Casein hydrolysate supplementation in low-crude protein diets increases feed intake and nitrogen retention without affecting nitrogen utilization of growing pigs.

BACKGROUND: An extreme reduction of the crude protein (CP) level in diets, even balanced with amino acids (AAs), is detrimental for intestinal nitrogen (N) metabolism and the growth of pigs. This study investigated the effects of casein hydrolysate supplementation in low-CP diets on growth performance, N balance, and intestinal N supply for pigs. A total of 24 barrows were randomly assigned to one of three dietary treatments of 160 g kg-1 CP (control), 130 g kg-1 CP (LAA), and 130 g kg-1 CP plus casein hydrolysate (LCH) for 28 days. RESULTS: The LCH group had a higher average daily feed intake (ADFI) and average daily gain (ADG) than the LAA group, and a higher ADG than the control (P < 0.05). Compared with the control, both the LAA and LCH decreased N intake, serum urea N, fecal N, and N excretion, and increased apparent N availability, with LCH having higher N intake and N retention than LAA group (P < 0.05). Compared with LAA, LCH increased ileal fluxes of CP and AA (P < 0.05), and with values similar to those of the control. However, ileal flows of CP and AA were similar between LCH and LAA, both of which were lower than those in the control (P < 0.05). CONCLUSION: Using protein hydrolysate to replace some crystalline AAs in low-CP diets increased feed intake, N retention and ADG without affecting N utilization. These findings point to the important impact of protein hydrolysate supplementation on improving growth for pigs fed low-CP diets. © 2019 Society of Chemical Industry.

Effect of resistant and digestible rice starches on human cytokine and lactate metabolic networks in serum.

Resistant starch generated after treating ordinary starch is of great significance to human health in the countries with overnutrition. However, its functional evaluation in the human body has been rarely reported. By determining the lactate metabolic flux, 12 serum enzymes expression level and 38 serum cytokines in healthy volunteers, the variation in cytokine network and lactate metabolic network in serum were investigated to compare the mechanism of the physiological effects between the two starches. The results indicated that compared with digestible starch, resistant starch had anti-inflammatory effects, increased anabolism, and decreased catabolism. Further, the intercellular communication networks including cytokine and lactate metabolic networks were mapped out. The relationship suggested that resistant starch might affect and control the secretion of cytokines to regulate lactate metabolic network in the body, promoting the development of immunometabolism.

The Disease and Gene Annotations (DGA): an annotation resource for human disease.

Disease and Gene Annotations database (DGA, http://dga.nubic.northwestern.edu) is a collaborative effort aiming to provide a comprehensive and integrative annotation of the human genes in disease network context by integrating computable controlled vocabulary of the Disease Ontology (DO version 3 revision 2510, which has 8043 inherited, developmental and acquired human diseases), NCBI Gene Reference Into Function (GeneRIF) and molecular interaction network (MIN). DGA integrates these resources together using semantic mappings to build an integrative set of disease-to-gene and gene-to-gene relationships with excellent coverage based on current knowledge. DGA is kept current by periodically reparsing DO, GeneRIF, and MINs. DGA provides a user-friendly and interactive web interface system enabling users to efficiently query, download and visualize the DO tree structure and annotations as a tree, a network graph or a tabular list. To facilitate integrative analysis, DGA provides a web service Application Programming Interface for integration with external analytic tools.

Amino acid utilization allows intestinal dominance of Lactobacillus amylovorus.

