In conclusion, lysozyme supplementation also shifted the metabolic functions and phenotypes of sows gut microbiota. Lysozyme is an important modulator in innate immunity and plays a crucial role in preventing intestinal inflammation (Long et al., 2016;Patel and Kuyucak, 2017;Ragland et al., 2017). to beneficial composition identified by reduced richness ofEscherichia coliand increased large quantity ofLactobacillus amylovorus. Accordingly, microbial metabolic functions includingpyrimidine metabolism, purine metabolism, andamino acid related enzymeswere significantly up-regulated in 1.0 kg/t group. Microbial metabolic phenotypes like the richness of Gram-positive bacteria and oxidative stress tolerance were also significantly reduced by lysozyme treatment. Serum alanine transaminase (ALT) activity and Rabbit Polyclonal to MN1 IgA levels were significantly down-regulated in the 1.0 kg/t group compared with control, but IgM levels showed a significantly increase in 1.0 kg/t group. Milk metabolites such asL-glutamine, creatine, andL-arginine showed significantly dose-dependent changes after treatment. Overall, lysozyme supplementation could effectively improve the composition, metabolic functions, and phenotypes of sows gut microbiota and it also benefit sows with better serum immunity and milk composition. This research could provide theoretical support for further application of lysozyme in promoting animal gut health RETRA hydrochloride and prevent pathogenic infections in livestock production. Keywords:milk, gut microbiota, lysozyme, metabolome, serum immunity == Introduction == Enteric infections caused by pathogens, like EnterotoxigenicEscherichia coli(ETEC), have a significant unfavorable effect on neonatal survival and animal health in swine production (Oliver and Wells, 2013;Wells et al., 2015;Huang et al., 2018). Animal infants infected by pathogenic bacteria often suffer from prolonged diarrhea and severe inflammation (Huang et al., 2018;York, 2018). Continuous inflammation of the intestinal tract prospects to substantial destruction of the intestinal epithelia, resulting in malnutrition and impairing the early growth of infants (Zhao et al., 2012;Zhang et al., 2016;Patel and Kuyucak, 2017). Application of antibiotics in formula feed is well established method and can improve growth rates of piglets (Thymann et al., 2007). However, abuse of antibiotics is usually contributing to the high level of drug resistance in microbial communities and rising issues regarding human health (Zhao et al., 2012;Oliver and Wells, 2013;Long et al., 2016;Oh et al., 2016). An alternative to antibiotics is usually lysozyme, an enzyme and natural broad-spectrum bactericide generally found in tears, saliva, and milk, and that is a vitally important immune system activator under physiological conditions (Maga et al., 2006a,2012;Lee et al., 2009). During bacterial infection of the intestine, RETRA hydrochloride mammalian Paneth cells are also able to secrete lysozyme via secretory autophagy to maintain intestinal homeostasis (Bel et al., 2017). Breast milk contains lysozyme (<0.065 g/mL), along with lactoferrin and secretory IgA (SIgA), which greatly aid the establishment of beneficial gut microbiota in newborns (Maga et al., 2012;Oliver and Wells, 2015). Lysozyme functions by cleaving the -1,4-glycosidic bond betweenN-acetylmuramic acid andN-acetylglucosamine residues of the bacterial peptidoglycan, causing a loss of cellular membrane integrity and cell lysis (Oliver and Wells, 2013;Long et al., 2016). Lysozyme was reported to be more effective against Gram-positive bacteria (Masschalck and Michiels, 2003;Touch et al., 2003;Gao et al., 2017), and it may also indirectly impact several Gram-negative bacterial species (Maga et al., 2006a,b). Previous studies revealed that lysozyme promotes the beneficial microbe community and reduces detrimental microbes within gut microbial communities (Ko et al., 2009;Maga et al., 2012). Lysozyme could be effective against a wide range of gastrointestinal pathogens, such asListeria monocytogenes, Clostridium perfringens, Candidaspp., andHelicobacter pylori in vitro(Brundige et al., 2008;Zhang et al., RETRA hydrochloride 2016). Bacterial sensitivity to lysozyme is also due to the activation of innate components of the immune system, such as increased neutrophil activation during inflammation (Ragland et al., 2017;Huang et al., 2018). It has been reported that lysozyme may possess an anti-inflammatory effect via inhibiting JNK phosphorylation (Tagashira et al., 2018). Furthermore, lysozyme is usually capable of enhancing intestinal SIgA secretion, cause macrophage activation, and promote quick clearance of bacterial pathogens (Lee et al., 2009;Wells et al., 2015;Ragland et al., 2017). Recent studies reported that lysozyme sourced from chicken eggs showed significant improvements in improving growth overall performance, intestinal morphology, gut microbiota composition, and immunity of piglets (May et al., 2012;Oliver and Wells, 2013,2015;Oliver et al., 2014;Wells et al., 2015). For instance, weaned piglets received a hen-egg white lysozyme treatment shown better intestinal growth and development, as well as decreased ETEC counts around the intestinal mucosa and serum proinflammatory cytokines (Nyachoti et al., 2012). Moreover, lysozyme produced by transgenic animals and structurally altered lysozyme was shown to possess significant antimicrobial properties against pathogens like ETEC in piglets (Nattress and Baker, 2003;Maga et al., 2006a;Brundige et al., 2008;Tong et al., 2011;Nyachoti et al., 2012;Lu et al., 2015). Piglets that consumed lysozyme-transgenic goats milk (containing human lysozyme at 67% of the concentration in human breast milk) showed better intestinal morphology and fewer total coliform counts (Brundige et al., 2008). Gut microbiota plays multiple functions in animal growth and health, including energy extraction from the diet, gut barrier function and immunity as well as growth overall performance.