Simple SummarySupplementing diets with yeast or yeast cultures is recognized as a common practice in modern dairy farming because of the positive effects of yeast on production, health, and immunity performance in ruminants. Recent studies have demonstrated that supplementation with Candida tropicalis has potential benefits by improving fibrous material digestion and antioxidant function, and enhancing the microbial activities in the rumen. Meanwhile, flavonoids, as secondary plant metabolites, are ubiquitously present in plants used for livestock feed, have health-promoting properties, including antioxidative, anti-inflammatory, and metabolic effects. However, in practice, supplementation with monostrain probiotics or individual additives has not enhanced production as expected. Therefore, we hypothesize that multispecies probiotics or the combination of yeast and phytochemicals could be compatible with each other and act synergistically. The results showed that supplementation with C. tropicalis or flavonoids improved rumen fermentation, but supplementation with C. tropicalis had limited effects on increasing growth performance and decreasing fecal scores compared with flavonoid supplementation. However, the combination of C. tropicalis and flavonoids did not show a synergistic effect on health or rumen fermentation compared with use of flavonoids alone in pre- and post-weaning calves.AbstractAlthough flavonoids or yeast have been used as feed additives to improve the production efficiency and health of adult cattle, little information is available on their effects on rumen fermentation in calves. The objective of this study was to investigate the effects of feed supplementation with mulberry leaf flavonoids and Candida tropicalis on performance, blood parameters, and rumen fermentation characteristics during pre-weaning and post-weaning periods. Forty-eight Holstein calves were used in a four-groups trial and were supplemented with (1) no yeast or flavonoids (CON), (2) active dry yeast (ADY; C. tropicalis, 5.0 × 109 CFU/d), (3) flavonoids (FLA; 3 g/d), or (4) yeast and flavonoids (YF; C. tropicalis, 5.0 × 109 CFU/d; flavonoids, 3 g/d). The feeding strategy was as follows: milk replacer was offered at 12% of body weight in two meals per calf each day at age 21 d, and a gradual weaning process was adopted at age 50 to 56 days. Data of daily feed intake, body weight, and serum and rumen fermentation parameters were obtained at 28, 42, 56, and 80 d ages, respectively. A significant time effect and interaction between treatment and time was found for average daily gain, feed efficiency, total volatile fatty acid concentration, and proportion of propionate in calves (p < 0.05). Average daily gain and feed efficiency increased during post-weaning and overall periods for calves in FLA and YF groups compared with CON and ADY groups (p < 0.05). A reduction of fecal scores with supplementation was found in FLA and YF groups (p < 0.05). Rumen fluid pH and ammonia nitrogen concentration remained constant across the groups, ...