Effect of gluten and FODMAP elimination in celiac patients on gut inflammatory biomarkers

Abstract

Background: Reduced dietary intake of fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) has been suggested as a strategy to improve gastrointestinal (GI) symptoms in people diagnosed with irritable bowel syndrome (IBS). In a Norwegian study of patients with celiac disease (CD), experiencing persistent GI symptoms similar to those observed in IBS-patients, reducing FODMAPs gave symptom relief. Based on the same study, the aim of the current master thesis was to investigate the effects of FODMAP restriction on fecal neutrophil gelatinaseassociated lipocalin (NGAL); a potential biomarker of gut integrity and inflammation, and effects on the concentration of fecal short-chain fatty acids (SCFAs); metabolites of microbial fermentation. Also, the associations between GI symptoms and fecal NGAL and SCFA were investigated. Furthermore, the potential for using a Luminex-based method for measuring fecal NGAL, as an alternative to ELISA, was investigated. Methods: The study, which followed a randomized parallel design, included adult CD patients on a gluten-free diet (GFD) having persistent GI symptoms. The participants were randomized to consume a low-FODMAP diet (LFD) in addition to their GFD (LFD-group, n=34) or to continue their regular GFD (controls, n=36) and were followed up for four weeks as out-patients at the clinic of Oslo University. Sampling of feces was performed at baseline and at 4-week follow-up. NGAL was measured in fecal extracts using ELISA, while fecal SCFAs were analysed using GCFID technology. Also, a Luminex-based method was established, and compared to that of ELISA. Results: Reducing the intake of FODMAPs did not affect fecal NGAL levels when comparing 4-week values between the LFD group and the controls using a linear regression model, controlling for baseline values. Similar linear regression models analysing the SCFAs indicated a significant effect of the intervention (p<0.05) for propionic acid and valeric acid, but the effects on both SFCAs were dependent on the baseline levels with a reduction only in those with initially high baseline levels. No differences between the groups were found for the remaining SCFAs. A Luminex microbead-based method for measuring NGAL in fecal samples was successfully established. Still, it showed higher concentrations than the ELISA method, and systematic proportional bias was detected when investigating the agreement between the methods. Several samples measured by the Luminex technology did not reach the limit of detection with ELISA. Conclusion: Although the LFD reduced GI symptoms in CD patients with persistent GI symptoms, this was not reflected by changes in the inflammation associated biomarker NGAL indicating that the GI symptoms in the current study is not related to inflammation but may be caused by other FODMAP associated factors such as osmotic effects followed by mechanic stress. The effects of the FODMAP reduction on propionic acid and valeric acid also indicate possible changes in microbial communities which may affect the amounts of intestinal gasses produced. Further studies should explore the usefulness of NGAL as a biomarker of intestinal inflammation in CD and more directly explore the effects of LFD on intestinal gut microbiota.