While often called the "second brain," the gut's enteric nervous system truly operates independently in regulating blood sugar, as demonstrated by researchers at Rockefeller University. This finding aligns with established expertise in gut neuroscience.
The enteric nervous system (ENS) in the gut contains as many neurons as the spinal cord, influencing immunity, motility, and hormone regulation. Experts have long noted correlations between gut microbiota diversity and blood sugar variations, but causality remained unproven.
A landmark study published in Science on August 27, 2020, by Rockefeller University scientists established a microbiota-dependent mechanism for glucose and insulin regulation through rigorous mouse experiments.
Researchers employed the RiboTag technique on transgenic mice engineered to express a specific protein tag in translating neurons. This enabled isolation of neuronal messenger RNAs via immunoprecipitation and sequencing, pinpointing microbiota-driven changes.
Microbiota depletion altered the colonic transcriptome, boosting expression of metabolites like the neuropeptide CART (Cocaine- and Amphetamine-Regulated Transcript). Known for hypothalamic roles in appetite and reward, gut-derived CART intrigued the team.
Using retrograde viral tracing, scientists mapped CART neurons from the gut to the superior mesenteric ganglion, which links to the pancreas and liver via sympathetic nerves.
Optogenetic tools with a modified receptor activated by Clozapine-N-oxide allowed precise control of CART neurons. Activation reduced food intake, raised blood glucose, and lowered insulin; deactivation reversed these, disrupting gluconeogenesis—the pathway producing glucose from non-carbohydrate sources.
In essence, microbiota triggers ENS CART secretion, independently modulating liver and pancreas function without central nervous system input. This breakthrough opens avenues for targeting CART pathways in diabetes and obesity management.
