Evaluation of synbiotics as gut health improvement agents against Shiga toxin-producing Escherichia coli isolated from the pig

Colibacillosis is one of the major health problems in young piglets resulting in poor health and death caused by Escherichia coli producing F18 pili and Shiga toxin 2e. It is pivotal to reduce colibacillosis in weaned piglets to enhance production performance. In this study, we evaluated synbiotics as the gut health improvement agents in the mouse model challenged with Shiga toxin-producing E. coli (STEC) isolated from piglets. Prebiotic lactulose was formulated with each 5.0 × 106 CFU/mL of Pediococcus acidilactici GB-U15, Lactobacillus plantarum GB-U17, and Lactobacillus plantarum GB 1-3 to produce 3 combinations of synbiotics. A total of 40 three weeks old BALB/c mice were randomly assigned to 4 groups (n = 10): a control group and 3 synbiotics treated groups. Each treatment groups were daily administrated with 5.0 × 106 CFU/mL of one synbiotics for the first week, and every 3 days during the second week. All the mice were challenged with 8.0 × 108 CFU/mL of STEC 5 days after animals began to receive synbiotics. Mice treated with synbiotics based on Pediococcus acidilactici GB-U15 and Lactobacillus plantarum GB-U17 significantly improved daily weight gain compared to mice in other groups. While mice treated with GB-U15 showed better fecal index, no significant differences were observed among groups. Gross lesion and histopathological evaluations showed that mice treated with GB-U15 moderately improved recovery from STEC infection. In conclusion, our results suggest that the synbiotics formulated with lactulose and Pediococcus acidilactici GB-U15 have potential benefits to prevent and improve colibacillosis in weaned piglets

Piglet gut microbial shifts early in life: causes and effects

Abstract The gut microbiome has long been known to play fundamentally important roles in the animal health and the well-being of its host. As such, the establishment and maintenance of a beneficial gut microbiota early in life is crucial in pigs, since early gut colonizers are pivotal in the establishment of permanent microbial community structures affecting the health and growth performance of pigs later in life. Emphasizing this importance of early gut colonizers, it is critical to understand the factors impacting the establishment of the piglet gut microbiome at weaning. Factors include, among others, diet, in-feed antibiotics, probiotics and prebiotic administration. The impact of these factors on establishment of the gut microbiome of piglets at weaning includes effects on piglet gut microbial diversity, structure, and succession. In this review, we thoroughly reviewed the most recent findings on the piglet gut microbiome shifts as influenced by weaning, and how these microbiome changes brought about by various factors that have been shown to affect the development of microbiota in piglets. This review will provide a general overview of recent studies that can help to facilitate the design of new strategies to modulate the gut microbiome in order to enhance gastrointestinal health, growth performance and well-being of piglets

Oral Vaccination against Lawsoniaintracellularis Changes the Intestinal Microbiome in Weaned Piglets

Lawsoniaintracellularis, which causes porcine proliferative enteropathy (PPE), is a common swine intestinal pathogen that is prevalent in pig production sites worldwide. In this study, the alteration in the microbiome composition of weaned pigs was investigated in response to vaccination against L. intracellularis, using 16S rRNA gene sequencing. A total of 64 crossbred (Duroc × [Landrace × Yorkshire]) healthy weanling pigs weaned at 4 weeks of age were randomly assigned to four treatment groups (four pigs/pen; four pens/treatment), using a randomized complete block design for the 42-day trial. Pigs in the treatment groups were orally administered with three different doses (1 dose = 2 mL) of vaccine against L. intracellularis (Enterisol® Ileitis, Boehringer Ingelheim Vetmedica GmbH), namely the following: LAW1 (0.5 dose), LAW2 (1 dose), LAW3 (2 dose). A non-vaccinated group served as a negative control (CONT). Alpha diversity analysis revealed that vaccination led to significant changes in species evenness but not species richness of the gut microbiota. Beta diversity analysis revealed that vaccination against L. intracellularis caused a significant shift in the microbial community structure. At the genus level, there was a significant increase in Streptococcus and a significant decrease in Clostridium in the fecal microbiota of vaccinated pigs, regardless of dose

The dynamics of the piglet gut microbiome during the weaning transition in association with health and nutrition

Abstract Background Understanding the composition of the microbial community and its functional capacity during weaning is important for pig production as bacteria play important roles in the pig’s health and growth performance. However, limited information is available regarding the composition and function of the gut microbiome of piglets in early-life. Therefore, we performed 16S rRNA gene and whole metagenome shotgun sequencing of DNA from fecal samples from healthy piglets during weaning to measure microbiome shifts, and to identify the potential contribution of the early-life microbiota in shaping piglet health with a focus on microbial stress responses, carbohydrate and amino acid metabolism. Results The analysis of 16S rRNA genes and whole metagenome shotgun sequencing revealed significant compositional and functional differences between the fecal microbiome in nursing and weaned piglets. The fecal microbiome of the nursing piglets showed higher relative abundance of bacteria in the genus Bacteroides with abundant gene families related to the utilization of lactose and galactose. Prevotella and Lactobacillus were enriched in weaned piglets with an enrichment for the gene families associated with carbohydrate and amino acid metabolism. In addition, an analysis of the functional capacity of the fecal microbiome showed higher abundances of genes associated with heat shock and oxidative stress in the metagenome of weaned piglets compared to nursing piglets. Conclusions Overall, our data show that microbial shifts and changes in functional capacities of the piglet fecal microbiome resulted in potential reductions in the effects of stress, including dietary changes that occur during weaning. These results provide us with new insights into the piglet gut microbiome that contributes to the growth of the animal

Discovering dominant tumor immune archetypes in a pan-cancer census

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy

Discovering dominant tumor immune archetypes in a pan-cancer census

International audienc

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. Funding: British Heart Foundation and Stroke Association.restrictio