Impaired barrier function by dietary fructo-oligosaccharides (FOS) in rats is accompanied by increased colonic mitochondrial gene expression

Wendy Rodenburg,Jaap Keijer,Evelien Kramer,Ingeborg Mj Bovee-Oudenhoven,Carolien Vink,Roelof Van Der Meer

doi:10.1186/1471-2164-9-144

Wendy Rodenburg, Jaap Keijer + Show 4 more

Open Access

https://doi.org/10.1186/1471-2164-9-144

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Journal: BMC Genomics	Publication Date: Mar 27, 2008
Citations: 126	License type: cc-by

Affiliation: TiFN, Nederlands Instituut Voor Zuivel Oonderzoek

Abstract

BackgroundDietary 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.ResultsAmong 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.ConclusionWe conclude that altered energy metabolism may underly colonic barrier function disruption due to FOS feeding in rats.

Highlights

Dietary non-digestible carbohydrates stimulate the gut microflora and are presumed to improve host resistance to intestinal infections
Body weight gain, and intestinal permeability Rats on the control diet and FOS diet showed no significant difference in body weight gain
Intestinal permeability was examined by measurement of chromium ethylenediamine-tetraacetic acid (CrEDTA) excretion in urine and showed that FOS fed rats had increased urinary excretion of this inert permeability marker as compared to the control group (Figure 1)

Summary

Introduction

Dietary non-digestible carbohydrates stimulate the gut microflora and are presumed to improve host resistance to intestinal infections. Several strictly controlled rat infection studies showed that non-digestible fructo-oligosaccharides (FOS) increase, rather than decrease, translocation of Salmonella towards extra-intestinal sites. Non-digestible carbohydrates like fructo-oligosaccharides (FOS) stimulate the gut microflora and are presumed to improve host resistance to intestinal infections. There is little evidence that these non-digestible carbohydrates strengthen intestinal resistance to infection and gut barrier function For this reason, several strictly controlled rat infection studies were previously performed at our lab. Several strictly controlled rat infection studies were previously performed at our lab These studies consistently showed that the non-digestible carbohydrates inulin, lactulose and FOS increase translocation of Salmonella to extra-intestinal organs [3,4,5]. Luminal cytotoxicity and faecal mucin excretion were increased in FOS-fed rats and may indicate mucosal irritation [5]

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