The gut microbiota-enteric nervous system axis: from bidirectional programming to precision therapeutics in digestive...

Area of Science:

• Gastroenterology and Neuroscience
• Microbiome Research
• Gut-Brain Axis Studies

Background:

• The gut microbiota (GM) and enteric nervous system (ENS) engage in vital bidirectional communication essential for gastrointestinal homeostasis.
• This interaction evolves from a developmental role in early life to regulating neural plasticity in adulthood.

Purpose of the Study:

• To dissect the complex GM-ENS dialogue and its signaling mechanisms.
• To propose a multi-timescale model of GM-ENS communication relevant to digestive diseases.
• To explore the GM-ENS axis's role in pathophysiology and therapeutic development.

Main Methods:

• Literature review synthesizing current knowledge on GM-ENS signaling.
• Development of a multi-timescale model (rapid, intermediate, slow) for GM-ENS interactions.
• Analysis of the GM-ENS axis's role in Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), and Colorectal Cancer (CRC).

Main Results:

• Core signaling mechanisms include microbial metabolites, neuroactive substances, and immune mediators.
• A multi-timescale model highlights differential relevance for IBS (fast distortions) and IBD (slow amplification).
• The GM-ENS axis acts as a "signal distorter" in IBS, "inflammation amplifier" in IBD, and "tumor accomplice" in CRC.

Conclusions:

• The GM-ENS axis is central to understanding digestive disease pathogenesis.
• Emerging therapeutic strategies targeting this axis include precision biomarkers, synthetic microbial consortia, and postbiotics.
• The GM-ENS axis offers a promising framework for next-generation precision medicine in gastroenterology.