Transcriptomic and Metabolomic Changes Reveal the Immunomodulatory Function of Casein Phosphopeptide-Selenium Chelate in Beagle Dogs.

Casein phosphopeptide-selenium chelate (CPP-Se) is an organic compound produced by the chelation of casein phosphopeptide with selenium. This compound showed the ability to modulate canine immune response in our previous study; but its effect on the peripheral blood transcriptome and serum metabolome was unknown. This study aims to reveal the potential mechanism behind the immunomodulatory function of CPP-Se. We have identified 341 differentially expressed genes (DEGs) in CPP-Se groups as compared to the control group which comprised 110 up-regulated and 231 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis found that DEGs were mainly involved in immune-related signaling pathways. Moreover, the immune-related DEGs and hub genes were identified. Similarly, metabolomics identified 53 differentially expressed metabolites (DEMs) in the CPP-Se group, of which 17 were up-regulated and 36 were down-regulated. The pathways mainly enriched by DEMs were primary bile acid biosynthesis, tryptophan metabolism, and other amino acids metabolic pathways. Combined analysis of transcriptomic and metabolomic data showed that the DEGs and DEMs were commonly enriched in fatty acid biosynthesis, pyrimidine metabolism, glutathione metabolism, and glycerolipid metabolic pathways. Taken together, our findings provided a theoretical basis for further understanding of the immunomodulatory function of CPP-Se as well as a scientific reference for the future use of CPP-Se in pet foods as a dietary supplement to modulate the immunity.

Dextran-Sulfate-Sodium-Induced Colitis-Ameliorating Effect of Aqueous Phyllanthus emblica L. Extract through Regulating Colonic Cell Gene Expression and Gut Microbiomes.

The anti-inflammation effect of aqueous Phyllanthus emblica L. extract (APE) and its possible underlying mechanism in dextran sulfate sodium (DSS)-induced mice chronic colonic inflammation were studied. APE treatment significantly improved the colitic symptoms, including ameliorating the shortening of the colon, increasing the DSS-induced body weight loss, reducing the disease activity index, and reversing the condition of colon tissue damage of mucus lost and goblet cell reduction. Overproduction of serum pro-inflammatory cytokines were suppressed by the treatment of APE. Gut microbiome analysis showed that APE remodeled the structure of gut bacteria in phylum and genus levels, upregulating the abundance of phylum Bacteroidetes, family Muribaculaceae, and genus Bacteroides and downregulating the abundance of phylum Firmicutes. The reshaped gut microbiome caused metabolic functions and pathway change with enhanced queuosine biosynthesis and reduced polyamine synthesis pathway. Colon tissue transcriptome analysis further elucidated APE-inhibited mitogen-activated protein kinase (MAPK), cytokine-cytokine receptor interaction, and tumor necrosis factor (TNF) signaling pathways and the expressions of the genes that promote the progress of colorectal cancer. It turned out that APE reshaped the gut microbiome and inhibited MAPK, cytokine-cytokine receptor interaction, and TNF signaling pathways as well as the colorectal-cancer-related genes to exert its colitis protective effect.

Effects of Casein Phosphopeptide-Selenium Complex on the Immune Functions in Beagle Dogs.

The health of pets is becoming a growing concern for the pet industry and its owners. Immunity is one of the foundational supports for health, thus developing a functional bioactive substance that can boost pets' immunity is essential. Many studies have shown that casein phosphopeptide (CPP) and selenium (Se) can individually regulate immunity in many species, but there has been no reported research on the immunomodulatory function of casein phosphopeptide-selenium complex (CPP-Se). The objective of this study was to investigate the function of CPP-Se on immunomodulation in dogs. Twenty Beagle dogs were equally divided into two groups and fed either a control snack or a test snack supplemented with 0.03% CPP-Se for 30 days. Anticoagulated blood, serum and peripheral blood lymphocytes (PBL) were collected from dogs at 0 d, 10 d, 20 d and 30 d to detect the change in the number of immune cells and the expression of cytokine-related mRNAs and proteins. PBL isolated from blood were exposed to CPP-Se in vitro to measure the proliferative responses and cytokine-related mRNAs expression. During the time the test snack was fed, the number of lymphocytes increased significantly, whereas neutrophils and monocytes remained unaltered. The expression of interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), CD4 molecule (CD4) and CD8α molecule (CD8α) was up-regulated, while interleukin-1ß (IL-1ß) was down-regulated, and interleukin-10 (IL-10) declined initially and subsequently increased. ELISA detection revealed a significant increment in serum IL-4, IL-6, Immunoglobulin M (IgM) and IFN-γ, except for IgG. Furthermore, CPP-Se treatment increased the proliferation and the expression of cytokine-related mRNAs in PBL cultured in vitro. This is the first study to demonstrate that CPP-Se can improve immunity in the dog.