PUBLICATIONS

In this study researchers were looking for genetic, environmental, and microbial factors that may be influence the intestinal permeability of our healthy subjects. Why was intestinal permeability looked at? Intestinal permeability is a measure of “leakiness” of the gut. Increased intestinal permeability, or leakiness, may thus allow passage of gut contents (food, bacteria etc.) which can trigger an intestinal inflammatory response. Several studies have documented that changes in intestinal permeability can predict the course of IBD. What is the LacMan Ratio? It is a tool used to assess intestinal permeability. To find this ratio, Subjects drink a solution that contains a large molecule (lactulose) that can only cross the gut barrier when it is damage. The solution also contains a small molecule (mannitol) that always crosses the barrier, independent of any damage to the gut barrier. So, by measuring the ratio of the two molecules (LacMan ratio), scientist can tells us how well the intestines are doing their job. What did this study find? The LacMan ratio was found to not be heritable, meaning that genetics may only play a small role in healthy intestinal permeability. The ratio was also not affected by microbial composition. From this we can postulate that other factors such as the environment, would then likely have a greater impact on the deterioration of healthy intestinal permeability. Kevans D, Turpin W, Madsen K, Meddings J, Shestopaloff K, Xu W, Moreno-Hagelsieb G, Griffiths A, Silverberg MS, Paterson A, Croitoru K; GEM Project. Inflamm Bowel Dis. 2015 Apr;21(4):879-87. doi: 10.1097/MIB.0000000000000323. http://www.ncbi.nlm.nih.gov/pubmed/25734694

Abstract

BACKGROUND:

The Genetics, Environmental, Microbial Project is a multicenter study assessing etiological factors in Crohn's disease by studying healthy first-degree relatives (FDRs) of individuals affected by Crohn's disease. We aimed to evaluate the contribution of genetic, microbial, and environmental factors to the determination of intestinal permeability in healthy FDRs.  

METHODS:

IP was assessed using the lactulose-mannitol ratio (LacMan ratio). FDRs were genotyped for 167 inflammatory bowel disease-associated single nucleotide polymorphisms. Taxonomic profile of the fecal microbiota was determined by Illumina MiSeq pyrosequencing of 16S ribosomal RNA. The associations of LacMan ratio with demographic factors, inflammatory bowel disease-associated single nucleotide polymorphisms and the fecal microbiota were assessed.  

RESULTS:

One thousand, one hundred ninety-six white FDRs were included [corrected]. Eleven percent of FDRs had an elevated LacMan ratio (≥0.03). A multivariate analysis demonstrated that younger subjects and nonsmokers had higher LacMan ratios, P = 3.62 × 10 and P = 0.03, respectively. The LacMan ratio was not significantly heritable, H2r, 0.13, P = 0.13. There was no association between any of the 167 inflammatory bowel disease-associated risk variants and LacMan ratio nor was there a correlation between fecal microbial composition and the LacMan ratio.  

CONCLUSION:

We did not find LacMan ratio to be significantly heritable suggesting that the contribution of genetic factors to the determination of intestinal permeability in healthy FDRs is modest. Environmental factors, such as smoking, are likely more important determinants. The effect of age on intestinal barrier function has been underappreciated.