Abstract Background Patients over the age of 50 years and those who are on immunosuppressive therapy are at increased risk of contracting Herpes Zoster (Shingles). Most recent international (ECCO) guidelines have recommended that all patients commencing on JAK inhibitors be vaccinated to ensure optimum protection against the Shingles Virus. Shingrix (non-live) vaccine is available in Ireland but is not reimbursed by the HSE, therefore patients are required to pay privately. Unfortunately, due to the significant cost of receiving this vaccine in the community the uptake among IBD patients is minimal. The aim of this clinic was: •To provide optimum protection against the Shingles virus to all IBD patients commencing on a JAK inhibitor •To eliminate the burden of shingles for immunocompromised patients with IBD •To ensure evidence-based practice is adhered to in line with national and international guidelines •To provide a nurse led vaccination clinic for patients with IBD •To ensure that all patients with IBD have equal access to Shingrix Methods We negotiated with the pharmacy department to ensure all patients on JAK inhibitors have access to Shingrix vaccination at no cost to the patient. A business case was submitted to the Mercy University Hospital Drugs and therapeutics board. Vaccination protocol was designed with key stakeholders, which was then communicated to all team members. A weekly nurse led vaccination clinic was established in October 2023. Vaccination administration given in two consecutive doses as per guidelines. Results Since the launch of the weekly nurse led vaccination clinic, 196 vaccinations have been administered to date, with 98 patients fully vaccinated with Shingrix (non-live vaccination). JAK inhibitor treatment can now be commenced without delay, resulting in increased patient satisfaction with the IBD service. Of the vaccinated patients, to date, none have developed Shingles. Conclusion This nurse led project has ensured that patients with IBD who require treatment with a JAK inhibitor can now avail of vaccination in line with national and international guidelines resulting in increased patient service satisfaction and reassurance following vaccination with nil adverse effects experienced from patients. References T Kucharzik, P Ellul, T Greuter, J F Rahier, B Verstockt, C Abreu, A Albuquerque, M Allocca, M Esteve, F A Farraye, H Gordon, K Karmiris, U Kopylov, J Kirchgesner, E MacMahon, F Magro, C Maaser, L de Ridder, C Taxonera, M Toruner, L Tremblay, M Scharl, N Viget, Y Zabana, S Vavricka, on behalf of the European Crohn’s and Colitis Organisation [ECCO], ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease, Journal of Crohn's and Colitis, Volume 15, Issue 6, June 2021, Pages 879–913, https://doi.org/10.1093/ecco-jcc/jjab052

Abstract Background The National Bowel Screening Program (Bowelscreen), a nationwide initiative program, aims to provide direct access to those aged 55-74 (currently 59-69) for colonoscopy assessment deemed high risk for colorectal cancer via positive faecal immunochemical test (FIT). Inflammatory Bowel Disease (IBD) follows a bimodal distribution of onset with European studies reporting 10-15% diagnosis after age 60. Limited published research exists on IBD incidence in Ireland via FIT-based population screening and associated outcomes. We aim to dtermine incidence rates/severity of incident IBD cases found via FIT-based colorectal screening programme and hRetrospective review was conducted of all index colonoscopes conducted in FIT positive screening participants (aged 59-69) in multiple Irish centres between 2015-2024. Inclusion criteria: histological diagnosis of colitis. Parameters measured: distribution of colitis, histology, clinical sequalae/IBD history, faecal calprotectin (FCP) and treatment escalation based on screening colonoscopyow often screening colonoscopy is performed for patients with known IBD and positive FIT. Methods Retrospective review was conducted of all index colonoscopes conducted in FIT positive screening participants (aged 59-69) in multiple Irish centres between 2015-2024. Inclusion criteria: histological diagnosis of colitis. Parameters measured: distribution of colitis, histology, clinical sequalae/IBD history, faecal calprotectin (FCP) and treatment escalation based on screening colonoscopy. Results 203/8070 (2.52%) of index screening colonoscopies analysed reported endoscopic diagnosis of colitis. 105/8070 (1.3%) satisfied diagnostic criteria for classic IBD (65.7% UC; 34.2% Crohn’s), of which the majority were new diagnosis (73.3%). 32% cases of segmental colitis associated with diverticulosis (SCAD) were identified. 21% cases of NSAID induced colitis were identified. UC Colitis distribution: 18.8% pancolitis, 38.4% proctitis and 42.8% left-sided. Crohn’s distribution: 8.3% small bowel solely; 89% colonic and 2.7% mixed. 48% reported symptoms at endoscopy. Median FCP following diagnostic colonoscopy was 216.5μg/g. 10% of newly diagnosed IBD patients required biologic escalation. Conclusion Incidental diagnosis of colitis occurs in 3% of FIT-positive screening participants in a population based screening programme with new diagnoses of IBD including UC, Crohn’s and SCAD requiring treatment. This is a novel, unintended benefit to FIT-based population screening.

