Dietary 18β-Glycyrrhetinic Acid Supplementation Improves Intestinal Function and Gut Microbiota in...

Weaning-induced oxidative stress impairs feed intake and compromises intestinal health in piglets. 18β-glycyrrhetinic acid (GA), a bioactive triterpenoid from licorice, has multiple biological effects, but its protective role under oxidative stress in piglets remains unclear.

This study aims to investigate the effects of GA on feed intake, intestinal health, and gut microbiota in weaned piglets exposed to D-galactose (Gal)-induced oxidative stress.

Twenty-four healthy large white piglets (weaned at days 28) were divided into 3 group: 1) Control group (n = 8), basal diet; 2) Gal group (n = 8), basal diet supplemented with Gal (10 g/kg body weight); and 3) GA + Gal group (n = 8), basal diet supplemented with GA (100 mg/kg diet) and Gal (10 g/kg body weight). The study lasted 28 d. At the end of the experiment, serum, hypothalamus tissue, jejunum tissue, ileum tissue, and ileum content were collected for biochemical, molecular, and microbial analyses. One-way analysis of variance followed by Duncan's test was used for data analysis.

Compared with the Gal group, GA supplementation improved the average daily feed intake (Gal: 0.65 ± 0.04 kg, GA + Gal: 0.79 ± 0.06 kg) by 21.54% and average daily gain (Gal: 0.25 ± 0.04 kg, GA + Gal: 0.41 ± 0.06 kg) by 64% from days 14 to 28 (P < 0.05) but had no such effect from d 0 to 14 (P > 0.05), reduced serum malondialdehyde levels (Gal: 2.39 ± 0.23 nmol/mL, GA + Gal: 1.52 ± 0.25 nmol/mL, P < 0.05) and increased glutathione peroxidase activity (Gal: 88.33 ± 6.06 nmol/min/mL, GA + Gal: 115.36 ± 8.15 nmol/min/mL, P < 0.05). GA supplementation enhanced jejunal fluorescence expression of taste receptor type 1 member 2 (Gal: 46.15% ± 2.07%, GA + Gal: 58.53% ± 4.22%) and member 3 (Gal: 22.76% ± 1.80%, GA + Gal: 35.81% ± 2.63%) than those of Gal group (P < 0.05), and dietary GA also markedly increased ileal Romboutsia relative abundance (P < 0.05). Additionally, compared with the Gal group, GA supplementation increased the positive cells of appetite-related genes (Gal: 54.68% ± 3.70%, GA + Gal:80.16% ± 6.56%, and neuropeptide Y (NPY), Gal: 41.06% ± 8.13%, GA + Gal: 75.38% ± 9.45%) in the hypothalamus (P < 0.05), along with elevated serum levels of ghrelin (Gal: 1674.10 ± 97.10 ng/mL, GA + Gal: 2260.41 ± 113.22 ng/mL, P < 0.05) and NPY (Gal: 179.89 ± 6.46 ng/mL, GA + Gal: 200.94 ± 7.88 ng/mL, P < 0.05).

Our findings demonstrate that GA supplementation alleviates oxidative stress, with associated improvements in feed intake and intestinal function, likely mediated through taste receptor signaling, gut microbiota modulation, and hypothalamic appetite regulation. These findings support GA as a potential nutritional strategy to maintain gut health under stress conditions.