De Vadder · Cell 2014 · Animal experimental mechanistic study · n=?

Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits.

Cited 2210 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical animal and bench research with no human clinical data.

PubMed 24412651 · doi:10.1016/j.cell.2013.12.016 · record verified 2026-08-29

What was done

Evaluated the mechanisms by which soluble dietary fiber and microbiota-generated short-chain fatty acids (butyrate and propionate) affect glucose and energy homeostasis in normal mice and mice deficient in intestinal gluconeogenesis (IGN). Assessed signaling pathways including cAMP-dependent mechanisms and FFAR3-mediated gut-brain neural circuits.

What was found

The abstract provides no numerical data. Qualitatively, butyrate stimulated IGN gene expression via a cAMP-dependent pathway, whereas propionate stimulated IGN gene expression through an FFAR3-dependent gut-brain neural circuit. The protective effects of dietary fiber and short-chain fatty acids on body weight and glucose control were abolished in IGN-deficient mice, even though gut microbiota composition shifted similarly to control animals.

Why it matters

It establishes intestinal gluconeogenesis and gut-brain neural signaling as necessary mediators for the metabolic benefits derived from soluble dietary fiber and short-chain fatty acids.

Limits

The study was conducted entirely in mice, limiting direct translation to human physiology. The abstract omits sample sizes, specific fiber or metabolite dosages, durations of exposure, and quantitative effect sizes.

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