Since essential oils—such as cinnamaldehyde, thymol, carvacrol, and eugenol—have antibacterial, antioxidant, and anti-inflammatory properties, this study aimed to examine the supplementation of different essential oil mixtures together with 1600 mg/kg zinc oxide (ZnO) on growth performance, incidence of diarrhea, serum immune indices, fecal volatile fatty acids, and microflora structure in weaned piglets. A total of 240 weaned piglets (Duroc × Landrace × Yorkshire) with an average body weight of 8.85 ± 0.21 kg were randomly allocated to 30 pens (6 pens per diet, 4 males and 4 females per pen). Five different experimental diets were prepared and administered for 28 days: (i) a control diet (C), a corn–soybean basal diet without antibiotics, ZnO, or a supplementation of growth promoters; (ii) a control diet with 400 mg/kg essential oil mixtures 1 (EOM1); (iii) a control diet supplemented with ZnO at 1600 mg/kg (Z); (iv) a diet incorporating the Z diet with the addition of essential oil mixtures 1 at 400 mg/kg (ZOM1); and (v) a diet incorporating the Z diet with the addition of essential oil mixtures 2 at 400 mg/kg (ZOM2). During day (d) 14–28 and d 1–28 of the experiment, the average daily gain (ADG) in piglets in the ZOM1 and ZOM2 groups were higher (p < 0.05) compared to the C group. The diarrhea incidence of the Z, ZOM1, and ZOM2 groups were significantly decreased (p < 0.05), and the piglets of the ZOM1 group exhibited the lowest diarrhea incidence throughout the trial period. Additionally, the apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF), acid detergent fiber (ADF), ash, organic matter (OM), and ether extract (EE) were higher than those fed the Z diet, and higher levels of NDF, ADF, and crude protein (CP) were observed in groups other than those fed the ZOM1 diet (p < 0.01). On d 14, the pigs fed EOM1 and ZOM2 diets showed a somewhat lower (p < 0.1) immunoglobulin G (lgG) level in serum than those fed the C diet. Additionally, the IL-8 level in serum in the ZOM1 group tended to be higher than that in the other groups (p < 0.1). The piglets fed the ZOM1 diet showed a tendency of lower (p = 0.05) acetate concentration in feces on d 14. Principal co-ordinates analysis (PCoA) showed significant differences (p < 0.05) in the composition of fecal microbial communities among the groups. Dietary EOM1 significantly increased the number of fecal bacteroides (p < 0.05) and tended to increase the number of Prevotella (p < 0.1). Therefore, EOM1 combined with 1600 mg/kg ZnO tends to reduce diarrhea incidence, tends to improve the fecal microbial community structure and growth performance of weaned piglets, and has the potential to replace pharmacological dosages of ZnO.
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