Sodium butyrate enhances feed utilization and average daily gain in calves before weaning
Several studies reported that dietary supplementation with SB could enhance animal growth and stimulate the growth of duodenal mucosa in broiler chickens, stimulate growth performance and feed intake in young pigs, especially before weaning , enhance the development of jejunal and ileal mucosa in formula-fed piglets , and improve the growth performance of young calves . The positive effects of supplementation of milk and/or MR with SB on the growth parameters observed in our study corroborate the previous studies and support the notion that butyrate supplementation is more effective when fed dairy calves earlier rather than later [14, 30]. In newborn calves, solid feed intake depends on the development of the rumen, including the rumen tissue, rumen papillae, and the rumen microbiome [32, 33]. In the present study, we did not see any increase in feed intake by SB supplementation. This is consistent with the reports by Hill et al.  and Vazquez-Mendoza et al. . The supplementation with SB did increase ADG, which concurs with the improved ADG previously observed in weaned calves supplemented with SB [22, 35]. There was a linear trend in reducing the F:G ratio as SB levels increased, and SB supplementation at 15 g/d decreased the F:G ratio by nearly 14% throughout the feeding trial. Several studies have reported different modes of action of SB supplementation in young animals. One study suggested that butyrate might enhance growth performance in young calves by improved feed digestibility , while another study proposed that butyrate might enhance the absorption capacity of nutrients by increasing the depth of the crypts and the length of small intestine villi, thus increasing the absorptive surface area, in rats and pigs . In newborn calves, SB was shown to stimulate the development of the rumen  and small intestines  and enhance the maturation of the intestinal tract (including increased villus size and activities of digestive enzymes) . The mode of action of SB supplementation at work may depend on the growth stage of calves. Future wholistic studies are needed to elucidate the underlying mechanisms by integrating transcriptomic and proteomic approaches coupled with morphological and histochemical methodologies to investigate the growth and development of the host, especially the digestive system, and meta-omic approaches to investigate the rumen microbiome.
Sodium butyrate has little effect on rumen fermentation in calves before weaning
Rumen fermentation starts at a very young age in calves, and VFAs can be found in their rumen from the second week of their life . In the rumen, butyrate confers multiple protective benefits, such as improving tight junctions, epithelial energy mobilization, and VFA absorption capacity . Studies have shown that butyric acid could lower the rumen pH of calves , which can promote the GI colonization with beneficial bacteria . However, our study showed that SB did not affect the rumen pH of calves, probably because SB, as a salt of a strong base and a weak acid, could raise rumen pH, and/or most of the SB bypassed the rumen together with the ingested liquid feed. Nevertheless, the rumen pH recorded in the present study should not have any detrimental effects on rumen development. The ruminal VFA concentrations, both total and individual, were not affected by the supplement with SB in this study. However, as demonstrated in other studies [2, 24, 40], SB supplementation might have enhanced the absorption of VFAs in the rumen  and improve the development of the rumen [24, 40]. Further research should investigate the mechanism by which SB enhances VFA of the production and absorption. No effect of SB on the NH3-N concentration was observed in this study, which could reflect the balance of protein degradation and NH3-N uptake by rumen microbes synthesis . More research will need to be done to investigate the effect of SB on nitrogen utilization in calves.
Sodium butyrate enhances the serum antioxidant capability in calves before weaning
Calving leads to oxidative stress, which can increase the formation of reactive oxygen species (ROS) and overwhelm the antioxidant systems of calves . Reactive oxygen species, and reactive nitrogen species to a lesser extent, can cause oxidative damages to tissues and overwhelm the body's endogenous antioxidant capacity . The antioxidative enzymes, such as SOD, GSH-Px, and CAT , are essential components of oxidative stress defense systems in animals. In the present study, we evaluated how SB might affect oxidative stress and the oxidative stress defense system. Compared to that of the control group, the GSH-Px activity increased with increasing SB levels, while the serum MDA concentration decreased linearly. A previous study showed that dietary SB increased the activity of SOD and decreased serum MDA concentration in chicken . Using an IPEC-J2 cell model of piglets, Ma et al.  showed that alteration to the antioxidant system by SB could suggest an attenuation of oxidative stress in the intestinal mucosa. Butyrate has also been shown to decrease the oxidative damages to human colorectal cells , reduce oxidative stress precipitated by colonic inflammation caused by cancer-induced destruction of the intestinal barrier , and alleviate oxidative stress induced by lipopolysaccharides in intestinal epithelial Caco-2 cells and colonic mucosa  and streptozotocin diabetic rats . The discrepancies between our study and the above studies with respect to the activity of SOD may be attributable to differences in the levels of SB and animals used. Nevertheless, the increased GSH-Px activity and decreased MDA concentration among the calves supplemented with SB demonstrate the benefits of SB supplementation to help the calves in coping with the oxidative stress from which they suffered in their young lives.
Sodium butyrate does not affect serum concentrations of IgA, IgG, or IgM in calves before weaning
As three important antibodies of the immune function of animals including calves, IgA, IgG, and IgM can protect animals and humans against a variety of pathogens and viruses, activate the complement system, regulate the antibody-dependent cell-mediated cytotoxicity, and improve animal's immunity . Butyrate has been found to have a profound impact on the immune system in humans and rodents . Supplementation with SB also increased the number of IgA+ cells, which later increased the production of secretory IgA in the jejunum of piglets  and increased serum IgG concentrations in pigs . In the present study, supplementation of SB in milk and/or MR did not affect the serum concentrations of any of the three antibodies in the calves, which was in accordance with the report that supplementation with SB in acidified milk did not affect the serum immunoglobulin concentration in calves . The discrepancies between our study and the studies on other animal species might be attributable to differences in SB supplementation levels, methods of SB supplementation, and the animal species used. Further research is warranted to further investigate if butyrate modulates immune system development and function in calves using other immunological analyses than just analysis of the three Ig.