Microbiota-gut-brain axis in health and neurological disease: Interactions between gut microbiota and the nervous system.

Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.

Disturbances of the gut microbiota-derived tryptophan metabolites as key actors in vagotomy-induced mastitis in mice.

Previous studies have demonstrated that gut microbiota dysbiosis promotes the development of mastitis. The interaction of the vagus nerve and gut microbiota endows host homeostasis and regulates disease development, but whether the vagus nerve participates in the pathogenesis of mastitis is unclear. Here, vagotomized mice exhibit disruption of the blood-milk barrier and mammary gland inflammation. Notably, mastitis and barrier damage caused by vagotomy are dependent on the gut microbiota, as evidenced by antibiotic treatment and fecal microbiota transplantation. Vagotomy significantly alters the gut microbial composition and tryptophan metabolism and reduces the 5-hydroxyindole acetic acid (5-HIAA) level. Supplementation with 5-HIAA alleviates vagotomy-induced mastitis, which is associated with the activation of the aryl hydrocarbon receptor (AhR) and subsequent inhibition of the NF-κB pathway. Collectively, our findings indicate the important role of the vagus-mediated gut-mammary axis in the pathogenesis of mastitis and imply a potential strategy for the treatment of mastitis by targeting the vagus-gut microbiota interaction.

Prostaglandin D2 is involved in the regulation of inflammatory response in Staphylococcus aureus-infected mice macrophages.

Staphylococcus aureus (S. aureus) is one of the most infamous and widespread bacterial pathogens, causing a hard-to-estimate number of uncomplicated skin infections and probably hundreds of thousands to millions of more severe, invasive infections globally per year. S. aureus may also be acquired from animals, especially in the livestock industry. The interaction mechanism of host and S. aureus has significance for finding ways to against S. aureus infection and control inflammatory response of host, while the molecular biological activities after S. aureus infection, particular in inflammatory and immune cells are not fully clear. The present study aimed to explore whether pattern recognition receptors (PRRs) mediate prostaglandin D2 (PGD2) synthesis and PGD2 participates in the regulation of inflammatory response in macrophages during S. aureus infection or synthetic bacterial lipopeptide (Pam2CSK4) stimulation. PGD2 secretion level was enhanced by mice peritoneal macrophages infected with the S. aureus. The results indicated that PGD2 secretion was impaired in S. aureus infected-macrophages from toll-like receptors 2 (TLR2)-deficient and NLR pyrin domain-containing 3 (NLRP3)-deficient mice. PGD2 synthetase (hematopoietic PGD synthase, HPGDS) inhibitors could reduce the activation of macrophage mitogen-activated protein kinase (MAPK)/nuclear factor-κ-gene binding (NF-κB) signaling pathways. HPGDS inhibition impaired cytokines (TNF-α, IL-1ß, IL-10 and RANTES) secretion and macrophage phagocytosis during S. aureus infection. In addition, inhibition of endogenous PGD2 synthesis was unable to affect the TLR2 and NLRP3 expression in S. aureus-infected macrophages. Taken together, macrophage PGD2 secretion after S. aureus infection depended on receptors TLR2 and NLRP3, and the induced PGD2 participated in the regulation of inflammatory response in S. aureus-infected macrophages. Interestingly, it was found that exogenous PGD2 down-regulated the cytokines secretion and had no effect on phagocytosis in the S. aureus-infected macrophages.

ZEA mediates autophagy through the ROS-AMPK-m-TOR pathway to enhance the susceptibility of mastitis induced by Staphylococcus aureus in mice.

Mastitis is an inflammatory response of the mammary tissue caused by pathogenic bacterial infections, especially Staphylococcus aureus (S. aureus). Zearalenone (ZEA) is one of the common mycotoxins in moldy feed, which usually affects the cow's resistance to pathogenic microorganisms. However, it is not well understood whether ZEA affects the development of mastitis. Therefore, this study aimed to investigate the role of ZEA in the development of S. aureus-induced mastitis in mice. The results showed that administered daily by gavage for one week of ZEA (40 mg/kg) aggravated the severity of mastitis induced by S. aureus. Furthermore, we found that ZEA promotes the adhesion and invasion of S. aureus into mouse mammary epithelial cells (MMEC) by activating autophagy, and the activation of autophagy mediated by ROS-AMPK-m-TOR pathway. Taken together, the results showed that ZEA enhances S. aureus-induced mastitis susceptibility through activating autophagy mediated by ROS-AMPK-mTOR signaling pathway.

Braun Lipoprotein Protects against Escherichia coli-Induced Inflammatory Responses and Lethality in Mice.

Escherichia coli (E. coli), a Gram-negative bacterium, is an important pathogen that causes several mammalian diseases. The outer membrane components of E. coli, namely, lipopolysaccharide (LPS) and bacterial lipoprotein, can induce the host innate immune response through pattern recognition receptors (PRRs). However, the detailed roles of the E. coli Braun lipoprotein (BLP) in the regulation of host inflammatory response to E. coli infection remain unclear. In this study, we sought to determine the effects of BLP on E. coli-induced host inflammatory response and lethality using mouse models. Experiments using the E. coli DH5α strain (BLP-positive), E. coli JE5505 strain (BLP-negative), and E. coli JE5505 strain combined with BLP indicated that the presence of BLP could alleviate mortality and organ (liver and lung) damage and decrease proinflammatory cytokine (tumor necrosis factor alpha [TNF-α] and interleukin-1ß [IL-1ß]) and chemokine (regulated on activation normal T-cell expressed and secreted [RANTES]) production in mouse serum and organs. Conversely, E. coli JE5505, E. coli DH5α strain, and E. coli JE5505 combined with BLP treatment induce enhanced anti-inflammatory cytokine (interleukin 10 [IL-10]) production in mouse serum and organs. In addition, BLP could regulate the secretion of proinflammatory cytokines (TNF-α and IL-1ß), chemokines (RANTES), and anti-inflammatory factors (IL-10) through mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways in macrophages. Altogether, our results demonstrate that the bacterial component BLP plays crucial and protective roles in E. coli-infected mice, which may influence the outcome of inflammation in host response to E. coli infection. IMPORTANCE In this study, we investigated the roles of bacterial outer membrane component BLP in regulating inflammatory responses and lethality in mice that were induced by a ubiquitous and serious pathogen, Escherichia coli. BLP could alleviate the mortality of mice and organ damage, as well as decrease proinflammatory cytokines and chemokine production and enhance anti-inflammatory cytokine production in mouse serum and organs. Overall, our results demonstrate that the bacterial component BLP plays crucial and protective roles in E. coli-infected mice through regulating the production of an inflammatory mediator, which may influence the outcome of inflammation in host response to E. coli infection. Our findings provide new information about the basic biology involved in immune responses to E. coli and host-bacterial interactions, which have the potential to translate into novel approaches for the diagnosis and treatment of E. coli-related medical conditions, such as bacteremia and sepsis.