Abstract Background Point of care ultrasound is a real-time, non-invasive imaging modality used across many disciplines for several years, including in Inflammatory Bowel Disease (IBD) patients in central Europe. However, it is only recently beginning to be introduced in an Irish context. This study aims to explore the perspectives of key stakeholders in IBD in Ireland, towards the introduction of point of care ultrasound (PoCUS) amongst IBD patients. The secondary aim is to clarify if key stakeholders are supportive of nurse performed PoCUS in IBD if a referral pathway was to become available in an Irish context. Methods A quantitative cross sectional, descriptive online survey was developed to collect anonymous responses from key stakeholders in the IBD clinical care context in Ireland. The email inviting potential respondents to consider participation in the survey was distributed by two professional bodies – The Irish Society of Gastroenterology and Inflammatory Bowel Disease Nurses Association of Ireland. Analysis included a descriptive modelling of the data using logistic regression. Results In completing the survey, 25% of respondents confirmed that they had an ultrasound service for IBD patients while 44% (n=42) have future plans to develop one. Among the surveyed doctors, only 9% (n=9) have undergone training in PoCUS, while 79% of all respondents express intentions to pursue training or are open to considering it in the future. On average, respondents disagreed that PoCUS will replace Colonoscopy and MRI in the future, with a mean score of 2.47 (SD 1.24). Doctors and nurses perceive having access to PoCUS as important for patient outcome and quality of care, mean 4.06 (SD 1.02). Overall, 51% (n=48) of respondents reported having no fears or reservations associated with using PoCUS in clinical practice. Both doctors and nurses exhibited positive attitudes towards nurse-led PoCUS in IBD, highlighting its perceived cost effectiveness, as evidenced by a mean score of 4.38 (SD 1.01). Conclusion Key findings highlight a majority of respondents have plans to develop a PoCUS service and undertake training to improve quality of care for patients with IBD. The vast majority of respondents support the introduction of nurse performed PoCUS in the Irish setting. References Dolinger, M. Kayal, M. Intestinal Ultrasound Is the Ideal Patient-Centric, Point-of-Care Tool for Clinical Decision Making in the Inflammatory Bowel Disease Practice, Crohn's & Colitis 360, Volume 5, Issue 3, July 2023, otad029, available at: https://doi.org/10.1093/crocol/otad029.

Abstract Background 8-weekly dosing regimen of ustekinumab in the treatment of moderate-to-severe Inflammatory Bowel Disease (IBD) is the current standard of care. Accelerated 4-weekly dosing has been suggested to be efficacious, however not licensed, in ‘non-responders’. The aim of this study is to determine how 4-weekly accelerated dosing regimen in ustekinumab drug levels correlate with response to treatment in patients with IBD. Methods Patients for inclusion were identified retrospectively utilising online prescription records at Mercy University Hospital, Cork. Inclusion criteria consisted of IBD patients commenced on ustekinumab with a treatment duration of at least 6 months. Participants were separated into 4-weekly and 8-weekly treatment groups. Faecal calprotectin (FCP) levels/ustekinumab drug levels were recorded from the 12-week check in post initiation and at the 2nd assessment. Symptoms were scored at these visits and further quantified using the Harvey Bradshaw index for Crohn’s Disease and the partial mayo score for Ulcerative Colitis. Results 101 patients at the Mercy University Hospital Cork were identified utilising a database of prescriptions and physical charts (4-weekly: 27; 8-weekly: 74). A statistically significant decrease in FCP levels at 2nd assessment was noted in patients with 4-weekly dosing (p=0.028). There was no statistically significant relationship between dosing interval and symptoms (p=0.735). Individual patient factors including age, gender, type of IBD, and concurrent IBD medications did not have a statistically significant effect on faecal calprotectin levels or symptoms. Conclusion The greater percentage decrease in faecal calprotectin provides objective evidence supporting the escalated dosing interval at the Mercy University Hospital IBD centre. However, further study is necessary to justify increasing the dosing interval for all patients treated with ustekinumab for IBD.

Viruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted by previous sequencing requirements that necessitated the amplification of starting nucleic acids. In this study, we performed an original longitudinal analysis of 40 healthy control, 19 Crohn’s disease, and 20 ulcerative colitis viromes over three time points without an amplification bias, which revealed and highlighted the interpersonal individuality of the human gut virome. In contrast to a 16 S rRNA gene analysis of matched samples, we show that α- and β-diversity metrics of unamplified viromes are not as efficient at discerning controls from patients with inflammatory bowel disease. Additionally, we explored the intrinsic properties of unamplified gut viromes and show there is considerable interpersonal variability in viral taxa, infrequent longitudinal persistence of intrapersonal viruses, and vast fluctuations in the abundance of temporal viruses. Together, these properties of unamplified faecal viromes confound the ability to discern disease associations but significantly advance toward an unbiased and accurate representation of the human gut virome.

A colonoscopy was performed in a 65-year-old asymptomatic patient with a positive faecal immunochemical test. Their only medical history was well-controlled asthma. The colonoscopy was performed by an experienced bowel cancer screening endoscopist. The examination found a lumen-filling lesion in the ascending colon (figure 1) just downstream to the ileocaecal valve. The lesion was hard to touch and biopsies were taken. The appearance was compatible with an eroding submucosal lesion. The endoscopist informed the patient of the likely diagnosis of cancer, and requested urgent imaging. Figure 1 Endoscopic view of ascending colon. The case was discussed in the Complex Polyp …

