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Saccharomyces cerevisiae (S. cerevisiae) and glucagon-like peptide-2 (GLP-2) have been employed to improve the intestinal development of weaned animals. The goal of this study was to determine whether either exogenous S. cerevisiae or GLP-2 elicits major effects on fecal microbiotas and cytokine responses in weaned piglets. Ninety-six piglets weaned at 26 days were assigned to one of four groups: 1) Basal diet (Control), 2) empty vector-harboring S. cerevisiae (EV-SC), 3) GLP-2-expressing S. cerevisiae (GLP2-SC), and 4) recombinant human GLP-2 (rh-GLP2). At the start of the post-weaning period (day 0), and at day 28, fecal samples were collected to assess the bacterial communities via sequencing the V1-V2 region of the 16SrRNA gene, and piglets’ blood was also sampled to measure cytokine responses (i.e., IL-1β, TNF-α, and IFN-γ). This study revealed that, on the one hand, although S. cerevisiae supplementation did not significantly alter the growth of weaned piglets, it induced increases in the relative abundances of two core genera (Ruminococcaceae_norank and Erysipelotrichaceae_norank) and decreases in the relative abundances of two other core genera (Lachnospiraceae_norank and Clostridiale_norank) and cytokine levels (IL-1β and TNF-α) (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). On the other hand, GLP-2 supplementation had no significant influence on fecal bacterial communities and cytokine levels, but it produced better body weight and average daily gain (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). Therefore, altered fecal microbiotas and cytokine response effects in weaned piglets were due to S. cerevisiae rather than GLP-2.

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