Explore the vast range of titles available.

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus with worldwide distribution. PDCoV belongs to the Deltacoronavirus (DCoV) genus, which mainly includes avian coronaviruses (CoVs). PDCoV has the potential to infect human and chicken cells in vitro, and also has limited infectivity in calves. However, the origin of PDCoV in pigs, the host range, and cross-species infection of PDCoV still remain unclear. To determine whether PDCoV really has the ability to infect chickens in vivo, the three lines of chicken embryos and specific pathogen free (SPF) chickens were inoculated with PDCoV HNZK-02 strain to investigate PDCoV infection in the current study. Our results indicated that PDCoV can infect chicken embryos and could be continuously passaged on them. Furthermore, we observed that PDCoV-inoculated chickens showed mild diarrhea symptoms and low fecal viral RNA shedding. PDCoV RNA could also be detected in multiple organs (lung, kidney, jejunum, cecum, and rectum) and intestinal contents of PDCoV-inoculated chickens until 17 day post-inoculation by real-time quantitative PCR (qRT-PCR). A histology analysis indicated that PDCoV caused mild lesions in the lung, kidney, and intestinal tissues. These results prove the susceptibility of chickens to PDCoV infection, which might provide more insight about the cross-species transmission of PDCoV.

The gut microbiota plays a central role in regulating host metabolism. While substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little is known about how key members of the maternal gut microbiota can influence feto-placental growth. Notably, in pregnant women, Bifidobacterium represents a key beneficial microbiota genus, with levels observed to increase across pregnancy. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental structure and nutrient transporter capacity, with implications for fetal metabolism and growth. Maternal and placental metabolome were affected by maternal gut microbiota ( i.e. acetate, formate and carnitine). Histological analysis of the placenta confirmed that Bifidobacterium modifies placental structure via changes in Igf2P0, Dlk1, Mapk1 and Mapk14 expression. Additionally, B. breve UCC2003 , acting through Slc2a1 and Fatp1-4 transporters, was shown to restore fetal glycaemia and fetal growth in association with changes in the fetal hepatic transcriptome. Our work emphasizes the importance of the maternal gut microbiota on feto-placental development and sets a foundation for future research towards the use of probiotics during pregnancy.

Transgenic mice expressing the mouse interleukin 33 (IL-33) gene driven by a keratin 14 promoter were generated. The skin-selective expression of the IL-33 gene was enhanced, and intense immunofluorescence for IL-33 was evident in the nuclei of the epidermis. Spontaneous itchy dermatitis developed in those mice at 6–8 wk of age in specific pathogen-free conditions. In the lesional skin, the epidermis was thickened and the eosinophils were infiltrated with increased expression of the eosinophil peroxidase and major basic protein genes. Mast cells were also abundant there, and blood histamine and total IgE levels were high. Those phenotypes closely resemble the features of atopic dermatitis. In peripheral blood and lesional skin, IL-5, IL-13, regulated upon activation, normally T-expressed, and presumably secreted (RANTES)/CCL5, and Eotaxin 1/CCL11 were increased, whereas TNF-α, IFN-γ, and thymic stromal lymphopoietin (TSLP) were unaltered. Furthermore, the proportion of group 2 innate lymphoid cells (ILC2s), which produce IL-5, were significantly increased in the lesional skin, peripheral blood, and regional lymph nodes. The dermatitis with eosinophil infiltration was improved by the administration of an anti-IL-5 antibody. These results suggest that the expression of IL-33 in the skin activates an immune response involving ILC2 and that this process might play a crucial role in the pathogenesis of allergic inflammation that is characteristic of atopic dermatitis.

In the representative gut bacterium Lactobacillus plantarum , we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty acids and revealed in detail the metabolic pathway that generates hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans -fatty acids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fatty acids are generated through polyunsaturated fatty acids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fatty acid composition.

Duck Hepatitis A Virus type 1 (DHAV-1) is a highly pathogenic virus that causes severe mortality in ducklings and results in substantial economic losses to the global duck industry. Live-attenuated DHAV vaccine remains one of the most effective strategies for controlling this disease. We developed a safe and effective live attenuated vaccine candidate E23-SP80 adapted to specific-pathogen-free (SPF) chicken embryos by serial passage of a field isolate. The E23-SP80 exhibited an adaptive growth capacity in SPF chicken embryos with a viral titer of 107.25 ELD50/0.2 mL and lost its pathogenicity in 2-day-old Cherry Valley ducklings. The vaccine strain maintained its attenuation and showed no virulence reversion after back propagation into 2-day-old ducklings for five rounds. An immunizing dose of only 103.0 ELD₅₀ of E23-SP80 could provide 100% protection against challenge with lethal parental DHAV-1 strain. After a single intramuscular vaccination, virus-neutralizing antibody titers exceeded 9 log2 from 7 to 28 days post-vaccination and the titers were markedly higher than those of a commercial vaccine. Genomic analysis of E23-SP9 and E23-SP80 revealed fifteen amino acid substitutions, most of which were located in VP1 and 2A2 proteins, and the hypervariable region of VP1 (T180I and D193N) might contribute to attenuation. These results suggest that E23-SP80 strain is a promising commercial vaccine candidate for the prevention and control of DHAV-1 infection. •The attenuated vaccine E23-SP80 for duck hepatitis A virus type 1 was developed.•A 103.0 ELD50 immunizing dose of E23-SP80 conferred 100% protection.•The NT levels of E23-SP80 exceeded 9 log2 within 4 weeks post-immunization.•VP1 amino acid substitutions T180I and D193N may contribute to viral attenuation.

