Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery.

OBJECTIVES: Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. DESIGN: A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. RESULTS: PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. CONCLUSION: The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD. TRIAL REGISTRATION NUMBER: NCT02040922.

Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

OBJECTIVE: Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. DESIGN: A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. RESULTS: Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. CONCLUSIONS: Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. TRIAL REGISTRATION NUMBER: NCT03265002.

Timing of pancreatic enzyme replacement therapy (PERT) in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF suffer with pancreatic exocrine insufficiency, which if left untreated, leads to a poor nutritional status. Pancreatic enzyme replacement therapy (PERT) has been shown to be effective in improving nutritional status and subsequently associated with improved lung function. However, the timings of PERT administration in relation to a meal are subjective and not standardised, meaning that variations in the timing of PERT dosing persist. OBJECTIVES: The primary objective of the review is to compare the efficacy (fat absorption) and effectiveness (nutritional status, lung function and quality of life) of different PERT dosing strategies in terms of timing of administration for treating dietary malabsorption in all individuals with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 24 June 2021. We also searched ongoing trials registers on 09 July 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs), including cross-over RCTs with a minimum washout period of two weeks, and quasi-RCTs of PERT dosing regimens in people (of any age) with CF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and screened the studies identified from the searches. We planned to use GRADE to assess the certainty of evidence for our pre-specified critical outcomes, but we did not identify any eligible studies. MAIN RESULTS: No studies met the eligibility criteria and therefore we did not include any in this review. The excluded studies were either cross-over in design (but lacking a sufficient washout period between treatments) or did not assess the timing of PERT. One study which was terminated early is awaiting assessment pending further information. AUTHORS' CONCLUSIONS: We were unable to determine whether one dosing schedule for PERT is better than another since we identified no eligible RCTs. While the introduction of PERT to people with CF can improve their nutritional status, there are a limited number of studies which address this review question, and none met our eligibility criteria. Since malnutrition and adverse gastrointestinal symptoms remain a common feature in CF, the assessment of the relative performance of dosing schedules may provide evidence to improve outcomes in people with CF who are pancreatic insufficient. Further research is needed to fully evaluate the role of dosing schedules for PERT in fat absorption. Research should also establish reliable outcome measures and minimal clinically important differences. While RCTs with a cross-over design may have advantages over a parallel group design, an adequate washout period between intervention periods is essential.

Design and testing of microbubble-based MRI contrast agents for gastric pressure measurement.

PURPOSE: This work demonstrates specifically tailored microbubble-based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach. METHODS: Enhanced alginate spheres were prepared by incorporating gas-filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach. RESULTS: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas-free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts. CONCLUSION: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes.

Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial.

BACKGROUND: Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using 'follow-on' rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. METHODS: A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400 mg three times a day for 2 weeks, reduced to 200 mg three times a day for a further 2 weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. RESULTS: Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI -28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. CONCLUSION: While 'follow-on' rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.

Chronic diarrhoea in adults: what not to miss.

PURPOSE OF REVIEW: Chronic diarrhoea remains a diagnostic challenge, with numerous causes and few effective symptomatic treatments. This review focuses on new methods for diagnosis of common disorders and alerts readers to rarer causes through a systematic approach to the underlying mechanisms. RECENT FINDINGS: New strategies are emerging to stratify the need for endoscopic investigation. Faecal immunochemical testing, combined with standard blood tests, shows promise in excluding colorectal cancers, adenoma and inflammatory bowel disease, challenging the current use of faecal calprotectin. Serum analysis for markers of bile acid synthesis has been refined, potentially streamlining diagnostic pathways of bile acid malabsorption for those who are unable to access nuclear medicine scans, but the positive predictive value of faecal elastase in low prevalence populations has been questioned. Novel markers such as volatile organic compounds and stool DNA analyses continue to develop. SUMMARY: A systematic approach to investigation of chronic diarrhoea will ensure all relevant causes are considered and minimize the chance of a missed diagnosis. Combination of clinical features with noninvasive testing supports a judicious approach to endoscopic investigations but further innovation will be needed to resolve the diagnostic challenge that diarrhoea poses.

