Links between fecal microbiota and the response to vaccination against influenza A virus in pigs.
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ABSTRACT:
SUBMITTER: Borey M
PROVIDER: S-EPMC8298503 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.
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Project description:The breed of pig can affect the diversity and composition of fecal microbiota, but there is a lack of research on the fecal microbiota of hybrid pigs. In this study, feces samples from Chuanxiang black pigs (a hybrid of Tibetan and Duroc pigs) aged 3 days (n = 24), 70 days (n = 31), 10 months (n = 13) and 2 years (n = 30) and Tibetan pigs aged 10 months (n = 14) and 2 years (n = 15) were collected and sequenced by 16S rRNA gene sequencing technology. We also measured the weight of all the tested pigs and found that the 10-month-old and two-year-old Chuanxiang black pigs weighed about three times the weight of Tibetan pigs of the same age. After comparing the genus-level microbiota composition of Tibetan pigs and Chuanxiang black pigs at 10 months and two years of age, we found that Treponema and Streptococcus were the two most abundant bacteria in Chuanxiang black pigs, while Treponema and Chirstensenellaceae_R.7_group were the two most abundant bacteria in Tibetan pigs. Prediction of microbial community function in adult Chuanxiang black pigs and Tibetan pigs showed changes in nutrient absorption, disease resistance, and coarse feeding tolerance. In addition, we also studied the changes in fecal microbiota in Chuanxiang black pigs at 3 days, 70 days, 10 months, and 2 years of age. We found that the ecologically dominant bacteria in fecal microbiota of Chuanxiang black pigs changed across developmental stages. For example, the highest relative abundance of 70-day-old Chuanxiang black pigs at the genus level was Prevotella. We identified specific microbiota with high abundance at different ages for Chuanxiang black pigs, and revealed that the potential functions of these specific microbiota were related to the dominant phenotype such as fast growth rate and strong disease resistance. Our findings help to expand the understanding of the fecal microbiota of hybrid pigs and provide a reference for future breeding and management of hybrid pigs.
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Project description:The backfat thickness of pigs not only affects the physical properties and taste of meat, but it also closely relates to the reproduction performance of sows. Accumulating evidence indicates that, apart from genetic factors, gut microbiota can also modulate the fat deposition and muscle growth. However, the differential microbiota in pigs with different backfat thickness, and whether microbiota affects backfat thickness, remains elusive. Firstly, 16S ribosomal RNA (16S rRNA) gene sequencing was performed on 62 fecal samples from pigs with different backfat thicknesses, and the compositions of microbiota among different groups with different backfat thicknesses were different. The abundance of Lactobacillus. reuteri (L. reuteri) and Prevotella sp RS2 was significantly higher in pigs with low-backfat thickness than that in pigs with middle and high-backfat thickness; meanwhile, the abundance of Desulfovibrio piger was significantly lower (p < 0.05) in pigs with low-backfat thickness. Furthermore, the functional profiling of microbial communities suggested that the abundance of isoquinoline alkaloid biosynthesis and styrene degradation were significantly lower (p < 0.05) in the low-backfat thickness group than that in middle and high-backfat thickness groups. Finally, L. reuteri fed to Meishan piglets was capable of improving the production performance and had the potential to reduce backfat thickness. This study provides new evidence that microbiota can regulate the phenotype of the host, and dietary supplementation with L. reuteri can improve the production performance of piglets.
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Project description:Influenza A viruses (IAVs) can infect a wide variety of bird and mammal species. Their genome is characterized by 8 RNA single stranded segments. The low proofreading activity of their polymerases and the genomic reassortment between different IAVs subtypes allow them to continuously evolve, constituting a constant threat to human and animal health. In 2009, a pandemic of an IAV highlighted the importance of the swine host in IAVs adaptation between humans and birds. The swine population and the incidence of swine IAV is constantly growing. In previous studies, despite vaccination, swine IAV growth and evolution were proven in vaccinated and challenged animals. However, how vaccination can drive the evolutionary dynamics of swine IAV after coinfection with two subtypes is poorly studied. In the present study, vaccinated and nonvaccinated pigs were challenged by direct contact with H1N1 and H3N2 independent swine IAVs seeder pigs. Nasal swab samples were daily recovered and broncho-alveolar lavage fluid (BALF) was also collected at necropsy day from each pig for swine IAV detection and whole genome sequencing. In total, 39 swine IAV whole genome sequences were obtained by next generation sequencing from samples collected from both experimental groups. Subsequently, genomic, and evolutionary analyses were carried out to detect both, genomic reassortments and single nucleotide variants (SNV). Regarding the segments found per sample, the simultaneous presence of segments from both subtypes was much lower in vaccinated animals, indicating that the vaccine reduced the likelihood of genomic reassortment events. In relation to swine IAV intra-host diversity, a total of 239 and 74 SNV were detected within H1N1 and H3N2 subtypes, respectively. Different proportions of synonymous and nonsynonymous substitutions were found, indicating that vaccine may be influencing the main mechanism that shape swine IAV evolution, detecting natural, neutral, and purifying selection in the different analyzed scenarios. SNV were detected along the whole swine IAV genome with important nonsynonymous substitutions on polymerases, surface glycoproteins and nonstructural proteins, which may have an impact on virus replication, immune system escaping and virulence of virus, respectively. The present study further emphasized the vast evolutionary capacity of swine IAV, under natural infection and vaccination pressure scenarios.
