Indole-3-propionic acid (IPA)

Indole-3-propionic acid (IPA) is a compound your gut microbes make from dietary tryptophan. Almost only one strict anaerobe, Clostridium sporogenes, produces it, by converting tryptophan in two steps. IPA works through two nuclear receptors. One is the pregnane X receptor (PXR), in your gut lining and liver. The other is the aryl hydrocarbon receptor (AhR). IPA also acts directly, as a free-radical scavenger. Switching on PXR boosts tight-junction proteins (claudin-1, occludin, ZO-1) and mucus proteins (MUC2, MUC4). It also lowers TNF-α and IL-6, by blocking NF-κB. Venkatesh et al. (2014, Immunity) showed this in a mouse colitis model. Li et al. (2021, J Agric Food Chem) confirmed that IPA strengthened the gut barrier and cut leaky flow between cells. The metabolic link comes from the Finnish Diabetes Prevention Study (n = 200). Tuomainen et al. (2018, Nutrition & Diabetes) found that higher blood IPA at one year predicted less type 2 diabetes over 7 years, and better-preserved insulin secretion. IPA also tracked inversely with IL-6 and hsCRP. In aged animals, IPA improved grip strength and bone structure in mice, and extended lifespan in fruit flies, in a sex- and genotype-dependent way (GeroScience, 2025). Your IPA levels respond to diet. Tryptophan intake, prebiotic fiber, and antibiotics all change them. But there are no human intervention trials yet. The evidence is observational or mechanistic, so cause is not established.

Last reviewed: June 22, 2026

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