Investigating dysbiosis as a cause and predictor of intestinal pathology

Intestinal dysbiosis involves a shift in microbial composition and abundance within the gut and compelling evidence has highlighted the pivotal role dysbiosis plays in the onset and pathogenesis of numerous diseases, including inflammatory bowel disease (IBD), allergies and even mental health disorders. The intestinal microbiota is largely defined by host diet; a recent mouse model of total parenteral nutrition (TPN) showed that a dysbiotic shift in microbial dominance occurs following enteral nutrient depravation. Furthermore, metabolomics studies have identified that IBD patients can be discriminated from healthy based on their urinary metabolite profiles, but whether such profiles are accountable to intestinal dysbiosis remains uncertain. The research presented herein employed two human models; a novel TPN model in loop ileostomy patients, and patients with IBD, to assess microbial shifts and associated physiological consequences as well as determine whether urinary metabolite profiles are reflective of the intestinal microbiota. Using 16S rDNA-qPCR and -DGGE methods we revealed extensive variations in the microbiota of functional and defunctioned ileum following enteral nutrient deprivation, with a significant relative decrease in the Firmicutes phylum and concomitant increases in γ-Proteobacteria. Immunohistochemical techniques exposed a distinct physiological environment associated with a dysbiotic microbiota. Such environment was defined by reduced epithelial cell proliferation and mucosal atrophy that is likely due to altered host-microbiota interactions at the epithelial surface. We also observed post-operative complications that were potentially dysbiosis-mediated in almost 50% of the study cohort. Urinary NMR and Illumina 16S next-generation sequencing multi-omics statistical analyses identified correlations between dietary-associated urinary metabolites, particularly epicatechin, and distinct enterotype-like microbiota profiles. Application of this principle to prediction of IBD, as an example of a dysbiosis-associated disease, proved to be difficult due to limited sample numbers confounding interpatient variability. This research furthers the utilisation of intestinal microbiota as a therapeutic target, possibly via novel prebiotic administration to the defunctioned ileum with the potential to restore microbiota function prior to reanastomosis and reduce post-operative complications. Furthermore, it also provides promise for inexpensive, non-invasive detection of dysbiosis as a risk-factor of associated diseases. Further research, employing greater numbers of participants, is required to fully evaluate the potential predictive value of dysbiosis

Brief Report: An evaluation of an Australian autism-specific, early intervention programme

There is a relative paucity of evidence examining the effectiveness of early intervention for young children with Autism Spectrum Disorder, in particular those delivered through educationally-based programmes. This study aimed to evaluate the real world effectiveness of a community-based autism-specific early learning and intervention programme in Australia. Children enrolled between February 2010 and May 2013 who had a diagnosis of an Autism Spectrum Disorder was eligible to participate in the study. Fifty-nine children with a mean age of 3.98 years participated. Cognitive ability, language, autistic symptoms, and motor skills were assessed at baseline and follow up (12 months or at programme exit) using standardised measures. Pre- and post-measures were compared using paired sample t-tests. Significant improvements were found in receptive and expressive language, autism symptoms, and overall adaptive behaviour. No significant change was found in motor skills. Children with Autism Spectrum Disorder attending the community-based programme had significant gains particularly in domains of cognition and language. Study limitations are discussed

Evaluation of a standardised Vi poly-l-lysine ELISA for serology of Vi capsular polysaccharide antibodies

Typhoid vaccines based on protein-conjugated capsular Vi polysaccharide (TCVs) prevent typhoid in infants and young children. Analysis of the serum anti-Vi IgG response following immunisation against typhoid confirms the immunogenicity of TCVs and forms an important part of the pathway to licensing. Comparative studies could expedite the licencing process, and the availability of a standardised ELISA method alongside the 1st International Standard (IS) 16/138 for anti-typhoid capsular Vi polysaccharide IgG (human) will facilitate this process. To this end, a non-commercial ELISA based on a coat of Vi and poly-l-lysine (Vi-PLL ELISA) was evaluated by 10 laboratories. Eight serum samples, including IS 16/138, were tested in the standardised Vi-PLL ELISA (n = 10), a commercial Vi ELISA (n = 3) and a biotinylated Vi ELISA (n = 1). Valid estimates of potencies relative to IS 16/138 were obtained for all samples in the Vi-PLL ELISA and the commercial ELISA, with good repeatability and reproducibility evident from the study results and concordant estimates obtained by the two ELISA methods. The study demonstrates that the Vi-PLL ELISA can be used in clinical trial studies to determine the immunogenicity of TCVs

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

What Types of Challenges are Teachers Facing with 21st Century Professional Development?