The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls.

Psyllium is a widely used treatment for constipation. It traps water in the intestine increasing stool water, easing defaecation and altering the colonic environment. We aimed to assess the impact of psyllium on faecal microbiota, whose key role in gut physiology is being increasingly recognised. We performed two randomised, placebo-controlled, double-blinded trials comparing 7 days of psyllium with a placebo (maltodextrin) in 8 healthy volunteers and 16 constipated patients respectively. We measured the patients' gastrointestnal (GI) transit, faecal water content, short-chain fatty acid (SCFA) and the stool microbiota composition. While psyllium supplement had a small but significant effect on the microbial composition of healthy adults (increasing Veillonella and decreasing Subdoligranulum), in constipated subjects there were greater effects on the microbial composition (increased Lachnospira, Faecalibacterium, Phascolarctobacterium, Veillonella and Sutterella and decreased uncultured Coriobacteria and Christensenella) and alterations in the levels of acetate and propionate. We found several taxa to be associated with altered GI transit, SCFAs and faecal water content in these patients. Significant increases in three genera known to produce butyrate, Lachnospira, Roseburia and Faecalibacterium, correlated with increased faecal water. In summary, psyllium supplementation increased stool water and this was associated with significant changes in microbiota, most marked in constipated patients.

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition.

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS) via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small- and large-bowel contents after oral challenge. METHODS: We performed a 3-period, cross-over study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/wk) and reported bloating. In parallel, we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500-mL drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects' responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary end point was whether participants had a clinically important symptom response during the 300 minutes after consumption of the drink. RESULTS: More patients with IBS reached the predefined symptom threshold after intake of inulin (13 of 29) or fructose (11 of 29) than glucose (6 of 29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small-bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared with glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P < .05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach the symptom threshold. CONCLUSIONS: Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses after intake of fructose or inulin; patients reported symptoms more frequently after inulin than controls. In patients with a response to inulin, symptoms related to levels of intraluminal gas, but peak gas levels did not differ significantly between responders, nonresponders, or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT01776853.

Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection.

Clostridium difficile (Peptoclostridium difficile) is a common health care-associated infection with a disproportionately high incidence in elderly patients. Disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. Around 20% of patients may suffer recurrent disease, which often requires rehospitalization of patients. C. difficile was isolated from stool samples from a patient with two recurrent C. difficile infections. PCR ribotyping, whole-genome sequencing, and phenotypic assays were used to characterize these isolates. Genotypic and phenotypic screening of C. difficile isolates revealed multiple PCR ribotypes present and the emergence of rifamycin resistance during the infection cycle. Understanding both the clinical and bacterial factors that contribute to the course of recurrent infection could inform strategies to reduce recurrence. (This study has been registered at ClinicalTrials.gov under registration no. NCT01670149.).

Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

Impact of extended Elexacaftor/Tezacaftor/Ivacaftor therapy on the gut microbiome in cystic fibrosis.

BACKGROUND: There is a paucity of knowledge on the longer-term effects of CF transmembrane conductance regulator (CFTR) modulator therapies upon the gut microbiome and associated outcomes. In a pilot study, we investigated longitudinal Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy on the gut microbiota, metabolomic functioning, and clinical outcomes in people with CF (pwCF). STUDY DESIGN: Faecal samples from 20 pwCF were acquired before and then following 3, 6, and 17+ months of ETI therapy. Samples were subjected to microbiota sequencing and targeted metabolomics to profile and quantify short-chain fatty acid composition. Ten healthy matched controls were included for comparison. Clinical data, including markers of intestinal function were integrated to investigate relationships. RESULTS: Extended ETI therapy increased core microbiota diversity and composition, which translated to gradual shifts in whole microbiota composition towards that observed in healthy controls. Despite becoming more similar over time, CF microbiota and functional metabolite compositions remained significantly different to healthy controls. Antibiotic treatment for pulmonary infection significantly explained a relatively large degree of variation within the whole microbiota and rarer satellite taxa. Clinical outcomes were not significantly different following ETI. CONCLUSIONS: Whilst differences persisted, a positive trajectory towards the microbiota observed in healthy controls was found. We posit that progression was predominately impeded by pulmonary antibiotics administration. We recommend future studies use integrated omics approaches within a combination of long-term longitudinal patient studies and model experimental systems. This will deepen our understanding of the impacts of CFTR modulator therapy and respiratory antibiotic interventions upon the gut microbiome and gastrointestinal pathophysiology in CF.

Use of fiber-containing enteral formula in pediatric clinical practice: an expert opinion review.

INTRODUCTION: Children who require enteral nutrition often report gastrointestinal symptoms. There is a growing interest in nutrition formulas that meet nutritional requirements and also maintain gut ecology and function. Fiber-containing enteral formulas can improve bowel function, promote the growth of healthy gut microbiota, and improve immune homeostasis. Nonetheless, guidance in clinical practice is lacking. AREAS COVERED: This expert opinion article summarizes the available literature and collects the opinion of eight experts on the importance and use of fiber-containing enteral formulas in pediatrics. The present review was supported by a bibliographical literature search on Medline via PubMed to collect the most relevant articles. EXPERT OPINION: The current evidence supports using fibers in enteral formulas as first-line nutrition therapy. Dietary fibers should be considered for all patients receiving enteral nutrition and can be slowly introduced from six months of age. Fiber properties that define the functional/physiological properties of the fiber must be considered. Clinicians should balance the dose of fiber with tolerability and feasibility. Introducing fiber-containing enteral formulas should be considered when initiating tube feeding. Dietary fiber should be introduced gradually, especially in fiber-naïve children, with an individualized symptom-based approach. Patients should continue with the fiber-containing enteral formulas they tolerate best.

Tezacaftor/Ivacaftor therapy has negligible effects on the cystic fibrosis gut microbiome.

People with cystic fibrosis (pwCF) experience a range of persistent gastrointestinal symptoms throughout life. There is evidence indicating interaction between the microbiota and gut pathophysiology in CF. However, there is a paucity of knowledge on the potential effects of CF transmembrane conductance regulator (CFTR) modulator therapies on the gut microbiome. In a pilot study, we investigated the impact of Tezacaftor/Ivacaftor dual combination CFTR modulator therapy on the gut microbiota and metabolomic functioning in pwCF. Fecal samples from 12 pwCF taken at baseline and following placebo or Tezacaftor/Ivacaftor administration were subjected to microbiota sequencing and to targeted metabolomics to assess the short-chain fatty acid (SCFA) composition. Ten healthy matched controls were included as a comparison. Inflammatory calprotectin levels and patient symptoms were also investigated. No significant differences were observed in overall gut microbiota characteristics between any of the study stages, extended also across intestinal inflammation, gut symptoms, and SCFA-targeted metabolomics. However, microbiota and SCFA metabolomic compositions, in pwCF, were significantly different from controls in all study treatment stages. CFTR modulator therapy with Tezacaftor/Ivacaftor had negligible effects on both the gut microbiota and SCFA composition across the course of the study and did not alter toward compositions observed in healthy controls. Future longitudinal CFTR modulator studies will investigate more effective CFTR modulators and should use prolonged sampling periods, to determine whether longer-term changes occur in the CF gut microbiome. IMPORTANCE People with cystic fibrosis (pwCF) experience persistent gastrointestinal (GI) symptoms throughout life. The research question "how can we relieve gastrointestinal symptoms, such as stomach pain, bloating, and nausea?" remains a top priority for clinical research in CF. While CF transmembrane conductance regulator (CFTR) modulator therapies are understood to correct underlying issues of CF disease and increasing the numbers of pwCF are now receiving some form of CFTR modulator treatment. It is not known how these therapies affect the gut microbiome or GI system. In this pilot study, we investigated, for the first time, effects of the dual combination CFTR modulator medicine, Tezacaftor/Ivacaftor. We found it had negligible effects on patient GI symptoms, intestinal inflammation, or gut microbiome composition and functioning. Our findings are important as they fill important knowledge gaps on the relative effectiveness of these widely used treatments. We are now investigating triple combination CFTR modulators with prolonged sampling periods.

A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study.

Background: People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods: We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results: We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions: Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrialsgov registration: NCT04006873 (02/07/2019).

A systematic review and meta-analysis on the prevalence of non-malignant, organic gastrointestinal disorders misdiagnosed as irritable bowel syndrome.

Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions-bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I2 statistics. Seven studies (n = 597) estimated the pooled prevalence for BAD as 41% (95% CI 29-54). 17 studies (n = 5068) estimated that of MC as 3% (95% CI 2-4%). Two studies (n = 478) suggested a rate of 4.6% (range: 1.8-6.1%) for PEI. Using breath testing, 26 studies (n = 6700) and 13 studies (n = 3415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44-64%) and 43% (95% CI 23-62%); 36 studies (n = 4630) and 22 studies (n = 2149) estimated that of SIBO as 49% (95% CI 40-57%) with lactulose and 19% (95% CI 13-27%) with glucose. Rates of all conditions were significantly higher than in healthy controls. A significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.

Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis.

BACKGROUND: Most people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health. STUDY DESIGN: Faecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships. RESULTS: pwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed. CONCLUSIONS: Alterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.

Magnetic resonance imaging of the gastrointestinal tract shows reduced small bowel motility and altered chyme in cystic fibrosis compared to controls.

People with cystic fibrosis (CF) experience digestive symptoms but the mechanisms are incompletely understood. Here we explore causes and consequences of slower gastrointestinal transit using magnetic resonance imaging (MRI). Twelve people with CF and 12 healthy controls, matched for age and gender, underwent MRI scans, both fasted and after standardised meals, over 6.5 h. Fasted small bowel motility scores were lower in CF than in controls. No difference in ascending colon chyme T1 was detected. The difference in texture between small bowel and colon contents, seen in health, was diminished in CF. The ascending colon in CF participants had an abnormal appearance compared to controls. MRI offers unique potential to evaluate gut luminal content, colonic mucosa and intestinal motor activity. These new data support the theoretical cycle of desiccation, dysmotility and delayed transit as a cause of gastrointestinal symptoms in CF.

Impact of home parenteral nutrition on family members: A national multi-centre cross-sectional study.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a necessary treatment for patients with chronic, type 3, intestinal failure (IF). HPN often requires lifestyle adaptations, which are likely to affect quality of life (QoL) in both patients and family members. The aim of this study was to identify the level of burden on family members who are involved with HPN care and to understand specific factors that contribute to any burden. METHODS: Patients over the age of 18 and receiving HPN were identified in IF clinics from multiple centres across the U.K. Eligible patients were asked to complete the parenteral nutrition impact questionnaire (PNIQ) to assess their QoL, while family members were asked to complete the burden scale for family caregivers (BSFC). Logistical regression was undertaken giving adjusted odds ratios (aOR). RESULTS: 678 participants completed the survey representing 339 patients with their appointed family member. Mean PNIQ score was 11.53 (S.D. 5.5), representing a moderate impact of HPN on patients' QoL. On the BSFC scale, 23% of family members reported a moderate to very severe subjective burden indicating an increased risk of psychosomatic symptoms. After adjusting for age and gender, predictors of BSFC included: family members self-reported health status using the EuroQol visual analogue scale (aOR 19.91, 95% CI 1.69, 233.99, p = 0.017) and support received by health services (aOR = 5.83, 95% CI = 1.93, 17.56, p = 0.002). Employment status, disease type, number of nights on HPN and length of time on HPN were not associated with BSFC. CONCLUSIONS: Family members with a poor health status or lack of support by health service were more likely to have a moderate to very severe subjective burden. Tailored support from the multi-professional IF team may reduce the burden experienced by family members of people dependent on HPN.