The mammalian intestine harbors heterogeneous distribution of microbes among which specific taxa (e.g. Lactobacillus) dominate across mammals. Deterministic factors such as nutrient availability and utilization may affect microbial distributions. Due to physiological complexity, mechanisms linking nutrient utilization and the dominance of key taxa remain unclear. Lactobacillus amylovorus is a predominant species in the small intestine of pigs. Employing a pig model, we found that the small intestine was dominated by Lactobacillus and particularly L. amylovorus, and enriched with peptide-bound amino acids (PBAAs), all of which were further boosted after a peptide-rich diet. To investigate the bacterial growth dominance mechanism, a representative strain L. amylovorus S1 was isolated from the small intestine and anaerobically cultured in media with free amino acids or peptides as sole nitrogen sources. L. amylovorus S1 grew preferentially with peptide-rich rather than amino acid-rich substrates, as reflected by enhanced growth and PBAA utilization, and peptide transporter upregulations. Utilization of free amino acids (e.g. methionine, valine, lysine) and expressions of transporters and metabolic enzymes were enhanced simultaneously in peptide-rich substrate. Additionally, lactate was elevated in peptide-rich substrates while acetate in amino acid-rich substrates, indicating distinct metabolic patterns depending on substrate forms. These results suggest that an increased capability of utilizing PBAAs contributes to the dominance of L. amylovorus, indicating amino acid utilization as a deterministic factor affecting intestinal microbial distribution. These findings may provide new insights into the microbe-gut nutrition interplay and guidelines for dietary manipulations toward gut health especially small intestine health.

Low crude protein diets supplemented with casein hydrolysate enhance the intestinal barrier function and decrease the pro-inflammatory cytokine expression in the small intestine of pigs.

To reduce nitrogen excretion and lower feeding costs, low crude protein (CP) diets are sometimes proposed, however, a great reduction of dietary CP concentration (>4% reduction vs. recommended concentration), even supplemented with essential and nonessential amino acids (AA) can detrimentally affect small intestinal barrier function and immunity, possibly due to the excessive lack of peptides. Here we hypothesize that with an extremely low CP concentration diet, protein-derived peptides, rather than AA supplementation, can improve intestinal barrier development and health. To test this hypothesis, 21 growing pigs (19.90 ± 1.00 kg body weight) were randomly assigned to 3 treatments with control diet (16% CP), or low CP diets (13% CP) supplemented with AA (LCPA) or casein hydrolysate (LCPC) for 28 days. In comparison with the control diet, the LCPA diet decreased the protein expression level of jejunal barrier factor zonula occludens-1 (ZO-1) and stem cell proliferation factor leucine-rich repeat-containing G-protein-coupled receptor-5, whereas the LCPC diet enhanced intestinal barrier function by increasing the protein expression level of jejunal occludin and ZO-1 and ileal mucin-2. The LCPA diet reduced Lactobacillus counts, whereas the LCPC diet increased Lactobacillus counts and reduced Escherichia coli counts in the ileum. The LCPA diet also increased protein expression levels of pro-inflammatory cytokine interleukin-6 (IL-6) and IL-22, whereas the LCPC diet decreased protein expression levels of pro-inflammatory IL-1ß, IL-17A and tumor necrosis factor-α in the ileum. Collectively, the casein hydrolysate supplementation of low CP diets showed beneficial effects on the small intestinal barrier, bacterial community, and immunity in pigs, pointing to the important role of protein-derived peptides in small intestinal health in cases of low crude protein diets.

Stimulation of Gastric Transit Function Driven by Hydrolyzed Casein Increases Small Intestinal Carbohydrate Availability and Its Microbial Metabolism.

Gastrointestinal (GI) functions affect gut nutrient flow and microbial metabolism. Dietary peptides modulate GI functions and improve small intestinal health, but the mechanism remains elusive. This study aims to investigate whether dietary peptides affect small intestinal microbial metabolism, and the underlying mechanisms. An ileal-cannulated pig model is adopted to explore the relationship between gut nutrient flow and microbial metabolism after treatment with hydrolyzed casein (peptides) or intact casein (Control)-based diet. The results demonstrate that hydrolyzed casein enhances microbial carbohydrate metabolism with higher Streptococcus abundance and higher lactate level in the ileum. Meanwhile, hydrolyzed casein increases ileal flows of nutrients, especially carbohydrate, leading to a higher carbohydrate availability in ileal digesta. To unveil the mechanisms, it is found that the hydrolyzed casein enhances the ghrelin signal and improves development of interstitial cells of Cajal and muscular layer in gastric corpus, indicating the enhanced upper GI transit function. In addition, hydrolyzed casein improves small intestinal health, as indicated by higher villus heights and luminal lactate concentrations in the jejunum and ileum. In conclusion, hydrolyzed casein stimulates upper GI transit function, enhances gut nutrient flow, and increases small intestinal carbohydrate availability and its microbial metabolism, which favor the small intestinal health.

