This post is out of my usual comfort zone, but I thought I’d write about it as it is fascinating, and might lead to something clinical. I don’t understand any of the lab methodology of this study, except to say that they examined bits of DNA. Sampath V, et al. SIGIRR Genetic Variants in Premature Infants With Necrotizing Enterocolitis. Pediatrics. 2015.
What they did was to look at bits of DNA that code for something called SIGIRR in preterm infants with NEC. Toll-like receptors are cell-surface receptors that are involved in pathogen recognition and regulation of intestinal inflammation. SIGIRR is apparently the nom-de-guerre of a gene that inhibits TLR signaling, so when it doesn’t work properly you get exaggerated inflammation, and maybe NEC. The TLR which is most implicated is TLR4, which senses endotoxin from Gram-negatives, and it is this TLR which promotes inflammation when not regulated by SIGIRR (I think; someone can let me know if I am out to lunch). They tested this in an epithelial cell line to confirm the effect.
Basically a lot of the preterm babies with NEC had SIGIRR genes that were messed up. In the general population there are fewer than 400 potentially deleterious alleles in a database of 12,000 individuals. In 18 NEC cases there were 11 who had abnormal alleles. In 17 preterms without NEC they did not find any. The incidence is therefore dramatically associated with NEC and there is a strong mechanistic rationale.
The next question might be “Now what do we do about it?”
Well, not too much surprise here for regular followers of the blog, the answer is (or may be): Probiotics!
Bifidobacterial conditioned media increased mRNA levels of SIGIRR and other inflammatory regulators in this study :Ganguli K, et al. Probiotics Prevent Necrotizing Enterocolitis by Modulating Enterocyte Genes that Regulate Innate Immune-Mediated Inflammation. American Journal of Physiology – Gastrointestinal and Liver Physiology. 2012. This study and a couple of others show an effect of bifidobacteria in regulating the expression of SIGIRR, and therefore decreasing intestinal inflammation. Cool. Maybe even true.