The interaction between host and pathogen decidedly shapes the outcome of an infection, thus understanding this interaction is critical to the treatment of a pathogen-induced infection. Although research in this area of cell biology has yielded surprising findings regarding interactions between host and pathogen, understanding of the metabolic cross talk between host and pathogen is limited. At the site of infection, host and pathogen share similar or identical nutritional substrates and generate common metabolic products, thus metabolic cross talk between host and pathogen could profoundly affect the pathogenesis of an infection. In this review, we present results of a recent discovery of a metabolic interaction between host and pathogen from an amino acid (AA) metabolism-centric point of view. The host depends on AA metabolism to support defensive responses against pathogens, while the pathogens modulate AA metabolism for its own advantage. Some AA, such as arginine, asparagine, and tryptophan, are central points of competition between the host and pathogen. Thus, a better understanding of AA-mediated metabolic cross talk between host and pathogen will provide insight into fruitful therapeutic approaches to manipulate and prevent progression of an infection.

Short chain fatty acids (SCFAs, e.g., acetate, propionate, and butyrate) are a subset of fatty acids that are produced by gut microbiota during the fermentation of dietary fiber. They modulate different processes in the gastrointestinal tract and play various positive roles in mediating the intestinal health. Most beneficial roles of SCFAs in the gastrointestinal tract are mediated by directly activating its receptor, G protein-coupled receptor 43 (GPR43, also known as FFAR2). Various recent studies have demonstrated the role of GPR43 in intestinal inflammatory diseases, such as inflammatory bowel diseases. These SCFAs-mediated regulations of intestinal health are associated with neutrophil chemotaxis, T cell differentiation, activation, and subsequent cytokines production. Therefore, GPR43 could potentially be a drug target for intestinal inflammatory diseases. In this review, we review the current knowledge on the regulatory mechanisms associated with GPR43 in intestinal inflammation. The role of GPR43-mediated regulation of antibody responses is also discussed.

It has been suggested that gut microbiota play a critical role in maternal metabolic oxidative stress responses and offspring growth. However, whether the gut microbiota and oxidative stress status of the sows affect the litter performance during lactation is unclear. A total of 66 Yorkshire sows were identified as high (H) or low (L) litter performance sows based on litter weight at day 21 of lactation. Ten sows per group with similar parity, backfat thickness, and litter weight after cross-foster from the H or L group were collected randomly to analyze the oxidative stress and gut microbiota during lactation. The result showed that the serum total antioxidant capacity was higher in the H group, while 8-hydroxy-deoxyguanosine and thiobarbituric acid reactive substances were lower in the H group at farrowing. Four distinct clusters of bacteria were related to litter performance and reproductive periods of sows. Twelve differentially abundant taxa during gestation and 13 taxa during lactation were identified as potential biomarkers between the H group and the L group. Moreover, the litter performance and the antioxidant capacity of sows were positively correlated with Bacteroides_f__Bacteroidaceae but negatively with Phascolarctobacterium and Streptococcus. In conclusion, this study found that gut microbiota and oxidative stress were significantly correlated with the litter performance of sows during lactation.