Baked Bread Enhances the Immune Response and the Catabolism in the Human Body in Comparison with Steamed Bread.

It is unclear whether different processing methods change the biological functions of foods and how these functions are evaluated in the human body. Here, steamed bread and baked bread, the traditional staple foods in China and many Western countries, were made by steaming and baking, respectively, using one piece of fermented wheat dough and then consumed by 16 healthy young volunteers. By detecting 38 cytokines, 12 metabolic enzymes, glucose, lactate, and nicotinamide adenine dinucleotide (NADH) in the serum, the cytokine network and central metabolic pathway network were investigated to compare the effects of the two staple foods on immunity and metabolism. Compared with steamed bread, baked bread increased (p < 0.05) concentrations of fractalkine and macrophage-derived chemokine, decreased (p < 0.05) the concentration of interleukin-1RA, increased (p < 0.05) the expression level of phosphofructokinase, and decreased (p < 0.05) the expression level of glucose-6-phosphate dehydrogenase in the serum. Two network analyses indicated that baked bread, as compared to the steamed bread, enhanced communication between immune cells, increased catabolism, and decreased anabolism. Further, a correlation analysis of cytokines and metabolic enzymes suggested that the two staple foods may affect metabolism by regulating the secretion of cytokines. These findings highlight how the same raw food material processed by different methods may have different impacts on immunity and metabolism in humans.

Low-protein diets supplemented with casein hydrolysate favor the microbiota and enhance the mucosal humoral immunity in the colon of pigs.

BACKGROUND: High-protein diets can increase the colonic health risks. A moderate reduction of dietary crude-protein (CP) level can improve the colonic bacterial community and mucosal immunity of pigs. However, greatly reducing the dietary CP level, even supplemented with all amino acids (AAs), detrimentally affects the colonic health, which may be due to the lack of protein-derived peptides. Therefore, this study evaluated the effects of supplementation of casein hydrolysate (peptide source) in low-protein (LP) diets, in comparison with AAs supplementation, on the colonic microbiota, microbial metabolites and mucosal immunity in pigs, aiming to determine whether a supplementation of casein hydrolysate can improve colonic health under very LP level. Twenty-one pigs (initial BW 19.90 ± 1.00 kg, 63 ± 1 days of age) were assigned to three groups and fed with control diet (16% CP), LP diets (13% CP) supplemented with free AAs (LPA) or casein hydrolysate (LPC) for 4 weeks. RESULTS: Compared with control diet, LPA and LPC diet decreased the relative abundance of Streptococcus and Escherichia coli, and LPC diet further decreased the relative abundance of Proteobacteria. LPC diet also increased the relative abundance of Lactobacillus reuteri. Both LP diets decreased concentrations of ammonia and cadaverine, and LPC diet also reduced concentrations of putrescine, phenol and indole. Moreover, LPC diet increased total short-chain fatty acid concentration. In comparison with control diet, both LP diets decreased protein expressions of Toll-like receptor-4, nuclear factor-κB, interleukin-1ß and tumor necrosis factor-α, and LPC diet further decreased protein expressions of nucleotide-binding oligomerization domain protein-1 and interferon-γ. LPC diet also increased protein expressions of G-protein coupled receptor-43, interleukin-4, transforming growth factor-ß, immunoglobulin A and mucin-4, which are indicators for mucosal defense activity. CONCLUSIONS: The results showed that supplementing casein hydrolysate showed beneficial effects on the colonic microbiota and mucosal immunity and barrier function in comparison with supplementing free AAs in LP diets. These findings may provide new framework for future nutritional interventions for colon health in pigs.

A framework for annotating human genome in disease context.

Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.