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Inflammatory bowel disease is associated with increased gut‐to‐blood penetration of short‐chain fatty acids: A new, non‐invasive marker of a functional intestinal lesion
Author(s) -
Jaworska Kinga,
Konop Marek,
Bielinska Klaudia,
Hutsch Tomasz,
Dziekiewicz Marcin,
Banaszkiewicz Aleksandra,
Ufnal Marcin
Publication year - 2019
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep087773
Subject(s) - intestinal permeability , inflammatory bowel disease , medicine , gastroenterology , short chain fatty acid , gut flora , barrier function , pathology , disease , biology , immunology , biochemistry , butyrate , fermentation , microbiology and biotechnology
New FindingsWhat is the central question of this study? ‘Leaky gut’ has been found in intestinal and extra‐intestinal diseases. However, functional evaluation of intestinal permeability is not widely used as a diagnostic marker, possibly owing to significant limitations of currently used permeability assays. There is an unmet need for development of a new, non‐invasive test to assess intestinal function.What is the main finding and its importance? We show that an increased blood‐to‐stool ratio of the concentration of gut bacteria‐produced short‐chain fatty acids may be used as a marker of gut permeability. Our findings lay the groundwork for establishing a new, non‐invasive, risk‐free diagnostic tool in diseases associated with intestinal barrier malfunction, such as inflammatory bowel disease.Abstract Intestinal diseases, such as inflammatory bowel disease (IBD), are characterized by an impaired gut–blood barrier commonly referred to as ‘leaky gut’. Therefore, functional evaluation of the gut–blood barrier is a promising diagnostic marker. We hypothesized that short‐chain fatty acids (SCFAs) produced by gut bacteria might serve as a marker in IBD. Animal experiments were performed on male Sprague–Dawley rats with acetic acid‐induced colitis and in sham control animals. The gut–blood barrier permeability was determined by assessing the ratios of the following: (i) portal blood concentration of SCFAs ( C p ) to faecal concentration of SCFAs ( C f ); (ii) systemic blood concentration of SCFAs ( C s ) to faecal concentration of SCFAs ( C f ); and (iii) C p and C s of fluorescein isothiocyanate (FITC)–dextran administered into the colon. As a clinical study, we evaluated C s , C f and the C s / C f ratio of SCFAs in six paediatric patients with IBD, assessed as mild/moderate/severe by the Paediatric Ulcerative Colitis Activity Index (PUCAI) and the Paediatric Crohn's Disease Activity Index (PCDAI) at the time of sample collection, and nine age‐matched healthy control subjects. Rats with histologically confirmed IBD had significantly increased ratios of C p / C f and C s / C f for SCFAs. This was positively correlated with the plasma FITC–dextran concentration. Likewise, IBD patients showed a significantly higher C s / C f ratio for SCFAs, including acetic, valeric, isocaproic, caproic and propionic acids, in comparison to control subjects. In conclusion, in the rats and in paediatric patients with IBD we found an increased blood‐to‐stool ratio of SCFAs, suggesting an increased gut‐to‐blood penetration of SCFAs. These findings pave the way for a new, non‐invasive diagnostic tool in IBD and other diseases accompanied by intestinal barrier malfunction.