Endoscopic resection of premalignant lesions from the colorectum can prevent the development of colorectal cancer (CRC). This is largely dependent on the quality of colonoscopy performed and can be divided into 3 areas: lesion detection, lesion resection, and appropriate surveillance. Quality assurance programs and colonoscopy quality indicators have been developed to ensure that endoscopists operate within accepted standards of care.1Rees C.J. Thomas Gibson S. Rutter M.D. et al.UK key performance indicators and quality assurance standards for colonoscopy.Gut. 2016; 65: 1923-1929Crossref PubMed Scopus (187) Google Scholar,2Kaminski M.F. Thomas-Gibson S. Bugajski M. et al.Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative.United European Gastroenterol J. 2017; 5: 309-334Crossref PubMed Scopus (114) Google Scholar Established key performance indicators (KPIs) for lesion detection include adequate bowel preparation, cecal intubation rates of >90%, withdrawal times >6 minutes, and adenoma detection rates ≥25%. Adenoma detection rate has been shown to be inversely associated with the risk of postcolonoscopy interval CRC.3Corley D.A. Jensen C.D. Marks A.R. et al.Adenoma detection rate and risk of colorectal cancer and death.N Engl J Med. 2014; 370: 1298-1306Crossref PubMed Scopus (1277) Google Scholar Several societal guidelines exist for adequate surveillance intervals and are adjusted as evidence accumulates to strike a balance between protection from CRC and the burden of too-frequent examinations.4Rutter M.D. East J. Rees C.J. et al.British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines.Gut. 2020; 69: 201-223Crossref PubMed Scopus (173) Google Scholar The resection of large colorectal lesions by the use of cold snare polypectomy, EMR, and endoscopic submucosal dissection presents higher-risk aspects of colonoscopy, and although competency measures have been developed,5Gupta S. Bassett P. Man R. et al.Validation of a novel method for assessing competency in polypectomy.Gastrointest Endosc. 2012; 75: 568-575Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar less emphasis has been placed on the development of performance indicators for polyp resection, particularly in bowel cancer screening cohorts. The objective of endoscopic resection is to completely, safely, and efficiently remove neoplastic tissue, obviating the need for surgery. Incomplete removal is thought to account for approximately 19% of interval CRCs.6Robertson D.J. Lieberman D.A. Winawer S.J. et al.Colorectal cancers soon after colonoscopy: a pooled multicohort analysis.Gut. 2014; 63: 949-956Crossref PubMed Scopus (318) Google Scholar Assessing complete resection as a quality metric, however, has challenges. Initial resection is assessed optically by the endoscopist, who may or may not use adjunctive techniques to identify and treat residual tissue. Intraprocedural bleeding occurs in ≤11% of cases and often impairs visualization of the resection field.7Burgess N.G. Metz A.J. Williams S.J. et al.Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.Clin Gastroenterol Hepatol. 2014; 12: 651-661.e1-3Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar This makes assessment of complete resection more difficult and has been shown to be associated with polyp recurrence.7Burgess N.G. Metz A.J. Williams S.J. et al.Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.Clin Gastroenterol Hepatol. 2014; 12: 651-661.e1-3Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar Often at follow-up no identifiable scar is found, which can make differentiating recurrence from a new polyp in the same segment difficult, particularly over longer surveillance intervals. The British Society of Gastroenterology recommends tattooing of all lesions ≥20 mm outside the cecum or rectum with a clear description of the tattoo site relative to the resected lesion in the endoscopy report so that there is no ambiguity at endoscopic follow-up.1Rees C.J. Thomas Gibson S. Rutter M.D. et al.UK key performance indicators and quality assurance standards for colonoscopy.Gut. 2016; 65: 1923-1929Crossref PubMed Scopus (187) Google Scholar In terms of safety, the 2 most significant adverse events associated with colonoscopy, namely, perforation and bleeding, occur predominantly during therapeutic polypectomy rather than during diagnostic procedures. Some series report a 2% risk of delayed bleeding and a 1% perforation risk.8Amato A. Radaelli F. Correale L. et al.Intra-procedural and delayed bleeding after resection of large colorectal lesions: the SCALP study.United European Gastroenterol J. 2019; 7: 1361-1372Crossref PubMed Scopus (7) Google Scholar With such rare event rates, defining thresholds and targets for avoiding adverse events is difficult. In this edition of Gastrointestinal Endoscopy, Meulen et al9Meulen L.W.T. van der Zander Q.E.W. Bogie R.M.M. et al.Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.Gastrointest Endosc. 2021; 94: 1085-1095Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar investigate the quality of endoscopic management for large, nonpedunculated colorectal polyps (LNPCPs) within the Dutch Bowel Cancer Screening Programme. The investigation comprised 2 related but separate substudies. The first retrospectively examined the prevalence and characteristics of LNPCPs over a 35-month period from a national cohort. These data lacked histologic and follow-up data. Therefore, a second substudy prospectively examined polypectomy effectiveness and safety over 18 months using screening data from 5 Dutch endoscopy units, none of which were tertiary referral centers. Polypectomy performance was determined by technical success (macroscopically complete resection), clinical success (no neoplasia at 12 months), recurrence rates (determined by optical examination of the scar), surgical referral rates, and surveillance adherence. Safety was determined by adverse event rates including postpolypectomy syndrome, acute bleeding (<24 hours), delayed bleeding, and deep mural injury. Endoscopists were stratified according to their experience. In the national cohort, the prevalence of patients having at least 1 LNPCP was 8%. The vast majority of patients underwent EMR (91%), with only 1% undergoing endoscopic submucosal dissection. The overall technical and clinical success rates were both 87% and were noted to decrease with increasing LNPCP size. The technical success rate fell to 74% for lesions ≥40 mm. Nonadherence to surveillance guidelines was notable, with 31% of patients undergoing delayed surveillance, although it is not clear whether patient, clinical, and/or service factors were primarily responsible. This may have accounted for a lower clinical success rate resulting from the lost opportunity to treat possible early recurrence. Overall recurrence rates of 22% for piecemeal and 8% for en bloc resection after 12 months were reported. Recurrence rates increased with increasing LNPCP size. Notably, no adjuvant techniques to endoscopic resection were performed aimed at preventing recurrence, such as thermal