Aims The aims were to examine whether oral sodium propionate supplementation regulate lipid metabolism through modulating gut microbiota. Methods and Results ICR male mice (26·98 ± 0·30 g) were randomly assigned to three groups (n = 10) and fed control diet (Con), high‐fat diet (HFD) and HFD plus propionate (Pro) respectively. In this study, we found that HFD increased the weight of final body, inguinal white adipose tissues (iWAT), epididymal white adipose tissue (eWAT) and perirenal white adipose tissue (pWAT), as well as the adipocyte mean area of iWAT and eWAT in mice (P < 0·05), whereas sodium propionate treatment reduced the weight of iWAT and pWAT as well as adipocyte mean area of iWAT in mice fed a HFD (P < 0·05). Moreover, in the iWAT, the mRNA expression of lipogenesis genes, including peroxisome proliferator activated receptor γ, acetyl‐CoA carboxylase and carnitine palmitoyl transferase‐1β, was upregulated by HFD challenge (P < 0·05), and the elevation of these genes was nearly reversed to the level of control diet‐fed mice by sodium propionate treatment. Meanwhile, sodium propionate treatment increased the hormone‐sensitive lipase mRNA expression in the iWAT of HFD‐fed mice (P < 0·05). High‐throughput pyrosequencing of the 16S rRNA demonstrated that sodium propionate treatment significantly recovered the gut microbiota dysbiosis in HFD‐fed mice, including the richness and diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. Furthermore, the HFD‐induced reductions in colonic levels of butyrate and valerate were reversed by sodium propionate treatment, which also normalized the serum LPS level seen in HFD‐fed mice to the levels of the control diet‐fed mice. Conclusions Collectively, these results indicated that sodium propionate treatment could improve lipid metabolism in HFD‐fed mice, and the potential mechanisms might be via regulating gut microbiota. Significance and Impact of the Study We demonstrated for the first time that oral sodium propionate significantly improved HFD‐induced dysbiosis of gut microbiota, indicating that the mitigative effect of propionate for HFD‐induced lipid dysmetabolism might be mediated by gut microbiota in mice.

Inflammatory bowel disease (IBD) in humans and animals is associated with bacterial infection and intestinal barrier dysfunction. Cecropin A, an antimicrobial peptide, has antibacterial activity against pathogenic bacteria. However, the effect of cecropin A on intestinal barrier function and its related mechanisms is still unclear. Here, we used porcine jejunum epithelial cells (IPEC-J2) as a model to investigate the effect and mechanism of cecropin A on intestinal barrier function. We found that cecropin A reduced Escherichia coli (E. coli) adherence to IPEC-J2 cells and downregulated mRNA expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Furthermore, cecropin A elevated the transepithelial electrical resistance (TER) value while reducing the paracellular permeability of the IPEC-J2 cell monolayer barrier. Finally, by using Western blotting, immunofluorescence and pathway-specific antagonists, we demonstrated that cecropin A increased ZO-1, claudin-1 and occludin protein expression and regulated membrane distribution and F-actin polymerization by increasing CDX2 expression. We conclude that cecropin A enhances porcine intestinal epithelial cell barrier function by downregulating the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. We suggest that cecropin A has the potential to replace antibiotics in the treatment of IBD due to its antibacterial activity on gram-negative bacteria and its enhancement effect on intestinal barrier function.

Background: Oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows. Methods: The placental oxidative stress status and vascular density of piglets with different birth weights: < 1.0 kg (low birth weight, LBW) and 1.4–1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n = 21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS from d 85 of gestation to d 21 of lactation, respectively. Placenta, serum, and colostrum samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs). Results: Compared with the NBW placentae, the LBW placentae showed increased oxidative damage and were vulnerable to angiogenesis impairment. Particularly, H₂O₂-induced oxidative stress prompted intracellular reactive oxygen species generation and inhibited the tube formation and migration of PVECs as well as the expression of vascular endothelial growth factor-A (VEGF-A) in vitro. However, dietary CS supplementation can alleviate oxidative stress and improve the reproductive performance of sows. Specifically, compared with the control group, dietary 100 mg/kg CS could (1) decrease the stillbirth and invalid rates, and increase both the piglet birth weight in the low yield sows and the placental efficiency; (2) increase glutathione and reduce malondialdehyde in both the serum and the colostrum of sows; (3) increase the levels of total antioxidant capacity and glutathione in LBW placentae; (4) increase the vascular density, the mRNA level of VEGF-A, and the immune-staining intensity of platelet endothelial cell adhesion molecule-1 in the LBW placentae. Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H₂O₂ inhibition of the proliferation, tube formation, and migration of PVECs. Meanwhile, inhibition of Stat3 significantly decreased the cell viability, tube formation and the VEGF-A protein level in CS pretreated with H₂O₂-cultured PVECs. Conclusions: The results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of LBW piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby increasing birth weight in low yield sows and reducing stillbirth rate. The in vitro data showed that the underlying mechanism for the positive effects of CS might be related to the activation of Stat3 in PVECs.