•A chimeric fiber protein was designed merging epitopes from two different FAdV species.•The chimeric fiber was able to protect chickens against HHS and IBH.•Protection was associated with high antibody response but no neutralizing activity.•This is the first subunit vaccine protecting chickens from multiple FAdV diseases. In the past decades, fowl adenovirus (FAdV)-related diseases became an increasing concern for the poultry industry worldwide. Various immunization strategies against FAdVs have been experimentally investigated, with a particular focus on subunit vaccines against hepatitis-hydropericardium syndrome (HHS), caused by FAdV serotype 4, and inclusion body hepatitis (IBH), caused by serotypes 2, 8a, 8b and 11. In this study, we extended our innovative concept of recombinant chimeric fiber proteins to design a novel chimera combining epitopes from two distinct serotypes, FAdV-4 and -11, and we investigated its efficacy to simultaneously protect chickens against HHS and IBH. Specific pathogen-free chickens were vaccinated with the novel recombinant chimeric fiber and subsequently challenged with either a HHS- or IBH-causing strain. Vaccinated/challenged birds exhibited a reduction of clinical signs, limited hepatomegaly and lower levels of AST compared to the respective challenge controls. Furthermore, the vaccine prevented atrophy of HHS-affected lymphoid organs, such as thymus and bursa of Fabricius, and viral load in the target organs was significantly reduced. Clinical protection was associated with high levels of pre-challenge antibodies measured on ELISA plates coated with the vaccination antigen. Interestingly, the development of neutralizing antibodies was limited against FAdV-11 and absent against FAdV-4, indicating that protection granted by such an antigen may be linked to different immunization pathways. In conclusion, we proved that the concept of chimeric fiber vaccines can be extended across viral species boundaries and represents the first single-component FAdV subunit vaccine providing comprehensive protection against different FAdV-associated diseases.

Type 2 diabetes mellitus (T2DM) was reported to be associated with impaired immune response and alterations in microbial composition and function. However, the underlying mechanism remains elusive. To investigate the association among retinoic acid-inducible gene-I-like receptors (RLRs) signaling pathway, intestinal bacterial microbiome, microbial tryptophan metabolites, inflammation, and a longer course of T2DM, 14 patients with T2DM and 7 healthy controls were enrolled. 16S rRNA amplicon sequencing and untargeted metabolomics were utilized to analyze the stool samples. RNA sequencing (RNA-seq) was carried out on the peripheral blood samples. Additionally, C57BL/6J specific pathogen-free (SPF) mice were used. It was found that the longer course of T2DM could lead to a decrease in the abundance of probiotics in the intestinal microbiome. In addition, the production of microbial tryptophan derivative skatole declined as a consequence of the reduced abundance of related intestinal microbes. Furthermore, low abundances of probiotics, such as Bacteroides and Faecalibacterium , could trigger the inflammatory response by activating the RLRs signaling pathway. The increased level of the member of TNF receptor-associated factors (TRAF) family, nuclear factor kappa-B ( NF-κB ) activator ( TANK ), in the animal colon activated nuclear factor kappa B subunit 2 ( NFκB2 ), resulting in inflammatory damage. In summary, it was revealed that the low abundances of probiotics could activate the RLR signaling pathway, which could in turn activate its downstream signaling pathway, NF-κB, highlighting a relationship among gut microbes, inflammation, and a longer course of T2DM. Key points Hyperglycemia may suppress tryptophanase activity. The low abundance of Bacteroides combined with the decrease of Dopa decarboxylase (DDC) activity may lead to the decrease of the production of tryptophan microbial derivative skatole, and the low abundance of Bacteroides or reduced skatole may further lead to the increase of blood glucose by downregulating the expression of glucagon-like peptide-1 (GLP1). A low abundance of anti-inflammatory bacteria may induce an inflammatory response by triggering the RLR signaling pathway and then activating its downstream NF-κB signaling pathway in prolonged T2DM.

•Level of hygiene is associated with the severity of diabetic kidney disease (DKD).•The gut environment of mice differs according to the hygiene level of their housing.•Dysbiosis owing to living conditions may contribute to the severity of DKD. Although the effects of an unhealthy diet on the risks of diabetes and its renal complications are well understood, the effects of hygiene status have not been fully elucidated. We created four groups of mice according to the diet fed (standard [SD] or high-fat [HFD]) and their living environment (conventional [CV] or specific pathogen-free [SPF]), and characterized the extent of their kidney pathology, their gut microbiota, and their fecal short-chain fatty acid (SCFA) concentrations. The body masses and glycated hemoglobin levels of the HFD and CV groups were significantly higher than those of the SD and SPF groups, respectively. The renal mRNA expression of markers of inflammation and fibrosis and the protein level of CD31 were higher in the HFD and CV groups than in the SD and SPF groups, respectively. Although the alpha diversities and total SCFA concentrations of the HFD and CV groups were significantly lower than those of the SD and SPF groups, respectively, the mRNA expression of genes involved in inflammation, innate immunity, tight junctions, and glucose transporters in the gut was only affected by HFD. Gut microbial dysbiosis, owing to the combined effects of inappropriate diet and excessive hygiene, accompanied by lower intestinal SCFA production, may contribute to the development and/or progression of diabetes and diabetic kidney disease through the induction of inflammation and fibrosis.