ablation of the defect margins. Overall adverse event rates were low, occurring in 14 of 266 procedures (5%) and included postpolypectomy syndrome (0.4%), acute bleeding (1%), and delayed bleeding (4%). There were no reports of deep mural injury or full-thickness perforation. Variations between lesion size and adverse event rate did not reach statistical significance. The overall rate of referral for surgical management as primary therapy of noninvasive LNPCPs was 7%, but there were clear variations between centers, ranging from 4% to 10%. Experienced and dedicated endoscopists were less likely to refer large polyps for surgery and had higher technical success rates than nonexperienced and nondedicated endoscopists. The gap in quality between endoscopists at expert centers and those at the Dutch Bowel Cancer Screening Programme clearly widened for lesions ≥30 mm. The British Society of Gastroenterology guidelines for the management of LNPCPs propose KPIs in the domains of optimal decision making, endoscopic skill, safety, timeliness, and volume of procedures.1Rees C.J. Thomas Gibson S. Rutter M.D. et al.UK key performance indicators and quality assurance standards for colonoscopy.Gut. 2016; 65: 1923-1929Crossref PubMed Scopus (187) Google Scholar Currently, no standards are defined in the domains of optical decision making as measured by surgery rate, time from referral to definitive therapy, and minimum number of procedures per endoscopist per year. Endoscopic skill as measured by recurrence and/or residual polyp at 12 months has a minimum standard of <10% and an aspirational standard of <5%. EMR safety as measured by perforation rate and postprocedure bleeding rate has minimal standards defined as <2% and <5%, respectively. The study by Meulen et al 9Meulen L.W.T. van der Zander Q.E.W. Bogie R.M.M. et al.Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.Gastrointest Endosc. 2021; 94: 1085-1095Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar demonstrated that the minimum safety standards for polypectomy were achieved; however, the cumulative recurrence rate after 12 months in the regional Dutch cohort was 16%, above the proposed KPI of <10%. The study therefore suggests that the real-world management of LNPCPs does not match the outcomes achieved in other expert centers. The challenge is this: How can this gap be bridged? Outcomes in polypectomy can be improved by focusing on individual, unit, and regional performance. From an individual endoscopist’s perspective, a standardized approach to polyp assessment and optical diagnosis that uses recognized systems such as Paris, NBI International Colorectal Endoscopic, and Japan NBI Expert Team classifications will allow lesions to be accurately characterized and will facilitate consistent decision making in the management of LNPCPs. The use of standardized scoring systems such as the Size/Morphology/Site/Access score10Gupta S. Miskovic D. Bhandari P. et al.A novel method for determining the difficulty of colonoscopic polypectomy.Frontline Gastroenterol. 2013; 4: 244-248Crossref PubMed Google Scholar for determining polypectomy difficulty allows an individual to decide whether a polyp they are considering resecting is beyond their current competency level. Incorporating these scores into endoscopy reporting systems may help establish their use in daily practice, enhance the decision-making process, and allow for more standardized comparisons of quality metrics. Defined regional and national referral pathways that facilitate the management of polyps by endoscopists with the appropriate expertise should be encouraged and can be achieved through complex polyp multidisciplinary team meetings. This approach may raise concerns over centralization and deskilling, but not every polypectomy needs to be or can be performed at a specialist center. There will remain considerable scope for endoscopists in nonspecialist centers to perform safe and complete polyp resection and to develop their skill set. It is, however, crucial for endoscopists to recognize their limitations, which are multifactorial and are not limited to technical skill level. Considerations include unit capacity and adequate time for the procedure, availability of equipment, appropriate skill mix of the endoscopy team, and availability of anesthetic and surgical expertise. Formal assessment of technical skills in polypectomy can be achieved by use of a Direct Observation of Polypectomy Skills (DOPyS) tool.5Gupta S. Bassett P. Man R. et al.Validation of a novel method for assessing competency in polypectomy.Gastrointest Endosc. 2012; 75: 568-575Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar A structured approach to training using DOPyS assessments can determine what level of polyp complexity based on the Size/Morphology/Site/Access score is safe for an individual endoscopist to perform and in turn stratify referral to specialist centers where appropriate. Training and assessments would ideally take place within regional polyp referral networks. As endoscopists’ skills develop they can progress to performing more complex polypectomies. Whereas the DOPyS tool is used to assess individual competency at 1 point in time, polypectomy KPIs are required to audit performance over a period of time to ensure minimal standards are being met and aspirational targets are continually worked toward. Given the increasing demand for polypectomy generated through both symptomatic and screening colonoscopy, a stronger emphasis must be placed on defining clear quality metrics for endoscopic polypectomy, helping to measure individual, departmental, and regional performance. The DOPyS tool measures the competency of an endoscopist at 1 point in time. Well-defined KPIs for polypectomy will enable performance over a period of day-to-day practice to be measured and for suboptimal performance to be identified and proactively addressed. Therapeutic endoscopy, in particular endoscopic resection of LNPCPs, is an increasingly significant subspecialty area within endoscopy. Dedicated fellowships within expert centers are becoming a standard requirement for those who wish to train in and practice advanced endoscopic resection. Advanced fellowships facilitate mentorship and training to competency and also strengthen working in collaborative networks. For polypectomy standards to improve globally, aspiring endoscopists should be encouraged to pursue advanced training so the skills and knowledge learned can be incorporated into local practice to improve performance and ultimately patient care. All authors disclosed no financial relationships. Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohortGastrointestinal EndoscopyVol. 94Issue 6PreviewWith the introduction of the national bowel cancer screening program, the detection of sessile and flat colonic lesions ≥20 mm in size, defined as large nonpedunculated colorectal polyps (LNPCPs), has increased. The aim of this study was to examine the quality of endoscopic treatment of LNPCPs in the Dutch screening program. Full-Text PDF Open Access

