It is now well established that the gut microbiota plays a role in our immunity. However, one question remains: how is the connection made? A recent study including in vitro and in vivo results provides the beginning of an answer.


Our intestine, made up of a layer of epithelial cells, is home to a microbial community that lives in balance. This is the intestinal microbiota. This organ acts as a barrier, allowing the selective passage of molecules into the bloodstream. Nevertheless, some disturbing elements can unbalance this ecosystem. This disrupted balance, named dysbiosis, can lead to intestinal inflammation: the intestinal microbiota is no longer involved in protecting us against pathogens. The possibility of being affected by various pathologies then follows.

An anti-inflammatory protein story

An intestinal protein, P-glycoprotein (P-gp), appears to allow the gut and the immune system to communicate across the gut lining. P-gp is a membrane transporter that:

  • modulates the efflux of toxins and xenobiotics from the mucosa into the intestinal lumen;
  • plays a key role in protecting the intestinal epithelium through its ability to modulate inflammation.

Indeed, P-gp releases anti-inflammatory molecules: endocannabinoids. Thus, in the absence of disease, the protein is highly expressed on the surface of intestinal epithelial cells and exerts an influence in promoting the health of the gut barrier. In contrast, a low concentration of the protein is observed in cases of chronic inflammatory bowel disease (IBD).

How can we encourage its expression?

Based on these findings, scientists sought to determine the role of the gut microbiota in the expression and function of P-gp. Through their work with mice, they have identified bacteria belonging to the genera Clostridia and Bacilli that appear to be capable of this. This bacterial community is known to:

  • produce short-chain fatty acids such as butyrate (a major energy source for the intestinal epithelium);
  • convert primary bile acids into secondary bile acids. The latter contribute to intestinal homeostasis and reduce inflammation.

Butyrate and secondary bile acids are therefore metabolites of the gut microbiota acting together to promote maximum expression of functional P-gp.

Furthermore, in the clinical trial conducted on patients with ulcerative colitis, the researchers were able to confirm a decrease in the P-gp protein in this population, coupled with the reduction of anti-inflammatory endocannabinoids (results given in comparison to healthy people).

Any hope for treatment?

These results confirm the link between the gut microbiota balance, immune system function and gut health.


The regulation of P-gp by intestinal microorganisms raises the possibility of new therapies to treat IBD. It would not be unreasonable that in the future, probiotics capable of increasing P-gp could be proposed to manage this type of pathology.



Picture: Freepik

FOLEY SE, TUOHY C, DUNFORD M, GREY MJ, DE LUCA H, CAWLEY C, SZABADY RL, MALDONADO-CONTRERAS A, HOUGHTON JM, WARD DV, MRSNY RJ, MCCORMICK BA. Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis. Microbiome. 2021, 9(1):183