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Project description:Necrotizing enterocolitis (NEC) is an acute and life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventative therapy, but potential bacterial infection raise concern. Removal of bacteria from donor feces may reduce this risk while maintaining the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of bacteria-free fecal filtrate transfer (FFT). Using fecal material from healthy suckling piglets, we administered FMT rectally, or cognate FFT either rectally or oro-gastrically to formula-fed preterm, cesarean-delivered piglets as a model for preterm infants, We compared gut pathology and related safety parameters with saline controls, and analyzed ileal mucosal transcriptome to gauge the host e response to FMT and FFT treatments relative to control. Results showed that oro-gastric FFT prevented NEC, whereas FMT did not perform better than control. Moreover, FFT but not FMT reduced intestinal permeability, whereas FMT animals had reduced body weight increase and intestinal growth. Global gene expression of host mucosa responded to FMT but not FFT with increased and decreased bacterial and viral defense mechanisms, respectively. In conclusion, as preterm infants are extremely vulnerable to enteric bacterial infections, rational NEC-preventive strategies need incontestable safety profiles. Here we show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects. If translatable to preterm infants, this could lead to a change of practice and in turn a reduction in NEC burden.
2021-10-01 | GSE158878 | GEO
Project description:To determine the effect of astragalus and ginseng polysaccharides (APS, GPS) on immune response and improvement of H5N1 vaccine, 360-day-old broilers were randomly divided into 8 groups of 45 chicks, comprising APS groups (1-3); GPS groups (4-6); vaccine group (7); and blank control (8) (without polysaccharide and vaccine). From day 12 after hatch groups 1-3 were given APS and groups 4-6 with GPS both at 100, 200, and 400 (mg/kg), respectively. At day 15 after hatch, groups 1-7 were vaccinated with 0.3 mL H5N1 vaccine subcutaneously; daily weight gain (DWG) and serum Ig antibody (by HI-test) were measured on 3, 7, 14, and 28 days after vaccination. Serum antibody titers and expression of cytokines (IL-2, IL-10, I FN-γ, and TNF) were determined by ELISA and RT-PCR. Results revealed that all the polysaccharide groups were numerically increased in antibody levels and the expression of cytokines was significant (P < 0.05) in the APS and GPS groups compared to corresponding vaccine group and blank control. DWG was higher (P < 0.05) in 400 mg/kg APS groups than control groups. Thus oral supplements of GPS and APS have shown their potential in the improvement of immune response and could be used as adjuvant in a formulation of H5N1 vaccine.
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Project description:Interventions: The influenza virus vaccine is given in the period October/November 2011.
Primary outcome(s): Adequate rise in antibody titre.
Study Design: Randomized controlled trial, Open (masking not used), Active, Parallel
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Project description:We systematically assessed the transcriptomic changes of circulating leukocytes from whole blood of mice that had undergone polymicrobial sepsis. We systematically assessed the transcriptomic changes of liver tissue of mice that had undergone polymicrobial sepsis. Data indicate strong dissimilarities in early gene expression during murine sepsis affecting several pathways such as Toll-like receptor signalling, MAPK signalling, cytokine-cytokine receptor interaction, chemokine-signalling, and apoptosis during murine sepsis.
2016-12-01 | GSE70714 | GEO
Project description:Split inactivated influenza vaccines remain one of the primary preventative strategies against severe influenza disease in the population. However, current vaccines are only effective against a limited number of matched strains. The need for broadly protective vaccines is acute due to the high mutational rate of influenza viruses and multiple strain variants in circulation at any one time. The neuraminidase (NA) glycoprotein expressed on the influenza virion surface has recently regained recognition as a valuable vaccine candidate. We sought to broaden the protection provided by NA within the N1 subtype by computationally engineering consensus NA sequences. Three NA antigens (NA5200, NA7900, NA9100) were designed based on sequence clusters encompassing three major groupings of NA sequence space; (i) H1N1 2009 pandemic and Swine H1N1, (ii) historical seasonal H1N1 and (iii) H1N1 viruses ranging from 1933 till current times. Recombinant NA proteins were produced as a vaccine and used in a mouse challenge model. The design of the protein dictated the protection provided against the challenge strains. NA5200 protected against H1N1 pdm09, a Swine isolate from 1998 and NIBRG-14 (H5N1). NA7900 protected against all seasonal H1N1 viruses tested, and NA9100 showed the broadest range of protection covering all N1 viruses tested. By passive transfer studies and serological assays, the protection provided by the cluster-based consensus (CBC) designs correlated to antibodies capable of mediating NA inhibition. Importantly, sera raised to the consensus NAs displayed a broader pattern of reactivity and protection than naturally occurring NAs, potentially supporting a predictive approach to antigen design.
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