Objective The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. Design Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn’s disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). Results Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. Conclusion The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.

Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease. A randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 ± 6.5 years and Body Mass Index of 28.9 ± 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing. Improved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41mls/kg/min; post-intervention: 46.01mls/kg/min; p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase; p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the α- and β-diversity of gut microbiota and associated metabolic pathways were evident. Moderate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects. The study was registered at ClinicalTrials.gov; Trial number: NCT02463916 .

BACKGROUND AND AIMS:Alterations in short chain fatty acid metabolism, particularly butyrate, have been reported in inflammatory bowel disease, but results have been conflicting because of small study numbers and failure to distinguish disease type, activity or other variables such as diet. We performed a comparative assessment of the capacity of the microbiota for butyrate synthesis, by quantifying butyryl-CoA:acetate CoA-transferase [BCoAT] gene content in stool from patients with Crohn's disease [CD; n = 71], ulcerative colitis [UC; n = 58] and controls [n = 75], and determined whether it was related to active vs inactive inflammation, microbial diversity, and composition and/or dietary habits.METHODS:BCoAT gene content was quantified by quantitative polymerase chain reaction [qPCR]. Disease activity was assessed clinically and faecal calprotectin concentration measured. Microbial composition was determined by sequencing 16S rRNA gene. Dietary data were collected using an established food frequency questionnaire.RESULTS:Reduced butyrate-synthetic capacity was found in patients with active and inactive CD [p < 0.001 and p < 0.01, respectively], but only in active UC [p < 0.05]. In CD, low BCoAT gene content was associated with ileal location, stenotic behaviour, increased inflammation, lower microbial diversity, greater microbiota compositional change, and decreased butyrogenic taxa. Reduced BCoAT gene content in patients with CD was linked with a different regimen characterised by lower dietary fibre.CONCLUSIONS:Reduced butyrate-synthetic capacity of the microbiota is more evident in CD than UC and may relate to reduced fibre intake. The results suggest that simple replacement of butyrate per se may be therapeutically inadequate, whereas manipulation of microbial synthesis, perhaps by dietary means, may be more appropriate.

