Roles and regulation of Aquaporin-3 in maintaining the gut health: an updated review

Aquaporin-3 (AQP3) is a predominant water channel protein expressed in the intestine, and plays important roles in the gut physiology and pathophysiology due to its permeability to water, glycerol and hydrogen peroxide. In this review, we systematically summarized the current understanding of the expression of AQP3 in the intestine of different species, and focused on the potential roles of AQP3 in water transport, different types of diarrhea and constipation, intestinal inflammation, intestinal barrier function, oxidative stress, and autophagy. These updated findings have supported that AQP3 may function as an important target in maintaining gut health of human and animals

Studying the Differences of Bacterial Metabolome and Microbiome in the Colon between Landrace and Meihua Piglets

This study was conducted to compare the microbiome and metabolome differences in the colon lumen from two pig breeds with different genetic backgrounds. Fourteen weaned piglets at 30 days of age, including seven Landrace piglets (a lean-type pig breed with a fast growth rate) and seven Meihua piglets (a fatty-type Chinese local pig breed with a slow growth rate), were fed the same diets for 35 days. Untargeted metabolomics analyses showed that a total of 401 metabolites differed between Landrace and Meihua. Seventy of these 401 metabolites were conclusively identified. Landrace accumulated more short-chain fatty acids (SCFAs) and secondary bile acids in the colon lumen. Moreover, expression of the SCFAs transporter (solute carrier family 5 member 8, SLC5A8) and receptor (G protein-coupled receptor 41, GPR41) in the colon mucosa was higher, while the bile acids receptor (farnesoid X receptor, FXR) had lower expression in Landrace compared to Meihua. The relative abundances of 8 genera and 16 species of bacteria differed significantly between Landrace and Meihua, and were closely related to the colonic concentrations of bile acids or SCFAs based on Pearson's correlation analysis. Collectively, our results demonstrate for the first time that there were differences in the colonic microbiome and metabolome between Meihua and Landrace piglets, with the most profound disparity in production of SCFAs and secondary bile acids

Effects of zinc oxide and condensed tannins on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment

This experiment was conducted to evaluate effects of zine oxide (ZnO) and condensed tannins (CT), independently or in combination, on the growth performance and intestinal health of weaned piglets in enterotoxigenic Escherichia coli (ETEC-K88)-challenged environment. Randomly divided 72 weaned piglets into 4 groups. Dietary treatments included the following: basic diet group (CON), 1,500 mg/kg zinc oxide group (ZnO), 1,000 mg/kg condensed tannins group (CT), and 1,500 mg/kg zinc oxide +1,000 mg/kg condensed tannins group (ZnO + CT). Dietary ZnO supplementation decreased diarrhea rate from 0 to 14 days, 15 to 28 days, and 0 to 28 days (p < 0.05) and no significant on growth performance. The effect of CT on reducing diarrhea rate and diarrhea index was similar to the results of ZnO. Compared with the CON group, ZnO increased the ileum villus height and improved intestinal barrier function by increasing the content of mucin 2 (MUC-2) in jejunum and ileum mucosa and the mRNA expression of zonula occludens-1 (ZO-1) in jejunum (p < 0.05) and the expression of Occludin in duodenum and ileum (p < 0.05). The effects of CT on intestinal barrier function genes were similar to that of ZnO. Moreover, the mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in jejunum and ileum was reduced in ZnO group (p < 0.05). And CT was also capable of alleviating diarrhea by decreasing CFTR expression and promote water reabsorption by increasing AQP3 expression (p < 0.05). In addition, pigs receiving ZnO diet had higher abundance of phylum Bacteroidetes, and genera Prevotella, and lower phylum Firmicutes and genera Lactobacillus in colonic contents. These results indicated that ZnO and CT can alleviate diarrhea and improve intestinal barrier function of weaned pigs in ETEC-challenged environment. In addition, the application of ZnO combined with CT did not show synergistic effects on piglet intestinal health and overall performance. This study provides a theoretical basis for the application of ZnO in weaning piglet production practices, we also explored effects of CT on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment

Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines

Dietary High Zinc Oxide Modulates the Microbiome of Ileum and Colon in Weaned Piglets

Dietary zinc oxide (ZnO) at pharmacological level has been widely used to prevent and treat diarrhea in weaning piglets. Despite its importance for promoting animal health and performance, the influence of microbiome profiles in intestinal tracts by ZnO needs to be comprehensively investigated. In this study, we conducted a comparative microbial community analysis in the ileum and colon of piglets fed by either control diet, high ZnO (3,000 mg/kg) supplement or antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) supplement. Our results showed that both high dietary ZnO and in-feed antibiotics supplementations significantly increased 5 phyla of Spirochaetes, Tenericutes, Euryarchaeota, Verrucomicrobia, TM7, and reduced 1 phyla of Chlamydiae in ileal digesta. The relative abundance of opportunistic pathogens Campylobacterales were decreased while Enterobacteriales were increased in ZnO or antibiotics-supplemented group when compared to the control. In the colon, the phyla Euryarchaeota, the genus Methanobrevibacter, and the species Methanobrevibacter smithii were drastically increased by high dietary ZnO supplementation when compared with other groups. The microbial functional prediction analysis showed that high dietary ZnO and in-feed antibiotics had a higher abundance of transporter pathway enrichment in the ileum when compared with the control. While in the colon high dietary ZnO had a higher abundant enrichment of methane metabolism involving energy supply when compared with other groups. Both high dietary ZnO and antibiotics increased the microbiota diversity of ileal digesta while they decreased the microbiota diversity of the colonic digesta. Collectively, these results suggested that dietary ZnO and in-feed antibiotics supplementations presented similar effect on ileal microbiota, and mainly affected the non-predominant microbiota

