; Ulcerative colitis; Sucralose; Tight junction; Permeability; Intestine
National Category
Clinical Medicine Gastroenterology and Hepatology
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-383487OAI: oai:DiVA.org:uu-383487DiVA, id: diva2:1316181
Available from: 2019-05-16 Created: 2019-05-16 Last updated: 2019-05-17
In thesis
1. Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease
Open this publication in new window or tab >>Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Synchronized motility, permeability and secretory (hormones and enzymes) events are integral to normal physiology. Smooth muscle syncytium operates with enteric nervous system (ENS) and endocrine signalling to accommodate, mix and control passage of ingested materials. The intestinal epithelial cells (IECs) drive digestion and absorption while repelling harmful compounds.

This thesis investigated GI barrier function (permeability, mucosal integrity), motility and hormonal patterns in inflammatory bowel disease (IBD) by: 1) assessing GI motility using a wireless motility capsule (WMC, SmartPill®) and video capsule endoscopy (VCE, Pillcam®), 2) investigation of intestinal fatty acid binding protein (I-FABP) as a biomarker of Crohn’s disease (CD) disease activity, 3) evaluation of small intestinal permeability in IBD, 4) investigating meal-related WMC motility and simultaneous hormonal (e.g., Ghrelin, GLP-1, GIP, PYY) patterns in IBD. Reference WMC motility values for transit times for gastric emptying, small bowel, orocecal, small+large bowel, colon and whole gut were established. Software-generated estimates and visually determined values were nearly identical. Compared with VCE estimates (represents fasting conditions), the WMC records longer GET and SBTT. Variations in intra-subject reproducibility must be considered in clinical investigations. This data was then used to investigate IBD patients. I-FABP was primarily expressed in the epithelium of the small bowel and to lesser extent also in the colon and stomach. Circulating I-FABP was elevated in active CD with a magnitude comparable to TNFα. I-FABP lowers and rises again in parallel with TNFα and HBI during infliximab treatment. I-FABP can be used as a jejunum and ileum selective prognostic biomarker for monitoring disease activity. Increased small intestine mucosal barrier permeability to lactulose in both CD and UC was found. Sucralose can serve a dual purpose in quantifying small and large intestinal permeability. Small intestinal hyper-permeability was not revealed as a transporter dependent nutrient (riboflavin) malabsorption. Using the WMC, consistent motility disturbances in IBD were limited, as were differences in pH. However, disturbances within many individuals were found. As part of the investigation, defects in gut peptide and metabolic hormone meal responses were found, typically higher plasma levels. No clear associations between hormones and motility were found. Effects on hunger/satiety signaling in IBD are anticipated.

The present thesis shows the utility of the WMC and gut barrier tests in monitoring IBD patients.

Abstract [sv]

Mag-tarmkanalens glatta muskulatur är funktionellt integrerad med enteriska nervsystemet och endokrin signalering för ackommodation, blandning och passage genom mag-tarmkanalen. De intestinala epitelcellerna upprätthåller digestion och absorption, samtidigt med barriärfunktion mot skadliga agens.

Avhandlingen utvärderar patofysiologiska barriärmekanismer vid inflammatorisk tarmsjukdom (IBD) beträffande permeabilitet, förändrad motilitet och hormonella mönster vid Crohns sjukdom (CD) och ulcerös colit (UC) genom att, 1) utvärdera mag-tarmkanalens motilitet med trådlös motilitetskapsel (WMC) och videokapsel endoskopi (VCE), 2) studera I-FABP som biomarkör vid CD avseende distribution i mag-tarmkanalen, samband med sjukdomsktivitet, parallellitet med  TNFα och Harvey-Bradshaw index (HBI) under anti-TNFα-behandling, 3) utvärdera intestinal permeabilitet vid IBD, 4) studera användning av WMC för att registrera motilitet vid måltidssvar och hormonella mönster.

WMC registrerade pH, tryck och temperatur längs hela mag-tarmkanalen. Referensvärden för  ventrikeltömningstid och transittider för tunntarm, colon och totala mag-tarmkanalen etablerades. Dessa värden har använts för utvärdering av IBD. Mjukvaruberäknade värden var lika visuellt avlästa värden. Mätvärden för VCE under fasta visade snabb transit, medan WMC hade längre ventrikeltömningstid och transittid för tunntarm. Intra-individuell variation måste bedömas särskilt vid kliniska undersökningar.

I-FABP lokaliserades till epitelet i tunntarmen, i mindre omfattning i ventrikel och colon. Cirkulerande I-FABP var förhöjt vid aktiv CD, som TNFα. Plasmanivåer av I-FABP följde parallellt TNFα och HBI under behandling och uppföljning. I-FABP kan användas som selektiv prognostisk markör för CD i jejunum och ileum vid monitorering av CD patienter.

Ökad tunntarmspermeabilitet sågs både vid CD och UC med hyperpermeabilitet för laktulos, medan sukralos, som ersättning för laktulos, kunde mäta permeabilitet i både tunntarm och colon. Hyperpermeabiliteten medför ingen generell malabsorption eftersom absorptionen av riboflavin var normal, och beror av specifika transportmekanismer i tunntarmen.

Med hjälp av WMC kunde endast begränsade avvikelser i motiliteten vid IBD registreras, även för pH. Hos enskilda individer kunde tydliga avvikelser ses. Dessutom noterades generellt förhöjda gastrointestinala och metabola peptidhormoner samtidigt med ett bevarat måltidssvar. Samband mellan hormonnivåer och motilitetsavvikelser saknades, men sannolikt har hormonnivåerna betydelse för hunger och mättnad.

Den sammantagna bilden visar användbarheten av WMC och permeabilitetstest för att bedöma patofysiologiska funktioner i mag-tarmkanalen. I-FABP kan spåra sjukdomsaktivitet i tunntarmen, medan permeabilitetstest ger information selektivt om sjukdom i tunntarm och colon. Användning av WMC tillsammans med mönster av hormonfrisättning kan ge information om motilitetsstörningar och sannolikt förändrad aptitreglering.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1577
Keywords
Gastrointestinal motility, intestinal permeability, Mucosal, Ghrelin
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-382486 (URN)978-91-513-0671-1 (ISBN)
Public defence
2019-06-14, Enghoffsalen, Ing 50 bv, Akademiska sjukhuset, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2019-05-23 Created: 2019-04-25 Last updated: 2019-06-17

Open Access in DiVA

No full text in DiVA

Authority records BETA

Al-Saffar, Anas Kh.Halim, AbdulHellström, Per M.Webb, Dominic-Luc

Search in DiVA

By author/editor
Al-Saffar, Anas Kh.Halim, AbdulHellström, Per M.Webb, Dominic-Luc
By organisation
Gastroenterology/Hepatology
Clinical MedicineGastroenterology and Hepatology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 169 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf