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A systematic study was performed into the degradation of ziprasidone in simulated postmortem blood. Fifteen potential degradation products not previously reported in the literature were observed. Four resulted from degradation in human blood, whereas the remaining products resulted from reaction with solvents: four from alkaline degradation, four from reaction with acetaldehyde, and three from reaction with acetone. To identify possible degradation products, a liquid chromatograph-diode array detector (LC-DAD) and liquid chromatograph quadrupole-time-of-flight mass spectrometer (LC-QTOF-MS) operating in auto-MS/MS mode were used. It was indicated from red-shifted UV-Vis spectra, accurate mass data, mass fragmentation data, and a deuteration experiment that the site of ziprasidone degradation, in the in vitro blood experiments, was the methylene carbon of the oxindole moiety. The major in vitro blood degradation products were proposed to be E/Z isomers of 3-ethylidene-ziprasidone. Further, another in vitro degradation product in microbially inoculated blood specimens was proposed to be 3-ethyl-ziprasidone. 3-Ethylidene-ziprasidone was hypothesized to form from the reaction of ziprasidone with acetaldehyde derived from the ethanol used to spike ziprasidone into the in vitro blood experiments. Data from two postmortem investigations were available for retrospective reanalysis. Attempts were made to detect degradation products of ziprasidone, but none were found.

From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.

Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined.Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location.Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (β = 3.85% per 10% increase in a postcode's migrant population; P 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance.Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy.

The efficacy of immune checkpoint inhibitors (immunotherapy) is increasingly recognized to be linked to the composition the gut microbiome. Given the high rates of resistance, interventions targeting the gut microbiome are now being investigated for its ability to improve the efficacy of immunotherapy. In light of recently published data demonstrating a strong correlation between the efficacy and toxicity of immunotherapy, there is a risk that efforts to enhance immunotherapy efficacy may be undermined by increases in immune-related adverse events (IrAEs) This is particularly important for microbial interventions aimed at increasing immunotherapy efficacy, with many microbes implicated in tumour response also linked to IrAEs, especially colitis. IrAEs have a profound impact on patient quality of life, causing physical, psychosocial, and financial distress. Here, we outline strategies at the discovery, translational, and clinical research phases to ensure the impact of augmenting immunotherapy efficacy is approached in a manner that considers adverse implications. Adopting these strategies will ensure that our ongoing efforts to overcome immunotherapy resistance are not impacted by unacceptable toxicity.

Fecal microbiota transplantation (FMT) is effective for induction of remission in ulcerative colitis (UC). Diet has potential to augment the efficacy and durability of FMT by encouraging engraftment of transplanted microorganisms. A trial of FMT combined with a defined diet was undertaken as salvage therapy for a 71‐year‐old woman with active steroid‐refractory extensive UC. A multidimensional sulfide‐reducing diet (4‐SURE diet) was commenced followed by single‐donor FMT administered by colonoscopy and then enemas over 7 days. Dietary adherence, clinical evaluation, and stool samples for metagenomic profiling were undertaken at weeks 0, 4, 8, and 24. Colonoscopy was performed 8 weeks post‐FMT. Shotgun metagenomic profiling of the donor fecal suspension was also performed. A rapid clinical response to FMT and 4‐SURE diet was observed with normalization of stool frequency (≤2 motions/day) and resolution of rectal bleeding within 2 weeks. Dietary adherence was excellent. Colonoscopy at week 8 revealed no evidence of active colitis (Mayo endoscopic sub‐score 0) with histology showing no evidence of acute or chronic lamina propria inflammatory cell infiltrate. Sustained clinical and endoscopic remission out to 24 weeks was observed. Metagenomic sequencing confirmed sustained engraftment of beneficial donor microbiota with increased alpha‐diversity and capacity for short‐chain fatty acid production, including Faecalibacterium prauznitzii and Eubacterium hallii. This case report supports the rationale of prescribed diet therapy to support engraftment of donor microbiota following FMT for UC. Further large trials with a diet‐arm control group are needed to evaluate FMT augmented by a defined diet in UC., Durable efficacy and sustained remission to 24 weeks associated with microbial engraftment of induction fecal microbiota transplantation augmented by diet are observed in a patient with refractory ulcerative colitis (UC). Metagenomic sequencing confirmed sustained engraftment of beneficial donor microbiota with increased alpha‐diversity and capacity for short‐chain fatty acid production, including Faecalibacterium prauznitzii and Eubacterium hallii. Mechanistic insights provided by functional microbiome analysis illustrate a synergistic combined approach to microbial manipulation in UC.

There is mounting evidence that microbiome composition is intimately and dynamically connected with host energy balance and metabolism. The gut microbiome is emerging as a novel target for counteracting the chronically positive energy balance in obesity, a disease of pandemic scale which contributes to >70 % of premature deaths. This scoping review explores the potential for therapeutic modulation of gut microbiota as a means of prevention and/or treatment of obesity and obesity-associated metabolic disorders. The evidence base for interventional approaches which have been shown to affect the composition and function of the intestinal microbiome is summarised, including dietary strategies, oral probiotic treatment, faecal microbiota transplantation and bariatric surgery. Evidence in this field is still largely derived from preclinical rodent models, but interventional studies in obese populations have demonstrated metabolic improvements effected by microbiome-modulating treatments such as faecal microbiota transplantation, as well as drawing attention to the unappreciated role of microbiome modulation in well-established anti-obesity interventions, such as dietary change or bariatric surgery. The complex relationship between microbiome composition and host metabolism will take time to unravel, but microbiome modulation is likely to provide a novel strategy in the limited armamentarium of effective treatments for obesity.

Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.

OBJECTIVE While the global prevalence of antibiotic-resistant Helicobacter pylori (H. pylori) is increasing, there is much regional variation, and local data are required to guide eradication therapy. We performed a systematic review and meta-analysis to determine rates of H. pylori antibiotic resistance in Australia and New Zealand. STUDY DESIGN Random effects meta-analysis of data from 15 published studies and three published abstracts reporting prevalence of primary or secondary H. pylori antibiotic resistance in Australasia. DATA SOURCES PubMed, EMBASE, MEDLINE, PROSPERO, and the Cochrane Library were searched until August, 2020. DATA SYNTHESIS Fifteen published studies and three published abstracts were identified; one study was excluded due to high risk of bias. Seventeen studies conducted between 1996 and 2013 were included in the final analysis, 12 reporting primary and five reporting secondary antibiotic resistance. Prevalence of primary resistance was clarithromycin 7.4% (95% confidence interval [CI], 5.3-9.7%), metronidazole 50.0% (95%CI, 23.9-56.1%), fluoroquinolones 3.7% (95%CI, 0.004-14.8%), and both amoxicillin and tetracycline

Background Recommendations for dietary fibre intake in patients with inflammatory bowel disease are highly variable. Despite the potential benefits of prebiotic fibres on the gut microbiome, many patients with inflammatory bowel disease follow a low fibre diet. The present study comprehensively evaluated intakes of total and prebiotic fibres in patients with inflammatory bowel disease, aiming to determine the adequacy of fibre intake and factors that may influence intake. Methods Outpatients with a formal diagnosis of inflammatory bowel disease were recruited to this multicentre cross-sectional study. Habitual dietary fibre intake including prebiotic fibre types was measured using a validated comprehensive nutrition assessment questionnaire. Adequacy of total fibre intake was compared with Australian Nutrient Reference Values. Multiple linear regressions were performed to determine factors influencing fibre intake. Results Of 92 participants, 52% had Crohn's disease, 51% were male and the mean age was 40 years. Overall, only 38% of the cohort consumed adequate total fibre (median 24 g day-1 , interquartile range 18.5-32.9 g day-1 ). Adequate fibre consumption was significantly less common in males than females (21.3% versus 55.6%, P = 0.002). Resistant starch intake (median 2.9 g day-1 , interquartile range 2.1-4.8 g day-1 ) was significantly less than the proposed recommendations (20 g day-1 ). Disease-related factors such as phenotype and disease activity were not found to influence fibre intake. Conclusions Patients with inflammatory bowel disease habitually consume inadequate fibre, particularly prebiotic fibre resistant starch. The potential deleterious effects of low prebiotic intake on the gut microbiome and disease-related outcomes in inflammatory bowel disease are unknown and warrant further research.

Background and Aim Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent or refractory Clostridioides difficile infection (rCDI). Despite inclusion in society guidelines, the uptake of FMT therapy has been variable. Physician and patient attitudes may be a barrier to evidence‐based uptake of therapies; however, data assessing attitudes regarding FMT for rCDI are limited. Methods The South Australian FMT for CDI database prospectively recorded patient outcomes of FMT for CDI from August 2013 to January 2019. A total of 93 consecutive patients who underwent FMT for rCDI in South Australia were invited to participate in a 20‐question survey regarding the patient experience of FMT. All gastroenterologists and infectious disease physicians practicing in South Australia were invited to participate in an online survey comprised of 22 questions that addressed referral experience, indications for referral, perceived risks, and regulation and funding. Results Fifty‐four patients (54/93, 58%) returned the survey, of whom 52 (96%) would recommend FMT to others, and 51 (94%) were satisfied with treatment outcome. Fifty physicians returned the online survey (50/100, 50%), of whom 23 (46%) were concerned about disease transmission risk, and 15 (30%) believed that the risk of FMT would outweigh the benefit. Infectious diseases physicians and advanced trainees had significantly greater concern regarding the potential alteration of the microbiome than gastroenterology physicians and advanced trainees (8/17 (47%) vs 6/33 (18%); P = 0.047). Conclusion Despite high levels of patient‐reported satisfaction following FMT, physician‐reported reservations exist and may present a barrier to uptake of this therapy.

The COVID‐19 pandemic, caused by the novel coronavirus SARS‐CoV‐2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS‐CoV‐2 manifests with a severe acute respiratory illness and currently there are insufficient data regarding the virulence of COVID‐19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease (IBD) patients in the context of the COVID‐19 pandemic in the Australasian setting.

Background and Aim Objective monitoring of disease activity is integral to therapeutic decision‐making in inflammatory bowel disease (IBD). Data are sparse on patients' perspectives of tools used to monitor disease activity in IBD. To evaluate patients' perspectives of gastrointestinal ultrasound (GIUS) performed during routine IBD clinical care, along with its impact on IBD‐specific knowledge. Methods Patients with a formal diagnosis of IBD who underwent GIUS at two tertiary IBD services between March 2017 and January 2019 participated in this prospective study. Participants completed a questionnaire measuring the acceptability, tolerability, and usefulness of GIUS using a visual analogue scale (VAS) from 0 (disagree) to 10 (strongly agree). Comparative acceptability of IBD monitoring tools and the impact of GIUS on IBD‐specific knowledge was measured. Results A total of 121 participants completed the questionnaire, with a mean age of 42 years (range 17–78), 54 (45%) males, and 79 (65%) Crohn's disease patients. In the overall population, GIUS was scored as highly acceptable for monitoring IBD (mean 9.20 ± 1.37) compared to colonoscopy (7.94 ± 2.30), stool sampling (8.17 ± 1.96), blood sampling (8.87 ± 1.62), and imaging (8.67 ± 1.60); P, Gastrointestinal ultrasound (GIUS) is being increasingly used for disease monitoring in inflammatory bowel disease; however, patient perceptions of the different modalities available are sparse. This article evaluates patient perceptions, finding that GIUS was preferred to other modalities, and it was also found to have an impact on disease‐related knowledge.

Background and Aim Point‐of‐care ultrasound (POCUS) is a noninvasive alternative to ileocolonoscopy for monitoring disease activity in inflammatory bowel disease (IBD) but is underutilized in practice. Accuracy data are needed to engender clinician confidence in POCUS and increase uptake. The aim of this study was to evaluate the accuracy of POCUS compared to ileocolonoscopy in detecting active disease and extent in patients with IBD. Methods A prospective, blinded study was performed at a single tertiary center in South Australia between May 2017 and May 2018. Consecutive patients with a formal diagnosis of IBD who underwent both POCUS and ileocolonoscopy within 30 days of one another, performed to evaluate IBD disease activity, were eligible for participation. The accuracy of POCUS compared to ileocolonoscopy was assessed using sensitivity, specificity, and Cohen's kappa coefficient analyses. Results A total of 74 patients were included in the final analysis, 35 (47%) of whom had Crohn's disease and 39 (53%) ulcerative colitis; 37 subjects (50%) underwent a POCUS and ileocolonoscopy on the same day. POCUS demonstrated 91% sensitivity and 83% specificity for detecting endoscopically active IBD, correlating with a positive predictive value (PPV) of 89%, a negative predictive value (NPV) of 86%, and a kappa coefficient of 0.74 (88%). POCUS defined disease extent with 87% sensitivity and 81% specificity, correlating with a PPV of 85% and NPV of 83% and a kappa coefficient of 0.70 (85%). Conclusion POCUS is accurate in defining disease activity and extent in IBD compared to ileocolonoscopy. POCUS represents an appealing, noninvasive alternative to ileocolonoscopy for monitoring disease activity in IBD., Point of care ultrasound is incorporated into routine IBD assessment in many European centers, however uptake in Australia has been slow. This article evaluates the accuracy of point of care ultrasound in monitoring disease activity in a local cohort of IBD patients. Point of care ultrasound was found to be accurate for monitoring disease activity and extent in IBD compared to the gold standard, ileocolonoscopy.

ObjectiveFaecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.DesignFor these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.ResultsConsensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development.ConclusionsThese FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.

Background and Aims Inflammatory bowel disease (IBD) is a lifelong disease requiring frequent assessment to guide treatment and prevent flares or progression. Multiple tools are available for clinicians to monitor disease activity; however, there are a paucity of data to inform which monitoring tools are most acceptable to patients. The review aims to describe the available evidence for patient preference, satisfaction, tolerance and/or acceptability of the available monitoring tools in adults with IBD. Methods Embase, Medline, Cochrane Central and Clinical Trials.gov were searched from January 1980 to April 2019 for all study types reporting on the perspectives of adults with confirmed IBD on monitoring tools, where two or more tools were compared. Outcome measures with summary and descriptive data were presented. Results In 10 studies evaluating 1846 participants, monitoring tools included venipuncture, stool collection, gastrointestinal ultrasound, computed tomography, magnetic resonance imaging, wireless capsule endoscopy, barium follow-through and endoscopy. Outcome domains were patient satisfaction, acceptability of monitoring tool and patient preference. Noninvasive investigations were preferable to endoscopy in nine studies. When assessed, gastrointestinal ultrasound was consistently associated with greater acceptability and satisfaction compared with endoscopy or other imaging modalities. Conclusions Adults with IBD preferred noninvasive investigations, in particular gastrointestinal ultrasound, as compared to endoscopy for monitoring disease activity. When assessing disease activity, patient perceptions should be considered in the selection of monitoring tools. Further research should address whether adpoting monitoring approaches considered more acceptable to patients results in greater satisfaction, adherence and ultimately more beneficial clinical outcomes.

In the postmortem environment, some drugs and metabolites may degrade due to microbial activity, even forming degradation products that are not produced in humans. Consequently, underestimation or overestimation of perimortem drug concentrations or even false negatives are possible when analyzing postmortem specimens. Therefore, understanding whether medications may be susceptible to microbial degradation is critical in order to ensure that reliable detection and quantitation of drugs and their degradation products is achieved in toxicology screening methods. In this study, a "simulated postmortem blood" model constructed of antemortem human whole blood inoculated with a broad population of human fecal microorganisms was used to investigate the stability of 17 antidepressant and antipsychotic drugs. Microbial communities present in the experiments were determined to be relevant to postmortem blood microorganisms by 16S rRNA sequencing analyses. After 7 days of exposure to the community at 37°C, drug stability was evaluated using liquid chromatography coupled with diode array detection (LC-DAD) and with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Most of the investigated drugs were found to be stable in inoculated samples and noninoculated controls. However, the 1,2-benzisothiazole antipsychotics, ziprasidone and lurasidone, were found to degrade at a rate comparable with the known labile control, risperidone. In longer experiments (7 to 12 months), where specimens were stored at -20°C, 4°C, and ambient temperature, N-dealkylation degradation products were detected for many of the drugs, with greater formation in specimens stored at -20°C than at 4°C.

Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC).The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy, and effects on microbial endpoints.Adults aged ≥18 y old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins, and avoid specific food additives for 8 wk. The primary outcome was tolerability of diet [100-mm visual analogue scale (VAS) with 100-mm being intolerable]. Secondary exploratory outcomes were self-reported adherence (always adherent ≥76-100%), clinical and endoscopic response (reduction in partial Mayo ≥2 and Mayo endoscopic subscore ≥1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests.Twenty-eight adults with UC [mean (range) age: 42 (22-72) y, 15 females, 3 proctitis, 14 left-sided, and 11 extensive] were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI: 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13 of 28 (46%) and endoscopic improvement in 10 of 28 participants (36%). Two participants (7%) worsened. Fecal excretion of SCFAs increased by 69% (P 0.0001), whereas the proportion of branched-chain fatty acids to SCFAs was suppressed by 27% (-1.34%; 95% CI: -2.28%, -0.40%; P = 0.007). The FRQoL improved by 10 points (95% CI: 4, 16; P 0.001).The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. This trial was registered at https://www.anzctr.org.au (Australian New Zealand Clinical Trials Registry) as ACTRN12619000063112.

The efficacy of immune checkpoint inhibitors (immunotherapy) is increasingly recognized to be linked to the composition the gut microbiome. Given the high rates of resistance, interventions targeting the gut microbiome are now being investigated for its ability to improve the efficacy of immunotherapy. In light of recently published data demonstrating a strong correlation between the efficacy and toxicity of immunotherapy, there is a risk that efforts to enhance immunotherapy efficacy may be undermined by increases in immune-related adverse events (IrAEs) This is particularly important for microbial interventions aimed at increasing immunotherapy efficacy, with many microbes implicated in tumour response also linked to IrAEs, especially colitis. IrAEs have a profound impact on patient quality of life, causing physical, psychosocial, and financial distress. Here, we outline strategies at the discovery, translational, and clinical research phases to ensure the impact of augmenting immunotherapy efficacy is approached in a manner that considers adverse implications. Adopting these strategies will ensure that our ongoing efforts to overcome immunotherapy resistance are not impacted by unacceptable toxicity.

BACKGROUND Measuring food-related quality of life (FRQoL) quantifies the psychosocial impact of eating and drinking. FRQoL and associated factors are not well explored in people with inflammatory bowel disease (IBD), despite IBD being a chronic disease affecting the digestive tract. The present study aimed to characterise and identify any patient or disease-related predictors of FRQoL in individuals with IBD. METHODS Adults with a formal diagnosis of IBD were recruited to a prospective multicentre cross-sectional study between April 2018 and December 2019. Participants completed questionnaires measuring FRQoL (FRQoL-29), clinical disease activity (Harvey Bradshaw Index and Simple Clinical Colitis Activity Index), restrictive eating behaviour (Nine-Item Avoidant/Restrictive Food Intake Disorder Screen), mental health (Depression Anxiety Stress Scale-21) and other patient and disease-related variables. A multivariable regression was performed to identify factors associated with FRQoL. RESULTS One hundred and eight participants completed the questionnaires (n = 39, Crohn's disease; n = 69, ulcerative colitis). The mean FRQoL was 79 (95% confidence interval = 75-84) (poor, 0; superior, 145). Poorer FRQoL was observed in those with restrictive eating behaviour associated with fear of a negative consequence from eating (p

The human gut contains many species of microorganisms, many of which have a role in maintaining good health. The gut microbiota can be affected by diet, diseases and drugs, especially antibiotics. Faecal microbiota transplantation involves transplanting faecal material from a healthy person to a patient, with the aim of treating disease. It is a recommended treatment option for patients with recurrent or refractory Clostridioides difficile as it has a cure rate over 90%. There is evidence that faecal microbiota transplantation can induce remission in ulcerative colitis, however maintenance of remission data are lacking. For other diseases it currently should not be used outside a clinical trial. Stool donors have to be healthy and are screened for a range of diseases. As faecal material is usually transplanted during colonoscopy, the recipient must have bowel preparation before the procedure. Adverse effects are mainly gastrointestinal and usually resolve in the week following transplantation. There are limited data on long-term safety.

The Cochrane IBD Group presented a symposium at Digestive Diseases Week 2018 entitled “Alternative and Complementary Approaches for the Treatment of IBD: Evidence from Cochrane Reviews.” This article summarizes the data presented at this symposium.

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Background Measuring food-related quality of life (FRQoL) quantifies the psychosocial impact of eating and drinking.1 The influences on FRQoL in people with inflammatory bowel disease (IBD) are not well explored, despite IBD being a chronic disease affecting the digestive tract. This study aimed to characterise and identify any patient or disease-related predictors of FRQoL in individuals with IBD. Methods Adults with a formal diagnosis of IBD were recruited to a prospective multi-centre cross-sectional study between April 2018 and December 2019. Participants completed questionnaires measuring FRQoL (IBD-FRQoL-29: minimum/poor 29, maximum/greatest 145), clinical disease activity (active disease: Harvey Bradshaw Index >4 active disease, Simple Clinical Colitis Activity Index >2, restrictive eating behaviour (Nine Item Avoidant/Restrictive Screen: minimum 0, maximum 45), mental health (DASS-21: minimum 0, maximum 126) and other patient and disease-related variables. Results One hundred and eight participants completed the questionnaires. The majority of the cohort had UC (69/108, 64%) and there was almost equal distribution of those with quiescent (48%) and active (52%) disease The mean FRQoL of individuals with IBD was 79 (95% CI 75, 84) (see Figure 1). Poorer FRQoL was seen in those with restrictive eating behaviour associated with fear of a negative consequence from eating (p Conclusion FRQoL in people with IBD is poorer in those with restrictive eating behaviours and clinically active disease. Interestingly, it was greater in those with previous IBD surgery. Further research is required to validate these associations and explore longitudinal effects of poor FRQoL on patient outcomes and potential strategies for prevention or management of impaired FRQoL in IBD. Reference

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

A 19-year-old man presented with acute severe ulcerative colitis. He was taking azathioprine (therapeutic metabolites) and sulphasalazine as well as infliximab with a therapeutic drug level. On day 3 of hydrocortisone therapy, he met day Oxford criteria with >8 bloody stools per day and was given faecal microbiota transplantation and subsequently commenced on dietary therapy combining several strategies—(1) increased intake of fermentable fibres, (2) reduced intake of overall and sulfur-containing protein and (3) restriction of sulfate and sulfite food additives. At week 8 assessment, he was in clinical and endoscopic remission and remained in clinical and endoscopic remission at 12 months.

Background Dietary fiber may influence disease course in individuals with inflammatory bowel disease (IBD), yet there is a paucity of understanding of habitual fiber intakes. Objectives To identify studies measuring fiber intakes of individuals with IBD, compare the adequacy of fiber intakes with that of control groups or respective national dietary guidelines, and examine factors associated with fiber consumption. Methods Five electronic databases—MEDLINE, CINAHL, SCOPUS, PROQUEST, and COCHRANE LIBRARY—were systematically searched, using search terms inflammatory bowel disease, Crohn’s disease, ulcerative colitis, dietary intake, and fiber, until December 2019, with hand searching of reference lists. Primary studies were included if fiber intakes were measured in participants 18 years of age or older, with confirmed IBD, with or without comparison to a control. Results A total of 2105 publications were identified, and 26 met inclusion criteria. Total fiber intake of 4164 participants with IBD ranged broadly (9.9 ± 7.8 g/day to 21.0 ± 10.5 g/day). Most (18/26) used cross-sectional study design, with a large degree of heterogeneity in tools measuring fiber intake. Sixty-six percent of studies comparing participants with IBD with control groups found that participants with IBD consumed significantly less fiber than control subjects. Four studies reported that less than 10% to 21% of IBD participants met their national fiber recommendations. Data conflicted regarding an association between disease type, disease activity, or rate of relapse and fiber intake. Conclusions Individuals with IBD consume less fiber than healthy populations. Fiber intakes are inadequate compared with respective national fiber guidelines. Interpretation of factors associated with fiber intakes were limited by data quality and conflicting results. Future research is required into factors associated with fiber intake and whether increasing fiber intakes can influence disease course and behavior.

