High fat diet-induced hyperlipidemia and tissue steatosis in rabbits through modulating ileal microbiota.

High-fat diet (HFD) and overnutrition are important starting factors that may alter intestinal microbiota, lipid metabolism, and systemic inflammation. However, there were few studies on how intestinal microbiota contributes to tissue steatosis and hyperlipidemia. Here, we investigated the effect of lipid metabolism disorder-induced inflammation via toll-like receptor 2 (TLR-2), toll-like receptor 4 (TLR-4), and nuclear factor-κB (NF-κB) pathways at the intestinal level in response to HFD. Twenty 80-day-old male New Zealand White rabbits were randomly divided into the normal diet group (NDG) and the high-fat diet group (HDG) for 80 days. Growth performance, blood biochemical parameters, lipid metabolism, inflammation, degree of tissue steatosis, and intestinal microbial composition were measured. HFD increased the relative abundance of Christensenellaceae_R_7_group, Marvinbryantia, Akkermansia etc., with a reduced relative abundance of Enterorhabdus and Lactobacillus. Moreover, HFD caused steatosis in the liver and abdominal fat and abnormal expression of some genes related to lipid metabolism and tight junction proteins. The TLR-2, TLR-4, NF-κB, TNF-α, and IL-6 were confirmed by overexpression with downregulation of IL-10. Serum biochemical indices (TG, TCHO, LDL-C, and HDL-C) were also increased, indicating evidence for the development of the hyperlipidemia model. Correlation analysis showed that this microbial dysbiosis was correlated with lipid metabolism and inflammation, which were associated with the intestinal tract's barrier function and hyperlipidemia. These results provide an insight into the relationship between HFD, the intestinal microbiota, intestinal barrier, tissue inflammation, lipid metabolism, and hyperlipidemia. KEY POINTS: • High-fat diet leads to ileal microbiota disorders • Ileal microbiota mediates local and systemic lipid metabolism disorders and inflammation • There is a specific link between ileal microbiota, histopathology, and hyperlipidemia.

Adhesive mechanism of different Salmonella fimbrial adhesins.

Salmonellosis is a serious threat to human and animal health. Salmonella adhesion to the host cell is an initial and most crucial step in the pathogenesis of salmonellosis. Many factors are involved in the adhesion process of Salmonella infection. Fimbriae are one of the most important factors in the adhesion of Salmonella. The Salmonella fimbriae are assembled in three types of assembly pathways: chaperon-usher, nucleation-precipitation, and type IV fimbriae. These assembly pathways lead to multiple types of fimbriae. Salmonella fimbriae bind to host cell receptors to initiate adhesion. So far, many receptors have been identified, such as Toll-like receptors. However, several receptors that may be involved in the adhesive mechanism of Salmonella fimbriae are still un-identified. This review aimed to summarize the types of Salmonella fimbriae produced by different assembly pathways and their role in adhesion. It also enlisted previously discovered receptors involved in adhesion. This review might help readers to develop a comprehensive understanding of Salmonella fimbriae, their role in adhesion, and recently developed strategies to counter Salmonella infection.

Polysaccharide from Smilax glabra Roxb Mitigates Intestinal Mucosal Damage by Therapeutically Restoring the Interactions between Gut Microbiota and Innate Immune Functions.

Smilax glabra Roxb (S. glabra) is a conventional Chinese medicine that is mainly used for the reliability of inflammation. However, bioactive polysaccharides from S. glabra (SGPs) have not been thoroughly investigated. Here, we demonstrate for the first time that SGPs preserve the integrity of the gut epithelial layer and protect against intestinal mucosal injury induced by dextran sulfate sodium. Mechanistically, SGPs mitigated colonic mucosal injury by restoring the association between the gut flora and innate immune functions. In particular, SGPs increased the number of goblet cells, reduced the proportion of apoptotic cells, improved the differentiation of gut tight junction proteins, and enhanced mucin production in the gut epithelial layer. Moreover, SGPs endorsed the propagation of probiotic bacteria, including Lachnospiraceae bacterium, which strongly correlated with decreased pro-inflammatory cytokines via the blocking of the TLR-4 NF-κB and MyD88 pathways. Overall, our study establishes a novel use of SGPs for the treatment of inflammatory bowel disease (IBD)-associated mucosal injury and provides a basis for understanding the therapeutic effects of natural polysaccharides from the perspective of symbiotic associations between host innate immune mechanisms and the gut microbiome.

Chlorogenic acid is a positive regulator of MDA5, TLR7 and NF-κB signaling pathways mediated antiviral responses against Gammacoronavirus infection.

Chlorogenic acid (CGA) is a phenolic compound that has been well studied for its antiviral, anti-inflammatory and immune stimulating properties. This research was aimed to focus on the antiviral properties of CGA on infectious bronchitis virus (IBV) in vivo and in vitro for the very first time. The outcome of in vitro experiments validated that, out of five previously reported antiviral components, CGA significantly reduced the relative mRNA expression of IBV-N in CEK cells. At high concentration (400 mg/kg), CGA supplementation reduced IBV-N mRNA expression levels and ameliorated the injury in trachea and lungs. The mRNA expression levels of IL-6, IL-1ß, IL-12, and NF-κB were considerably turned down, but IL-22 and IL-10 were enhanced in trachea. However, CGA-H treatment had considerably increased the expression levels of MDA5, MAVS, TLR7, MyD88, IRF7, IFN-ß and IFN-α both in trachea and lungs. Moreover, CGA-H notably induced the CD3+, CD3+ CD4+ and CD4+/CD8+ proliferation and significantly increased the IgA, IgG, and IgM levels in the serum. In conclusion, these results showed that at high concentration CGA is a strong anti-IBV compound that can effectively regulate the innate immunity through MDA5, TLR7 and NF-κB signaling pathways and have the potential to induce the cell mediated and humoral immune response in IBV infected chickens.

Anti-chicken type I IFN countermeasures by major avian RNA viruses.

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-ß, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) recognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry.

Current Findings on Gut Microbiota Mediated Immune Modulation against Viral Diseases in Chicken.

Chicken gastrointestinal tract is an important site of immune cell development that not only regulates gut microbiota but also maintains extra-intestinal immunity. Recent studies have emphasized the important roles of gut microbiota in shaping immunity against viral diseases in chicken. Microbial diversity and its integrity are the key elements for deriving immunity against invading viral pathogens. Commensal bacteria provide protection against pathogens through direct competition and by the production of antibodies and activation of different cytokines to modulate innate and adaptive immune responses. There are few economically important viral diseases of chicken that perturb the intestinal microbiota diversity. Disruption of microbial homeostasis (dysbiosis) associates with a variety of pathological states, which facilitate the establishment of acute viral infections in chickens. In this review, we summarize the calibrated interactions among the microbiota mediated immune modulation through the production of different interferons (IFNs) ILs, and virus-specific IgA and IgG, and their impact on the severity of viral infections in chickens. Here, it also shows that acute viral infection diminishes commensal bacteria such as Lactobacillus, Bifidobacterium, Firmicutes, and Blautia spp. populations and enhances the colonization of pathobionts, including E. coli, Shigella, and Clostridial spp., in infected chickens.