Protective impacts of berberine in weaned piglets fed without zinc oxide: Insight of jejunal barrier function, water absorption, and gut microbiota and metabolism

Weaning stress may impact the small intestine, altering its structure and function and lowering its ability to digest and absorb nutrients, weakening intestinal barrier integrity, and resulting in lower feed intake, increased diarrhea, and growth retardation. Berberine is extensively utilized for the treatment of infectious diarrhea due to its potent antibacterial and antipyretic properties. This research seeks to explore how berberine might influence growth performance, diarrhea incidence, jejunal morphology, jejunal microbiota and metabolism, and jejunal gene expression in weaned piglets. A total of 90 weaned piglets, aged 28 days at the outset of the study, were selected and randomly assigned to one of three treatment groups, each comprising six replicates with five piglets per replicate. The experiment was carried out in two phases over 28 days. Piglets received a basal diet (CON) or a diet enhanced with 1600 mg/kg zinc oxide for days 0 to 14, 110 mg/kg zinc oxide for days 15 to 28 (ZIN), and 50 mg/kg berberine throughout days 0 to 28 (XBJ). Compared with CON, dietary berberine significantly improved average daily weight gain (ADG; <i>P</i> = 0.024) and average daily feed intake (ADFI; <i>P</i> = 0.020) in weaned piglets, while reducing the diarrhea index (<i>P</i> = 0.003) at days 0 to 28. Compared with CON, berberine notably enhanced jejunal villus height (<i>P</i> = 0.026), improved the villus height/crypt depth ratio (<i>P</i> = 0.002), increased goblet cell numbers (<i>P</i> = 0.023), and reduced crypt depth (<i>P</i> = 0.022). Compared with CON, berberine notably increased the mRNA relative expression levels of <i>TJP1</i> (<i>P</i> = 0.031), <i>MUC2</i> (<i>P</i> = 0.045), <i>AQP1</i> (<i>P</i> = 0.019), <i>AQP8</i> (<i>P</i> < 0.001), <i>AQP10</i> (<i>P</i> = 0.018) and <i>AQP11</i> (<i>P</i> = 0.004), as well as <i>SLC9A3</i> (<i>P</i> < 0.001) and <i>SLC12A2</i> (<i>P</i> = 0.018) in the jejunum. Berberine notably suppressed the weaning-induced elevation of <i>IL1B</i> (<i>P</i> = 0.017) and <i>RELA</i> (<i>P</i> = 0.029) in the jejunum compared with CON. Dietary berberine administration increased the relative abundance of Bacteroidota (<i>P</i> = 0.063), <i>norank_f__norank_o__Gastranaerophilales</i> (<i>P</i> = 0.022), <i>norank_f__norank_o__RF39</i> (<i>P</i> = 0.063), and <i>norank_f__norank_o__Clostridia_UCG-014</i> (<i>P</i> = 0.064), as well as enhanced acetic acid content (<i>P</i> = 0.062) when compared to CON. Spearman correlation indicated a positive correlation between the relative abundance of <i>norank_f__norank_o__Gastranaerophilales</i> and butyric acid content (<i>P</i> = 0.038), villus height (<i>P</i> = 0.035), the mRNA relative expression levels of <i>OCLN</i> (<i>P</i> = 0.005), <i>AQP8</i> (<i>P</i> = 0.027), <i>TJP1</i> (<i>P</i> = 0.028), and <i>SLC9A3</i> (<i>P</i> = 0.022). Additionally, the relative abundance of <i>norank_f__norank_o__RF39</i> was positively correlated with ADFI (<i>P</i> = 0.038), the mRNA relative expression levels of <i>AQP8</i> (<i>P</i> = 0.004), <i>SLC12A2</i> (<i>P</i> = 0.025), and <i>SLC9A3</i> (<i>P</i> = 0.038). Goblet cells number (<i>P</i> = 0.034), the mRNA relative expression levels of <i>AQP8</i> (<i>P</i> = 0.001), <i>AQP10</i> (<i>P</i> = 0.022), <i>SLC12A2</i> (<i>P</i> = 0.020), and <i>MUC2</i> (<i>P</i> = 0.023) showed a positive correlation with the relative abundance of <i>norank_f__norank_o__Clostridia_UCG-014</i>. The transcriptomic analysis further corroborated that basal diet +50 mg/kg berberine regulates gene expression and functional pathways related to intestinal nutrient absorption and immunity. Berberine in zinc oxide-free diets improved weaned piglets' growth and reduced weaning-related intestinal damage.