BACKGROUND:Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection.METHODS:The study involved 10 patients with recurrent C. difficile infection, nine of whom received transplants from individual donors and one who received a donor unit from a stool bank (OpenBiome).RESULTS:All individuals demonstrated enduring post-transplant resolution of C. difficile- associated diarrhoea. Faecal microbiota diversity of recipients significantly increased, and the composition of the microbiota resembled that of the donor. Patients with C. difficile infection exhibited significantly lower faecal levels of secondary/ bile acids and higher levels of primary bile acids. Levels of secondary bile acids were restored in all transplant recipients, but to a lower degree with the OpenBiome transplant. The abundance increased of bacterial genera known from previous studies to confer resistance to growth and germination of C. difficile. These were significantly negatively associated with primary bile acid levels and positively related with secondary bile acid levels. Although reduced levels of the short chain fatty acids, butyrate, propionate and acetate, have been previously reported, here we report elevations in SCFA, pyruvic and lactic fatty acids, saturated, ω-6, monounsaturated, ω-3 and ω-6 polyunsaturated fatty acids (PUFA) in C. difficile infection. This potentially indicates one or a combination of increased dietary FA intake, microbial modification of FAs or epithelial cell damage and inflammatory cell recruitment. No reversion to donor FA profile occurred post-FMT but ω-3 to ω-6 PUFA ratios were altered in the direction of the donor. Archaeal metabolism genes were found in some samples post FMT.CONCLUSION:A consistent metabolic signature was identified in the post-transplant microbiota, with reduced primary bile acids and substantial restoration of secondary bile acid production capacity. Total FA levels were unchanged but the ratio of inflammatory to non-inflammatory FAs decreased.

Figure 1.Longitudinal Comparison of Patient Microbiome Following RBX2660 Treatment and Placebo Treatment using Kullback-Leibler (KL) Divergence Analysis.KL divergence analysis was used to compare microbiota populations stratified by blinded treatment: active (Group A+C) vs placebo (Group B), outcome (success vs failure), and time (baseline, 7 days, 30 days post 2 nddose).Yellow shading corresponds to higher KL divergence in the pairwise comparison.The plot suggests that successful treatment following at least one dose of RBX2660 is associated with a change in microbiome diversity at 7 and 30 days that is greater than change seen in patients with failed active treatment or placebo treatment.

It is widely known that there have been improvements in patient care and an increased incidence of Inflammatory Bowel Disease (IBD) worldwide in recent decades. However, less well known are the phenotypic changes that have occurred; these are discussed in this review. Namely, we discuss the emergence of obesity in patients with IBD, elderly onset disease, mortality rates, colorectal cancer risk, the burden of medications and comorbidities, and the improvement in surgical treatment with a decrease in surgical rates in recent decades.

Purpose of reviewIt is long known that immune and metabolic cascades intersect at various cross-points. More recently, the regulatory influence of the microbiota on both of these cascades has emerged. Advances with therapeutic implications for chronic immunologic and metabolic disorders are examined.Recent findingsDisturbances of the microbiota, particularly in early life, may be the proximate environmental risk factor in socioeconomically developed societies for development of chronic immune-allergic and metabolic disorders, including obesity. Antibiotics and dietary factors contribute to this risk. Multiple microbial signalling molecules mediate host-microbe interactions including bacterial metabolites such as short-chain fatty acids, bile salts and others.SummaryNew strategies for manipulating the composition and metabolic activity of the gut microbiota have emerged and offer a realistic prospect of personalized therapeutic options in immune and metabolic diseases.

This review explores our current understanding of the complex interaction between environmental risk factors, genetic traits and the development of inflammatory bowel disease. The primacy of environmental risk factors is illustrated by the rapid increase in the incidence of the disease worldwide. We discuss how the gut microbiota is the proximate environmental risk factor for subsequent development of inflammatory bowel disease. The evolving fields of virome and mycobiome studies will further our understanding of the full potential of the gut microbiota in disease pathogenesis. Manipulating the gut microbiota is a promising therapeutic avenue.

Purpose of reviewAlthough many studies of the microbiota have been specific to the colonic or faecal microbiota, several studies are relevant to or directly address the small bowel microbiota in health and disease. A selection of recent landmark findings is addressed here.Recent findingsThe complexity of host-microbe interactions is confirmed by unfolding evidence for signalling networks including microbe-macrophage-neuronal communication and several examples of diet-microbe-host metabolic exchanges. The contribution of the microbiota to several disorders, including celiac disease and inflammatory bowel disease, is increasingly evident and the importance of drug-bug interactions has been clarified.SummaryDespite difficulty accessing the small bowel microbiota, there is growing evidence for its role in development, homeostasis and a diversity of diseases.