Effects of metabolic energy intervention on lipid content and liver transcriptome in finisher yellow-feathered chickens

High-energy diets improve growth rates and shorten the growth period while resulting in excessive fat deposition in the liver of birds. The effect of different energy diets on lipid content and liver transcriptome in finisher Huxu chickens was examined here. A total of 200 90-d-old Huxu chickens with an average BW of 1.08 kg were randomly divided into two dietary treatments. The birds were fed diets either containing 12.06 MJ ME/kg (low metabolic energy, LME) or 13.31 MJ ME/kg (high metabolic energy, HME) for 45 days. Chickens fed the HME diet had significantly higher total triglyceride and total cholesterol concentrations in both plasma and liver than did those fed the LME diet. Transcriptomic profiling showed 480 known differentially expressed genes (DEG), with 180 down-regulated and 300 up-regulated chickens from the HME diet compared with the LME diet. Notably, these genes were mostly enriched in lipid metabolism including the PPAR signalling pathway, fatty acid elongation, and glycerophospholipid metabolism. The relative mRNA expression level of 14 lipid metabolism-related genes, included 13 up-regulated (MBOAT2, PLA2G2E, AGPAT2, AGPAT3, PCYT2, PEMT, ELOVL2, HADHA, ACOT1L, FABP3, FABP1, PLIN1, RXRG) and one down-regulated (LCAT) gene. In conclusion, the present findings indicate that a high-energy diet likely regulates gene expression of the 14 lipid metabolism-related genes through the PPAR signalling pathway, fatty acid elongation, and glycerophospholipid metabolism resulting in excessive fat accumulation in the liver of Huxu chickens. These results provide a better understanding of the biological mechanisms by which the increased dietary energy induces fat accumulation in the liver.Highlights A high-energy diet without change in protein level induced excessive fat accumulation in the Huxu chickens. Chickens fed the high-energy diet had induced higher total triglyceride and total cholesterol concentrations in both plasma and liver. This study showed a comprehensive profile of hepatic gene expression in chickens with fatty liver induced by high energy

L-Arginine Inhibited Inflammatory Response and Oxidative Stress Induced by Lipopolysaccharide via Arginase-1 Signaling in IPEC-J2 Cells

This study aimed to explore the effect of L-arginine on lipopolysaccharide (LPS)-induced inflammatory response and oxidative stress in IPEC-2 cells. We found that the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), cluster of differentiation 14 (CD14), nuclear factor-kappaBp65 (NF-κBp65), chemokine-8 (IL-8), tumor necrosis factor (TNF-α) and chemokine-6 (IL-6) mRNA were significantly increased by LPS. Exposure to LPS induced oxidative stress as reactive oxygen species (ROS) and malonaldehyde (MDA) production were increased while glutathione peroxidase (GSH-Px) were decreased in LPS-treated cells compared to those in the control. LPS administration also effectively induced cell growth inhibition through induction of G0/G1 cell cycle arrest. However, compared with the LPS group, cells co-treatment with L-arginine effectively increased cell viability and promoted the cell cycle into the S phase; L-arginine exhibited an anti-inflammatory effect in alleviating inflammation induced by LPS by reducing the abundance of TLR4, MyD88, CD14, NF-κBp65, and IL-8 transcripts. Cells treated with LPS+L-arginine significantly enhanced the content of GSH-Px, while they decreased the production of ROS and MDA compared with the LPS group. Furthermore, L-arginine increased the activity of arginase-1 (Arg-1), while Arg-1 inhibitor abolished the protection of arginine against LPS-induced inflammation and oxidative stress. Taken together, these results suggested that L-arginine exerted its anti-inflammatory and antioxidant effects to protect IPEC-J2 cells from inflammatory response and oxidative stress challenged by LPS at least partly via the Arg-1 signaling pathway

Lactobacillus plantarum Enhanced IL-22 Production in Natural Killer (NK) Cells That Protect the Integrity of Intestinal Epithelial Cell Barrier Damaged by Enterotoxigenic Escherichia coli

Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier. The results showed that LP can efficiently increase protein levels of the natural cytotoxicity receptor (NCR) family, and the expression levels of IL-22 mRNA and protein in NK cells. Transfer of NK cells stimulated by LP conferred protection against ETEC K88-induced intestinal epithelial barrier damage in NCM460 cells. We found that NK cells stimulated by LP could partially offset the reduction in NCM460 cell monolayers transepithelial electrical resistance (TEER) caused by ETEC K88, and increase ZO-1 and occludin mRNA and protein expressions by ETEC K88-infected NCM460 cells. Furthermore, adding NK cells that were stimulated by LP to ETEC K88-infected NCM460cells, IL-22R1, p-Stat3, and p-Tyk2 expression by NCM460 cells was increased. Mechanistic experiment showed that NK cells stimulated by LP lost the function of maintaining TEER of NCM460 cells challenged with ETEC K88, when polyclonal anti-IL-22 antibody was used to block IL-22 production. Collectively, our results suggested that LP stimulation of NK could enhance IL-22 production, which might be able to provide defense against ETEC-induced damage to the integrity of intestinal epithelial barrier