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BackgroundVisceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn’s disease (CD); however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes.MethodsBody composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease–related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed.ResultsNinety-seven participants were assessed at baseline (55% male; median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to 3; P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3; 95% CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, –12; 95% CI, –19 to –4.5; P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL.ConclusionVAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution–dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD.

STRUCTURED SUMMARY: • BACKGROUND: Severe and fulminant Clostridioides difficile infection is associated with high mortality rates. While faecal microbiota transplant has been shown to be effective for the treatment of recurrent Clostridioides difficile infection, there is little data on the utility of faecal microbiota transplant in severe or fulminant Clostridioides difficile infection. • AIMS: Compare outcomes of antibiotics plus faecal microbiota transplantation versus antibiotics alone (standard of care) in critically ill patients with severe or fulminant Clostridioides difficile infection. • METHODS: This was a retrospective, matched cohort study in one, urban tertiary academic care center including 48 patients hospitalized with severe or fulminant Clostridioides difficile infection who required care in intensive care unit. • RESULTS: Patients who received faecal microbiota transplantation had a 77% decrease in mortality (OR 0.23, 95%-CI 0.06–0.97) with a number needed to treat of 3 to prevent one death. • CONCLUSIONS: Faecal microbiota transplantation provides mortality benefit over standard of care for severe and fulminant Clostridioides difficile infection and should be considered in critically ill patients.

Background & Aims A ‘Treat to Target' (T2T) approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges. Methods A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated Gastroenterologists' perceptions of T2T in UC. Statistical analysis included logistic regression and Fisher's exact tests. Results Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤1), and 16% in concordant clinical, endoscopic and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, p

Background Dietary misconceptions and behaviours may worsen outcomes of inflammatory bowel disease (IBD). This scoping review aims to examine the dietary beliefs and behaviours of individuals with IBD and identify evidence of food avoidance, dietary restriction or disordered eating and any association with quality of life (QoL). Methodology A systematic search of CINAL, EMBASE, MEDLINE was conducted. Primary, peer-reviewed studies in English examining dietary beliefs and dietary behaviours or diet and quality of life in adults with inflammatory bowel disease were included. Key dietary terminology was pre-defined. Results Twenty-nine studies met inclusion criteria. A range of quantitative self-reported questionnaires (16/29), qualitative interviews (1/29) and mixed methods (7/29) were used to measure dietary beliefs and dietary behaviours. A high prevalence of food avoidance (28–89%) and restrictive dietary behaviours (41–93%) were identified. Factors associated with these behaviours included a diagnosis of CD, perceived active disease, female sex, dietary misinformation, and fears of adverse bowel symptoms. Diet and QoL remains largely unexplored in IBD beyond two recent studies demonstrating impairment of food-related quality of life in IBD. Conclusion A high prevalence of self-reported food avoidance and restrictive dietary behaviour exists in people with IBD. The psychosocial impact of IBD-related dietary behaviour is poorly understood. Validated tools with predefined diet terminology and objective markers of disease activity are required to measure dietary behaviour in future prospective studies, using food-related quality of life as an outcome measure.

SummaryBackground Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. Aim To determine whether FMT is effective and safe for the induction of remission in active UC. Methods Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). Results There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P

Background and Aims The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]. Methods Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.