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Updated: Jul 6, 2026
Assessment of Gut Barrier Integrity in Mice Using Fluorescein-Isothiocyanate-Labeled Dextran
Published on: November 18, 2022
Impaired barrier function by dietary fructo-oligosaccharides (FOS) in rats is accompanied by increased colonic
Wendy Rodenburg1, Jaap Keijer, Evelien Kramer
1TI Food and Nutrition, Wageningen, The Netherlands. wendy.rodenburg@rivm.nl
Background:
Dietary non-digestible carbohydrates stimulate the gut microflora and are therefore presumed to improve host resistance to intestinal infections. However, several strictly controlled rat infection studies showed that non-digestible fructo-oligosaccharides (FOS) increase, rather than decrease, translocation of Salmonella towards extra-intestinal sites. In addition, it was shown that FOS increases intestinal permeability already before infection. The mechanism responsible for this adverse effect of FOS is unclear. Possible explanations are altered mucosal integrity due to changes in tight junctions or changes in expression of defense molecules such as antimicrobials and mucins. To examine the mechanisms underlying weakening of the intestinal barrier by FOS, a controlled dietary intervention study was performed. Two groups of 12 rats were adapted to a diet with or without FOS. mRNA was collected from colonic mucosa and changes in gene expression were assessed for each individual rat using Agilent rat whole genome microarrays.
Results:
Among the 997 FOS induced genes we observed less mucosal integrity related genes than expected with the clear permeability changes. FOS did not induce changes in tight junction genes and only 8 genes related to mucosal defense were induced by FOS. These small effects are unlikely the cause for the clear increase in intestinal permeability that is observed. FOS significantly increased expression of 177 mitochondria-related genes. More specifically, induced expression of genes involved in all five OXPHOS complexes and the TCA cycle was observed. These results indicate that dietary FOS influences intestinal mucosal energy metabolism. Furthermore, increased expression of 113 genes related to protein turnover, including proteasome genes, ribosomal genes and protein maturation related genes, was seen. FOS upregulated expression of the peptide hormone proglucagon gene, in agreement with previous studies, as well as three other peptide hormone genes; peptide YY, pancreatic polypeptide and cholecystokinin.
Conclusion:
We conclude that altered energy metabolism may underly colonic barrier function disruption due to FOS feeding in rats.
Insights
Dietary fructo-oligosaccharides (FOS) may disrupt the gut barrier by altering energy metabolism, not by affecting mucosal integrity. This study investigated the mechanisms behind FOS-induced increases in intestinal permeability in rats.
Area of Science:
- Gut Microbiome Research
- Molecular Biology
- Nutritional Science
Background:
- Dietary non-digestible carbohydrates like fructo-oligosaccharides (FOS) are thought to enhance gut health.
- However, studies show FOS can increase Salmonella translocation and intestinal permeability in rats.
- The underlying mechanisms for FOS's adverse effects on the intestinal barrier remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms by which FOS weakens the intestinal barrier.
- To examine the impact of FOS on mucosal integrity, tight junctions, and defense molecule expression.
- To explore FOS's effects on colonic gene expression related to barrier function.
Main Methods:
- A controlled dietary intervention study was conducted with rats fed diets with or without FOS.
- Colonic mucosal mRNA was collected from individual rats.
- Whole-genome microarrays were used to assess changes in gene expression.
Main Results:
- FOS did not significantly alter genes related to mucosal integrity or tight junctions.
- Only a small number of mucosal defense genes were affected by FOS.
- FOS significantly increased the expression of 177 mitochondria-related genes, impacting energy metabolism (OXPHOS, TCA cycle).
- Increased expression of genes involved in protein turnover and peptide hormones (proglucagon, peptide YY, pancreatic polypeptide, cholecystokinin) was also observed.
Conclusions:
- Altered energy metabolism, indicated by changes in mitochondrial gene expression, may be the primary mechanism behind FOS-induced disruption of colonic barrier function.
- FOS does not appear to weaken the intestinal barrier by directly impacting mucosal integrity or tight junctions.
