The road to health is paved with good intestines

The road to health is paved with good intestines

By: Cassidy Myhre

In the same way our senses take clues from the environment to create physiological responses, the cues about the bacterial environment inside our intestines are also influenced by many different senses. Gut microbes communicate to organs and influence host physiology in many ways, including regulating insulin trafficking.

A recent study reveals the direct communication of the gut microbiota by discovering how Nod1 ligand-elicited signaling in the pancreatic beta cells is a mechanism to counterbalance the increased insulin demand associated with elevated levels of microbial products upon colonization. The study also found:

  • Insulin content was reduced in islets of germ-free (GF) mice that have no microbiome.
  • In beta cells lacking Nod1, insulin and proinsulin vesicles were co-localized around the nucleus, much like in GF mice. 
  • The presence of Rab1, Nod1 and Rip2 are all necessary for proper cellular localization of the insulin vesicle and optimal insulin release upon glucose stimulation.

While the physiological explanation for this microbiota-insulin interaction remains puzzling, supporting research of this idea finds that direct activation of NOD1 protein causes insulin resistance, which supports the fact that the absence or depletion of gut microbiota increases insulin sensitivity, especially in fat. 

Other Pathways

Another way the intestinal microbiota has an impact on key physiological host functions is through the essential aromatic amino acid tryptophan (Trp). In the gut, Trp metabolism pathways are under the direct or indirect control of the microbiota. A study on the role of Trp metabolism in microbiota-host crosstalk shows: 

  • Signaling of AhR, a Trp derivative, is considered a key component of the immune response at barrier sites.
  • Oxidative and reductive pathways have been described as leading to the production of indoleacetic acid (IAA) and indolepropionic acid (IPA), two Trp metabolites known to affect intestinal permeability and host immunity. 

What’s next? Insulin resistance is one of the main predictors for T1D, making it very important to understand the mechanisms of specific immune receptors. Further investigation of the complex interactions is needed in order to discover how this communication can contribute to host physiology and how incorrect signaling might contribute to many different diseases.