Gut-Brain Axis Interactions and Neurointestinal Mechanisms

The gut–brain axis denotes a complex, bidirectional network through which the central nervous system and the enteric nervous system communicate with the gastrointestinal tract and its resident microbiota. This dialogue is mediated by neural pathways—including the vagus nerve and spinal afferents—endocrine signals such as gut hormones, immune mediators like cytokines, and microbial metabolites including short‐chain fatty acids and tryptophan derivatives. The enteric nervous system, often referred to as the “second brain,” comprises a meshwork of neurons and glia that regulate motility, secretion and barrier function. Microbial communities influence the development, plasticity and homeostasis of these neural circuits from early life onward. Conversely, stress, diet and disease can perturb microbial balance, leading to dysbiosis, altered barrier integrity and aberrant signalling that feed back to central autonomic and limbic centres. Emerging evidence links these neurointestinal interactions to functional gastrointestinal disorders, metabolic disease, neurodevelopmental and neurodegenerative conditions. Understanding the molecular and cellular mechanisms of the gut–brain axis holds promise for novel diagnostics and therapies that harness probiotics, dietary interventions, neuromodulation and postbiotics to restore gut and brain health on a global scale.

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Gut-Brain Axis Interactions and Neurointestinal Mechanisms publication trend

The graph below shows the total number of articles in gut-brain axis interactions and neurointestinal mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Gut-brain axis: The bidirectional communication system linking the gut environment, enteric and central nervous systems via neural, endocrine, immune and metabolic pathways.

Enteric nervous system (ENS): A network of neurons and glial cells within the gut wall that independently governs gastrointestinal motility, secretion and blood flow.

Microbiota: The community of microorganisms, including bacteria, archaea, viruses and fungi, that inhabit the gastrointestinal tract and influence host physiology.

Dysbiosis: A pathological imbalance in microbial composition or function that disrupts normal host–microbe interactions.

Short-chain fatty acids (SCFA): Microbial fermentation products, chiefly acetate, propionate and butyrate, that serve as signalling molecules and energy sources for host tissues.

Lipopolysaccharide (LPS): A component of the outer membrane of Gram-negative bacteria that can modulate immune responses and neuronal survival.

Vagal tone: The level of parasympathetic activity exerted via the vagus nerve, reflecting capacity for autonomic regulation of inflammation and stress responses.

References

1. Gut microbiota depletion delays somatic peripheral nerve development and impairs neuromuscular junction maturation. Gut Microbes (2024).
2. The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System. Gastroenterology (2016).
3. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Frontiers in Neuroscience (2018).