This study aimed to identify the challenges facing teachers in their professional development across the primary, post-primary and tertiary educational sectors. Through the literature six main areas of investigation were identified: motivation, 21st century competencies, peer coaching, knowledge-sharing, professional learning communities and measurement/ assessment. The data was collected through 12 semi-structured interviews with teachers across the three sectors. A thematic analysis of the data was conducted. A number of themes were extracted, for example: environment, systems, culture and time. The findings of the study are discussed through interpretation of teacher’s experiences. The results identified challenges around individualistic work cultures, lack of purposeful systems of measurement, trust and fear issues, all of which were underpinned by time constraints. It was observed that there were more organisational structures at tertiary level. There was more commonality between primary and post-primary sectors. Despite the differences all three sectors have common challenges, such as effective knowledge-sharing and timely measurement to inform effective 21st century professional development

A Bayesian Multi-Task Approach for Detecting Global Microbiome Associations

AbstractMotivationThe human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current statistical techniques for microbiome association studies are limited by relying on measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome.ResultsIn this work, we develop a novel Bayesian multi-task approach for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We apply our method to simulated data and show that it allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease (Beamish, 2017), and a study of associations between diet and the gut microbiome in mice (Turnbaugh et al., 2009). We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.AvailabilityOur method is implemented using the R interface to the Stan Hamiltonian Monte Carlo sampler. Software for running our methods is available at https://github.com/FrankD/MicrobiomeGlobalAssociations.Contactf.dondelinger@lancaster.ac.uk</jats:sec

Loop ileostomy-mediated fecal stream diversion is associated with microbial dysbiosis

Loop ileostomy is an effective procedure to protect downstream intestinal anastomoses. Ileostomy reversal surgery is often carried out within 12 months of formation but is associated with substantial morbidity due to severe post-operative complications. Distal ileum is deprived of enteral nutrition and rendered inactive, often becoming atrophied and fibrotic. This study aimed to investigate the microbial and morphological changes that occur in the defunctioned ileum following loop ileostomy-mediated faecal stream diversion. Functional and defunctioned ileal resection tissue was obtained at the time of loop-ileostomy closure. Intrapatient comparisons, including histological assessment of morphology and epithelial cell proliferation, were performed on paired samples utilising the functional limb as control. Mucosal-associated microflora was quantified via determination of 16S rRNA gene copy number using qPCR analysis. DGGE with Sanger sequencing and qPCR methods profiled microflora to genus and phylum level, respectively. Reduced villous height and proliferation confirmed atrophy of the defunctioned ileum. DGGE analysis revealed that the microflora within defunctioned ileum is less diverse and convergence between defunctioned microbiota profiles was observed. Candidate Genera, notably Clostridia and Streptococcus, reduced in relative terms in defunctioned ileum. We conclude that Ileostomy-associated nutrient deprivation results in dysbiosis and impaired intestinal renewal in the defunctioned ileum. Altered host-microbial interactions at the mucosal surface likely contribute to the deterioration in homeostasis and thus may underpin numerous postoperative complications. Strategies to sustain the microflora prior to reanastomosis should be investigated

Models of practice for teachers of students on the autism spectrum

In Australia, students on the autism spectrum are increasingly being educated in inclusive settings. However, many teachers in mainstream educational settings do not feel they have the specialised knowledge or skills required for inclusive teaching of students on the autism spectrum. Teacher knowledge and confidence can influence the educational success of students on the autism spectrum, inclusive school practices, and teacher competency. Accessible and relevant evidence-based professional development can be an effective way of improving teachersâ™ competency for developing student social emotional, behavioural, communication, sensory, and learning skills. This chapter discusses a large school-based research project that used a Design-Based Research approach to design, validate, and trial two Models of Practice (MoP) for mainstream early and middle educators in Queensland, New South Wales, and Victoria. An MoP is a universally designed, evidence-based set of whole-class strategies for teachers which supports teachers to choose the most appropriate practices for fostering the inclusion of students on the spectrum. It also guides teacher decision-making and practice for curriculum content such as individualised lessons, and managing learning environments so as to provide an autism-friendly classroom infrastructure, social emotional adjustments, and behavioural supports. This chapter provides discussion and examples on how these practices can be supported in the classroom. Comments from participating teachers are included in this chapter to provide insightful suggestions for using the MoP briefs.</p

Delay in loop ileostomy reversal surgery does not impact upon post-operative clinical outcomes. Complications are associated with an increased loss of microflora in the defunctioned intestine

Loop ileostomy is a common surgical procedure to allow downstream tissue healing, with the aim of re-joining the bowel approximately 12 months later. The reversal procedure is associated with a substantial morbidity up to 40%. Our previous research demonstrated that defunctioned ileum becomes atrophied, with extensive microbial dysbiosis. This study sought to investigate the potential influence of delaying ileostomy reversal surgery upon both clinical and pathological outcomes. Post-operative clinical data was recorded, including routine blood test results, duration of hospital stay, length of time with stoma and incidence of post-operative complications. We measured ileal fibrosis and atrophy and assessed whether these, or dysbiosis, were impacted by the length of time a stoma was in place, or were linked to clinical outcomes. Associations between clinical data were investigated using scatterplot matrix analysis and t-tests. We found no differences in time between ileostomy formation and reversal in patients experiencing complications vs. individuals with no complications. Furthermore, there were no correlations between days with stoma and pathological measures, such as atrophy or fibrosis, and no ongoing increases in collagen production at the time of reversal surgery. This data suggests that the length of time a stoma is in place does not impact on the likelihood of complications. The incidence of complications is associated with increased loss of microbiota in the defunctioned ileum, but importantly, the decrease in bacteria is not linked to time with stoma. Microbiota diversity in the functional and defunctioned limb correlated within an individual, and was not significantly different between those who experienced complications following surgery vs. those that didn't. Microbiota diversity was also not significantly impacted through delay (>365 days) in stoma reversal. We propose that methods to restore intestinal microbiota numbers, and not necessarily their composition, prior to reversal should be explored to improve the clinical outcomes of ileostomy reversal surgery