The metabolic activity of the gut microbiota and the impact of gluten free diet in children with coeliac disease

Abstract

The role of the gut microbiota in coeliac disease (CD) is unclear and evidence remains inconclusive (1,2) . This study investigated the metabolic activity of the gut microbiota in patients with long standing CD (LS), healthy siblings of CD patients (HS), newly diagnosed CD patients (ND) followed from diagnosis up to one year of gluten free diet (GFD) and healthy controls (HC).Faecal pH and faecal concentration of ammonia, short chain fatty acids (SCFA), branched chain fatty acids (BCFA), lactate (L and D lactate), and free and total sulphide were measured in spot samples. ND patients provided up to 3 samples (at diagnosis, 6 and 12 month on GFD).Forty three (23 females, age 9.3 ± 4.3) LS, 23 HS (13 females, age 9 ± 4.6), 11(6 females, 11.4 ± 2.4) ND and 57 HC (30 females, age 8 ± 4.2) participated in the study. The concentrations of propionate (p = 0.024), butyrate (p = 0.004) and valerate (p = 0.011) were significantly lower in the LS group than in HC (Table). Similarly, the concentrations of all BCFA were significantly reduced (iso-butyrate p = 0.016, iso-valeric p = 0.039, iso-caproic p = 0.025) in the LS group compared with HC (Table). There were no statistically significant differences in the concentration of SCFA and BCFA between LS and HS. Total sulphide was significantly increased in the LS group compared to the HC group (p = 0.027).No significant changes were observed in the concentrations of SCFA in ND during GFD. However, compared to disease diagnosis, faecal sulphide significantly increased after 6 (p = 0.014) and 12 months on GFD (p = 0.022).Major changes were observed in the concentration of faecal bacterial metabolites between children with LS and HC. The reason for these differences is not yet clear but may be explained by the resolution of gastrointestinal malabsorption and the different dietary patterns of those who adhere to a gluten free diet. This study was funded by the Nutricia Research Foundation.

How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review

“…Conversely to the four earlier cited studies ( Di Cagno et al, 2009 , 2011 ; Makinder et al, 2014 ; Zafeiropoulou et al, 2020 ), Nistal et al (2012) showed that T-CD had the highest concentration of fecal SCFAs. More in-depth, this class of FAs was markedly affected by the higher levels of acetic, propionic, and butyric acids compared to HC under a gluten-containing diet.…”

“…However, some fecal metabolites significantly characterized T-CD, such as a lower fecal concentration of ammonia (vs. HC and U-CD) and D-lactic acid (vs. U-CD) and a higher concentration L-lactic acid (vs. U-CD). Also, Makinder et al’s (2014) study, the concentration of total SCFA and branched-chain fatty acids (BCFAs) did not differ between T-CD and HS, whereas propionic, butyric, and valeric acids as well as iso -butyrate, iso -valeric, and iso -caproic were significantly lower in the same T-CD than HC. In T-CD, the authors also assessed a higher value of total sulfide than HC.…”

“…Among these differences, only the significance related to iso -butyric acid extended to 12 months. Similarly, Makinder et al (2014) enrolled U-CD that provided feces after 6 and 12 months of GFD, but in this case the dietary gluten deprivation did not determine changes in levels of SCFAs. Instead, the authors noticed a significant increase in fecal sulfide after both 6 and 12 months on GFD ( Makinder et al, 2014 ).…”

Effects of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei supplementation on the faecal metabolome in children with coeliac disease autoimmunity: a randomised, double-blinded placebo-controlled clinical trial

“…Especially in CD, SCFAs are of major interest due to their involvement in immunomodulatory functions such as the production of regulatory T-cells (19). Some studies also reported alterations in SCFA production in CD patients (20)(21)(22), even when on a long-term gluten-free diet (23). Other metabolites with altered amounts in CD are glutamine and tryptophan, which also impact the immune system (24,25).…”