By misuse of language, we define the gut as our "second brain". However, US researchers have discovered the independent action of the intestinal nervous system on our blood sugar. For experts, this finding is not so surprising.
The gut has its own nervous system, prompting popularization to call it a "second brain." If this name is not scientific, you should still know that our enteric nervous system has many neurons, that is to say as many as the spinal cord . This plays a role in various functions such as immune function, motor function and hormonal function.
Furthermore, experts in the field already knew that the gut microbiota is statistically correlated to variations in our blood sugar levels . On the other hand, this correlation was not until now considered as a causality. In a study published in the journal Science on August 27, 2020, researchers from Rockefeller University (USA) report on their progress. Scientists have conducted experiments showing that there is at least one microbiota-dependent mechanism acting on the regulation of glucose and insulin.
RiboTag is the name of the methodology put in place by scientists from research on mice. This involved harvesting all the messenger RNAs produced by certain parts of the intestine and being translated (transcriptome) before carrying out sequencing. Beforehand, the leaders of the study designed transgenic mice capable of expressing a small protein sequence (tag) whose purpose will be to express itself in the part of the messenger DNA undergoing translation (exon).
Furthermore, the tag is specific to certain cells – here neurons – which is possible thanks to the tools of genetic engineering. Thus, the cells will express the tag before an antibody specific to this same tag isolates and concentrates the messenger RNAs being translated. This process is called immunoprecipitation.
The study compared mice with or without microbiota. According to the results, the less the microbiota is rich in bacterial species, the more the transcriptome differs. However, these differences are located in particular in regions such as the colon. You should know that the microbiota is at the origin of the expression of metabolites diverse and varied. Among the latter, we find neuropeptides including CART+ (Cocaine and amphetamine regulated transcript).
The CART neuropeptide is no secret to people working in basic research. Indeed, this determines food intake but is also expressed in the hypothalamus , a part of the brain that plays a role in reward and body weight regulation, among other things. However, the fact is that the presence of CART intrigued the researchers and they wanted to understand its source and its purpose.
To do this, the scientists used a modified virus with the aim of infecting CART-secreting neurons. Namely that the neurons have been subjected to a retrograde infection , that is, by returning to their starting point. Thus, the researchers were able to observe that CART neurons leave the intestine towards the viscera, subsequently innervating the superior mesenteric ganglion. However, the latter is connected to the pancreas and the liver via the sympathetic nervous system.
Scientists performed experiments that turned CART neurons on and off. This was possible thanks to a modified receiver can be activated only in the presence of a synthetic ligand. The latter is none other than Clozapine-N-oxide, a synthetic molecule that activates the famous receptor.
When CART neurons are active, a decrease in food intake is observed in mice. We should also mention the presence of an increase in blood sugar and a decrease in insulinemia. In case of deactivation, the reactions are the opposite. Moreover, this deactivation interferes with gluconeogenesis. This is the glucose-generating metabolic pathway from other substrates.
In short, the microbiota induces a secretion of CART neuropeptides via certain neurons of the enteric nervous system. This indirectly innervates the liver and pancreas and generates a glucose-regulatory functionwithout any intervention of the central nervous system. This discovery is not an end in itself and raises many questions that scientists will have to study. Perhaps in the near future, regulating these CART secretions could make it possible to fight certain diseases such as diabetes and obesity.
