Dietary nucleotide-rich yeast extract regulates growth performance, microbiota composition and inflammatory response to lipopolysaccharide challenge in weanling pigs.

A total of 128 weanling pigs (initial body weight, 7.5 ± 0.79 kg) were used to evaluate the effects of nucleotide (NUCL) supplementation to an adequate or low crude protein (CP) diet on growth performance, nutrient digestibility, gut microbiota composition, metabolic and inflammatory response to lipopolysaccharide (LPS) challenge. Pigs were randomly assigned to 4 dietary treatments (n = 8 replicates) in a 2 × 2 factorial arrangement of dietary CP level [adequate protein (AD) or low protein (LP)] and NUCL supplementation (0 or 9 g/kg) for a 42-d trial. The experimental diets were AD without NUCL (AD0), AD with NUCL (AD9), LP without NUCL (LOW0), and LP with NUCL (LOW9). Fecal samples were collected on d 39, 40 and 41 to determine the apparent total tract digestibility (ATTD) of nutrients. On d 42, fresh fecal samples were collected for microbiome analysis, and two pigs per pen were intraperitoneally injected with either saline or LPS (LPS; 25 µg/kg BW). Rectal temperature (RT) was recorded post-challenge, and blood samples were collected for serum analysis. Pigs fed AD diets had higher overall ADG (P < 0.01), G:F and final BW (P < 0.001) compared to LP pigs. Nucleotide supplementation increased (P < 0.05) ADG from d 28-42, final BW, and overall G:F. A significant (P < 0.01) NUCL × CP interaction was observed for d 0 to 14 ADFI which was higher in pigs fed AD9 compared to AD0, but was not different between LOW9 and LOW0 pigs. Nucleotide supplementation also increased (P < 0.01) ATTD of dry matter (DM) and gross energy (GE), while feeding low CP diets tended (P = 0.07) to increase ATTD of nitrogen compared to AD. Low CP diets had lower (P < 0.05) RT at 0 and 4 h compared to AD, while NUCL supplementation decreased (P < 0.05) RT at 4 h post-challenge compared to unsupplemented diets. A NUCL × CP (P < 0.001) interaction was found with serum tumor necrosis factor-alpha (TNF-α) which was lower in LOW9 pigs compared to LOW0, but not different in AD pigs regardless of NUCL supplementation. Both alpha and beta diversities were affected (P < 0.05) by dietary CP level, but not NUCL supplementation. Differential abundance analysis also showed that significant shifts in microbial community structure were primarily associated with dietary CP level. Collectively, these findings suggest that NUCL supplementation influences feed intake during the early post-weaning period, supports immune resilience, and modulates inflammatory responses in a dietary CP-dependent manner.