Michel · Neurogastroenterology and motility 2022 · cross-sectional histological morphometric study · n=?

How big is the little brain in the gut? Neuronal numbers in the enteric nervous system of mice, Guinea pig, and human.

Cited 41 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Bench and post-mortem/tissue histological quantification across animal models and human specimens.

PubMed 35929768 · doi:10.1111/nmo.14440 · record verified 2026-08-29

What was done

Standardized tissue preparation and immunohistochemistry using panneuronal markers (human or mouse anti-HuD/C) were used to determine neuronal densities across the entire gastrointestinal tract in mice, guinea pigs, and humans (examining both myenteric and submucous plexuses). Gastrointestinal tract dimensions were directly measured in mice and guinea pigs, whereas human organ dimensions were taken from published literature, to calculate total enteric nervous system (ENS) neuron numbers.

What was found

Average neuronal densities along the gastrointestinal tract were: - Mice: 35,011 ± 25,017 /cm² (myenteric plexus) and 16,685 ± 9,098 /cm² (submucous plexus). - Guinea pigs: 24,315 ± 16,627 /cm² (myenteric plexus) and 11,850 ± 6,122 /cm² (submucous plexus). - Humans: 21,698 ± 9,492 /cm² (myenteric plexus) and 16,367 ± 5,655 /cm² (submucous plexus). Total calculated ENS neuron numbers were 2.6 million for mice, 14.6 million for guinea pigs, and 168 million for humans. Total enteric neuron counts were noted to be comparable to spinal cord neuron counts across all three species.

Why it matters

This study replaces long-standing anecdotal estimates with standardized, empirical neuron counts across species, showing that neuronal densities are relatively conserved and that differences in total enteric neuron counts primarily reflect gastrointestinal dimensions.

Limits

The abstract does not state sample sizes (n) for any species or specify donor demographic characteristics for human tissue. Total human neuron calculations rely on secondary literature estimates of gastrointestinal surface area rather than direct measurements from the sampled donors. Large standard deviations also indicate substantial regional variation across the gastrointestinal tract.

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