A Low Dose of Berberine Is Metabolized in Weaned Piglets Without Major Changes to Gut Morphology or Gut Microbiota

Weaning is one of the most challenging stages in a piglet’s life, with multiple stressors contributing to poor gut health. For several years, zinc oxide (ZnO) was the preferred means of promoting a healthy gut and preventing post-weaning diarrhea (PWD). However, with the banning of its use at medicinal levels in the EU since 2022, alternatives are needed. Berberine (BBR), an isoquinoline alkaloid, has been used for centuries in Chinese medicine to treat diarrhea and has pharmacological properties that could make this molecule an attractive alternative to ZnO. The aim of this study was to investigate how berberine is metabolized in the intestinal tract and liver of weaned piglets; determine which metabolites are detected in intestinal contents and plasma; and whether a low dose can alter histomorphological parameters, short-chain fatty acid (SCFA) production, and gut microbiota composition. A total of 60 piglets weaned at 4 weeks were divided into two groups (Control and BBR), each consisting of six pens of five animals. After two weeks of feeding with a normal diet or a berberine-supplemented diet (30 mg berberine/kg feed), berberine and its metabolites were quantified in intestinal contents and plasma by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) on 12 animals per group (2 male piglets per pen). Moreover, villus length and crypt depth were measured in small-intestinal tissue, and 16S rRNA gene sequencing was performed to examine jejunal, cecal, and colonic gut microbiota composition. Our findings show that piglets metabolize berberine into phase I and II metabolites; however, a low dose does not affect their histomorphology, microbiota composition, or SCFA production.