Indole-3-propionic acid enhances glycolytic myofiber formation in piglets through PI3K-mTOR activation and gut microbiota-driven tryptophan metabolic alteration.

Indole-3-propionic acid (IPA) is a metabolite of tryptophan produced by gut bacterial catabolism that has a variety of functions, including anti-inflammatory, free radical scavenging, and regulation of glucose metabolism. The present study evaluated the effects of dietary IPA supplementation on early muscle development in piglets. Twelve healthy Landrace × Rongchang piglets at 30 d of age were randomly divided into control (CON group, 10.78 ± 0.040 kg) and 0.01% IPA (IPA group, 10.80 ± 0.062 kg) for 50 d. The results showed that IPA increased the proportion of glycolytic myofibers significantly in muscle (P = 0.002). Supplementation with IPA increased pyruvate kinase (PK) activity (P = 0.025) and gene expression of myosin heavy chain 4 (MYH4) in muscle (P < 0.001), and decreased the gene expression of MYH7 and MYH2 (P < 0.01) and mitochondrial respiratory chain complexes (P < 0.01). Supplementation with IPA enhanced insulin sensitivity and activated phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway in vivo and accelerated differentiation of C2C12 cells in vitro. In addition, IPA affected gut microbiota by increasing the Firmicutes-to-Bacteroidetes ratio and significantly reduced the concentration of kynurenine and melatonin (P < 0.05). In conclusion, IPA increased glycolytic myofibers and promoted muscle growth by regulating the homeostasis of glucose metabolism mediated by PI3K-mTOR signaling and the gut microbiota in piglets.