- Anbazhagan, Arivarasu N. et al. A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity, and Inflammation. Gastroenterology, Volume 167, Issue 4, 704 - 717.e3
Inflammatory bowel diseases are associated with increased risk of hyperoxaluria and consequently nephrolithiasis due to increased enteric oxalate levels. The anion transporter PAT1, also known as SLC26A6, plays an important role in this context by transporting oxalate and bicarbonate in the gut and contributing to the maintenance of the intestinal barrier. A new study in PAT1-knockout mice (PKO) showed that the loss of this transporter leads to increased intestinal permeability and a disrupted intestinal microbiome. In particular, the reduction of tight junction proteins in the gut, protective microbes and their metabolites, such as butyrate, play an important role in the development of inflammatory processes in the gut.
The loss of PAT1 not only leads to a disrupted intestinal barrier, but also to an increased susceptibility to inflammatory bowel diseases such as colitis. In experiments with chemically induced colitis, PAT1-deficient mice were significantly more affected by intestinal inflammation than their wild-type counterparts. These mice showed more pronounced symptoms such as weight loss, severe tissue damage and increased inflammatory reactions.
Another key finding of the study is that PAT1 deficiency leads to microbial dysbiosis. PAT1-deficient mice showed a significant decrease in butyrate-producing bacteria and an overall altered composition of the gut microbiome. This dysbiosis correlates with increased intestinal permeability and susceptibility to inflammatory processes.
The study results show that the loss of PAT1 leads to a reduced expression of tight junction proteins, which are the most important determinants of paracellular permeability. At the same time, increased levels of the pro-inflammatory protein claudin-2 were detected, which further increases the permeability of the intestinal wall. These and other changes in protein expression can significantly contribute to the development and worsening of intestinal inflammation.
The present research results underscore the central role of the anion transporter PAT1 in maintaining the intestinal barrier and preventing intestinal inflammation. The loss of this transporter leads to a disturbed microbiome, increased intestinal permeability and increased susceptibility to inflammatory bowel disease. These findings could open up new therapeutic approaches for the treatment of inflammatory bowel disease, particularly by targeting the PAT1 signalling pathway and the gut microbiome. However, further studies are needed to evaluate the translational possibilities of these findings in clinical practice.