Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.

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.

Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ß-diversity of gut microbiota and associated metabolic pathways were evident. CONCLUSIONS: 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. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov; Trial number: NCT02463916 .

When is feeding via a percutaneous endoscopic gastrostomy indicated?

PURPOSE OF REVIEW: This review addresses current controversies regarding appropriate indications for percutaneous endoscopic gastrostomy (PEG) insertion. We address specific indications, namely, dementia, stroke, aspiration, motor neurone disease/amyotrophic lateral sclerosis, and head and neck cancer. We recommend practical strategies for improving patient selection. RECENT FINDINGS: There is now a general consensus in the United States that PEG feeding does not benefit patients with advanced dementia. 'Early' PEG insertion following stroke is similarly of no benefit. It is currently unclear whether patients with amyotrophic lateral sclerosis and head and neck tumors should have PEG or radiologically inserted gastrostomy. SUMMARY: Decisions relating to PEG insertion remain difficult. The gastroenterologist, working as a member of a multidisciplinary nutrition team, needs to take a lead role in this regard, rather than functioning as a technician.

The small bowel microbiota.

PURPOSE OF REVIEW: Although 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 FINDINGS: The 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. SUMMARY: Despite difficulty accessing the small bowel microbiota, there is growing evidence for its role in development, homeostasis and a diversity of diseases.

Assessment of the value of gastroenterologists' activity in the outpatient setting: applying the "Moneyball" approach to clinical care.

BACKGROUND: With the emergence of alternative payment systems replacing the traditional funding models, the value of physician activity is scrutinized more closely. Attempts have been made to quantify the value of endoscopists' activity; there is little in the medical literature describing gastroenterologists' value in the outpatient setting. AIMS: To characterize the value of clinical activity of gastroenterologists in the outpatient setting. METHODS: The value of clinical activity of ten gastroenterologists in an academic medical center was estimated. Value was defined as Q (quality of clinical care) divided by TA (duration of outpatient visit adjusted for complexity level); TA served as a surrogate measure of the cost of the clinician's services. Medical records of each patient's clinical visit were reviewed and graded independently by three staff gastroenterologists; each reviewer was blinded to the identity of the physician and to other reviewers' scores. RESULTS: Over consecutive weeks, the clinical records of 307 patients who were seen by ten gastroenterologists were reviewed and graded for quality (Q) and complexity (C); the duration of each visit (T) was recorded. Each physician saw a mean of 31 patients; mean physician value varied from 0.28 to 0.87. More senior physicians demonstrated higher levels of value. CONCLUSION: Measurement of the value of clinical activity represents an important component of gastroenterologists' performance. There was a threefold variation among physician levels of value with more experienced clinicians demonstrating higher value levels. Further studies will be required to more clearly define valid metrics for physician value.

Measuring the value of endoscopic retrograde cholangiopancreatography activity: an opportunity to stratify endoscopists on the basis of their value.

INTRODUCTION: As finite healthcare resources come under pressure, the value of physician activity is assuming increasing importance. The value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Even though some attempts have been made to quantify the value of clinician activity, there is little in the medical literature describing the importance of endoscopists' activity. This study aimed to characterize the value of endoscopic retrograde cholangiopancreatography (ERCP) performance of five gastroenterologists. PATIENTS AND METHODS: We carried out a retrospective-prospective cohort study using the databases of patients undergoing ERCP between September 2014 and March 2017. We collected data from 1070 patients who underwent ERCP comparing value among the ERCPists at index ERCP. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure, T is the duration of procedure and C is the adjusted for complexity level. Quality and complexity were derived on a 1-4 Likert scale on the basis of American Society for Gastrointestinal Endoscopy criteria; time was recorded (in min) from intubation to extubation. Endoscopist time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized. RESULTS: In total, 590 procedures were analysed: 465 retrospectively over 24 months and 125 prospectively over 6 months. There was a 32% variation in the value of endoscopist activity in a more substantial retrospective cohort, with an even more considerable 73% variation in a smaller prospective arm. CONCLUSION: In an analysis of greater than 1000 ERCPs by a small cohort of experienced ERCPists, there was a wide variation in the value of endoscopist activity. Although the precision of estimating procedural costs needs further refinement, these findings show the ability to stratify ERCPists on the basis of the value their activity. As healthcare costs are scrutinized more closely, such value measurements are likely to become more relevant.

Determinants of Reduced Genetic Capacity for Butyrate Synthesis by the Gut Microbiome in Crohn's Disease and Ulcerative Colitis.

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.

The Changing Phenotype of Inflammatory Bowel Disease.

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.

Endoscopic evaluation in diagnosis and management of inflammatory bowel disease.

Endoscopy is a keystone in the management of patients with inflammatory bowel disease (IBD). It is the fundamental diagnostic tool for IBD, and can help discern between ulcerative colitis and Crohn's disease. Endoscopic assessment provides an objective end point in clinical trials, and identifies patients in clinical practice who may benefit from treatment escalation and may assist risk stratification in patients seeking to discontinue therapy. Recent advances in endoscopic assessment of patients with IBD include video capsule endoscopy, and chromoendoscopy. Technological advances enable improved visualization and focused biopsy sampling. Endoscopic resection and close surveillance of dysplastic lesions where feasible is recommended instead of prophylactic colectomy.

The microbiota in inflammatory bowel disease.

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.

Gut microbiota and obesity: role in aetiology and potential therapeutic target.

Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gut microbiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gut microbiota in weight regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metabolism, found in obesity-related disorders. Modulation of the gut microbiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal.

Malignancy-associated gastroparesis: an important and overlooked cause of chronic nausea and vomiting.

A 69-year-old woman was referred to a gastroenterology clinic with a 1-year history of protracted nausea and postprandial vomiting. She had a background of gastro-oesophageal reflux disease, irritable bowel syndrome and chronic obstructive pulmonary disease with a significant smoking history. Her laboratory work-up including autoimmune screen, coeliac serology and synacthen test were unremarkable. Upper gastrointestinalendoscopy and CT imaging ruled out mucosal and obstructive causes. Gastric emptying studies demonstrated a delayed gastric emptying consistent with diagnosis of gastroparesis. Concurrently, she underwent a CT of the thorax for unresolved consolidation on her chest X-ray. This revealed a locally advanced primary lung carcinoma. In this context, with all other causes excluded, her gastroparesis was deemed to represent a paraneoplastic phenomenon. Gastroparesis is a frequent, under-recognised and important complication of cancer.

Haemodialysis-induced syncope due to Chiari II malformation.

Spina bifida (SB) is associated with chronic kidney disease as a result of vesicoureteric reflux. A proportion of patients progress to end-stage kidney disease (ESKD). Haemodialysis (HD) is probably the most common modality in ESKD, as intra-abdominal malformations and previous surgery can make peritoneal dialysis more challenging. The Chiari malformations also frequently occur in these patients. We report a case of recurrent syncope induced by HD in a patient with SB and the Chiari II malformation. Sparse data exist on the complications of HD in this patient population and on the approach to the management of dialysis-induced syncope in these individuals.