1. Conclusion and Acknowledgement
Comparative levels of butyrate transporters in ulcerative colitis,
Crohn’s disease and normal patients.
S Roux, S Daniell and ES Fredericks
Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
Introduction
Butyrate
Butyrate transport
Butyrate transporters
SCFAs are transported into the colonic epithelial cells by:
Passive non-ionic diffusion and
Specific carrier-mediated transport of SCFA.
Carrier-mediated transport is the preferred method:
(i) Electroneutral H+-coupled monocarboxylate transporter (MCT). The proton-linked MCT is carried out by members of the SCL16 family. MCT1 (SCL16A1) requires a chaperone protein, CD147, as co-transporter for butyrate transport via MCT takes place in a 1: 1 ratio. When butyrate levels in lumen are low, MCT1 is the preferred transporter.
(ii) Electrogenic Na+-coupled monocarboxylate transport (SMCT). SMCT1 (SLC5A8) are Na+-coupled MCTs with a Na+/monocarboxylate stoichiometry of 4:1.
Short chain fatty acids (SFCA), butyrate, acetate and propionate, are products of bacterial fermentation on undigested food rests by colonic flora. Butyrate, plays a key role in colonic epithelium homeostasis and represents the main fuel for colonocytes. It has anti-inflammatory properties and promotes cellular differentiation probably via the up-regulation of the transcription factor PPARϒ.
It is suggested that a dysregulation in the metabolism and uptake of butyrate into colonocytes precipitate the inflammation in inflammatory bowel disease (IBD) patients and that there may be a down regulation of MCT1 and/or SMCT1 in colonocytes of IBD patients.
AIM: To analyse and compare MCT1 and SMCT1 levels in colon biopsy samples of normal (n=19), ulcerative colitis (n=9) and Crohn’s disease (n=8) patients.
Method
Demographic details
Statistical analysis: ANOVA and Mann Whitney test
Normalization of MCT1 and SMCT1 versus 3 reference genes
PCR quantification of mRNA (BioRad iQ™ SYBR® Green Supermix).
SCFA analysed with GC/MS
Colonoscopy, proximal colon biopsy samples stored in RNAlater at -200C.
Stool samples stored at -800C
Ethical approval obtained (H07SciBCM-001), patients signed informed consent
Demographic details of study population
Normal
Crohn’s disease
Ulcerative colitis
Total number 19 8 9
Male
36.8%
50%
44.4%
Female
63.2%
55.6%
Age
53.0
43.5
BMI
25.54
21.17
25.96
Smoke
23.1%
62.5%
7.1%
NSAID use
26.3% 0%
Results #
#:P < 0.05 vs normal #
Conclusion and Acknowledgement
Only in UC patients stool butyrate concentration was significantly decreased vs normal.
Lower availability of butyrate in the stool did not up-regulate transporters as expected.
Lack of butyrate transporters UC patients may contribute to inflammation
Literature shows TNFα causes a down-regulation of both MCT1 and SMCT1. Anti-TNFα treatment for UC patients may enhance anti-inflammatory effect of butyrate.
MCT1 most abundant transporter in colon (results not shown)
MCT1 is not affected while SMCT1 is 8 fold up-regulated in CD patients. It seems as if TNFα affects butyrate transporters in UC patients but not in CD patients. UC is a superficial mucosal inflammatory condition while CD is a transmural inflammatory disease.
Butyrate releasing probiotics may benefit CD patients.
Regulation of butyrate transporters needs further research.
We want to thank the NRF for funding and Mr Cameron Batteson for determining the SCFA