The role of the microbiome in gastrointestinal inflammation.

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.

Clinical and Nutritional Care Pathways of Patients with Malignant Bowel Obstruction: A Retrospective Analysis in a Tertiary UK Center.

We describe a retrospective cohort study of patients with malignant bowel obstruction to examine their nutritional care pathways between 1.1.16 and 31.12.16 with readmissions until 31.12.17. Data were analyzed by comparing patients who were referred (R) and not referred (NR) for PN. We identified 72 patients with 117 MBO admissions (mean ± SD age:63.1 ± 13.1yrs, 79% female). 24/72 patients were in R group. Predominant primary malignancies were gynaecological and lower-gastrointestinal cancers (76%). 83% patients had metastases (61% sub-diaphragmatically). All patients were at high-risk of malnutrition and baseline mean weight loss was 7%. Discussion of PN at multidisciplinary team meeting (MDT) (22% vs.5%, P = 0.02) and dietetic contact (94% vs. 41%, P < 0.0001) were more likely to occur in the R group. In 13/69 MBO admissions in NR group, reasons for non-referral were unclear. Median baseline and follow-up weight was similar (55-55.8 kg). Overall survival was 4.7 (1.4-15.2)months, with no differences by referral groups. We compared a sub-sample of patients who 'may have' required PN (n = 10) vs. those discharged on home PN (n = 10) and found greater survival in the HPN group (323vs.91 day, P < 0.01). Our findings highlight disparity in care pathways suggesting that nutritional care should be integrated into clinical management discussion(s) at MDT to ensure equal access to nutritional services.

When is parenteral nutrition indicated in the hospitalized, acutely ill patient?

PURPOSE OF REVIEW: The current review discusses current practices regarding appropriate indications for parenteral nutrition in acutely ill hospitalized patients. We address-specific indications for parenteral nutrition in the perioperative period, and in inflammatory bowel disease, oncology, hepatobiliary, critical care and end-stage renal disease patients. RECENT FINDINGS: Acutely ill hospitalized patients can develop intestinal failure requiring parenteral nutrition. Recent studies have provided insight into the main indications. The most common indications for inpatient parenteral nutrition include postsurgical complications, including prolonged ileus, sepsis, fistula and leaks, and bowel obstruction, predominantly malignant. Severe or complicated inflammatory bowel disease and cancer treatment-related mucosal enteropathies (mucositis, enterocolitis, gut graft-versus-host disease) are the next commonest indications. Less frequent indications are primary motility disorders and inability to secure enteral access for enteral nutrition. Gastrointestinal failure of the intensive care patient is a separate entity resulting from multiple mechanisms, including an enteropathy and dysmotility. SUMMARY: Despite the wider availability of nutrition support teams, use of parenteral nutrition is not without risk. The risks and benefits of parenteral nutrition in the acute setting need to be carefully considered even when it is indicated.

UK Patients of Bangladeshi Descent with Crohn's Disease Respond Less Well to TNF Antagonists Than Caucasian Patients.

BACKGROUND: Patients with inflammatory bowel disease are currently managed with the assumption that trial data are applicable to all ethnic groups. Previous studies demonstrate differences in disease severity and phenotype of Asian patients with Crohn's disease (CD), including Bangladeshi Asians within the UK. No study has evaluated the impact of ethnicity on response to anti-TNFs. AIM: Our primary endpoint was a comparison of failure-free survival on first prescribed anti-TNF (anti-tumor necrosis factor) therapy in UK Bangladeshi and Caucasian patients with CD. Our secondary aims were to evaluate disease phenotype, indication for anti-TNF prescription, and duration from diagnosis until first anti-TNF prescribed between groups. METHODS: The records of consecutive outpatient appointments over a 12-month period were used to identify Caucasian and Bangladeshi patients prescribed an anti-TNF for CD. Information on patient demographics, ethnicity, disease phenotype, immunomodulator use, outcome from first biologic, duration of therapy, and reason for cessation was recorded. RESULTS: In total, 224 Caucasian and Bangladeshi patients were prescribed an anti-TNF for CD. Bangladeshi patients started an anti-TNF 4.3 years earlier after diagnosis than Caucasian patients (3.9 years vs. 8.2 years: p < 0.01). Bangladeshi patients experienced shorter failure-free survival than Caucasian patients (1.8 vs. 4.8 years p < 0.01). By 2 years, significantly more Bangladeshi patients had stopped anti-TNF due to loss of response (OR 6.35, p < 0.01). CONCLUSIONS: This is the first study to suggest that Bangladeshi patients resident in the UK with CD respond less well to treatment with TNF antagonists than Caucasian patients.

Mainstreaming of genomic medicine in gastroenterology, present and future: a nationwide survey of UK gastroenterology trainees.

OBJECTIVE: Genomics and personalised medicine are increasingly relevant for patients with gastroenterological conditions. We aim to capture the current state of genomics training in gastroenterology to review current understanding, clinical experience and long-term educational needs of UK trainees. DESIGN AND SETTING: A web-based nationwide survey of all UK gastroenterology specialty trainees was conducted in 2017. RESULTS: 100 trainees (14% of UK gastroenterology trainees) completed this survey. Only 9% and 16% of respondents believe that their local training programme adequately prepares them for the future clinical practice using genomic medicine and personalised medicine, respectively. Barriers identified include the need for greater trainee education (95%), inadequate clinical guidance to base interventions on the results of genomic testing (53%), concerns over misinterpretation by patients (43%) and overuse/misuse of testing by clinicians (34%).Survey respondents felt prepared to perform HFE genotyping (98%), assess TPMT status (97%) and interpret HLA subtyping for suspected coeliac disease (85%). However, only a minority felt prepared to perform the following investigations: polyposis screening (34%), hereditary pancreatitis screening (30%), testing for Lynch yndrome (33%) and KRAS testing for colorectal cancer (20%).Most respondents would support holding dedicated training days on genomic medicine (83%), formal training provisions for the mainstreaming of genomic testing (64%), an update to the UK gastroenterology specialty training curriculum and examinations (57%) and better-defined referral pathways for local genomic services (91%). CONCLUSION: Most gastroenterology trainees in this survey feel ill equipped to practise genomic and personalised medicine as consultants. We propose specific revisions to the UK gastroenterology specialty curriculum that addresses trainees needs.

Enteral Nutrition in Adult Crohn's Disease: Toward a Paradigm Shift.

Medical and surgical treatments for Crohn's disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn's disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn's disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed.

Can Quantab titrator sticks reliably predict urinary sodium?

BACKGROUND & AIMS: Urinary sodium concentration is a commonly used marker for extracellular fluid depletion which is often associated with dehydration. A point of care test for urinary sodium may reduce delays in clinical decision making by offering more timely guidance leading to improved salt and fluid management. We compared laboratory assessed urinary sodium with a potential point of care measure of urinary chloride in a variety of in- and outpatient specialities, to explore its use as an indicator of low urine sodium. METHODS: Urinary chloride concentrations were estimated using a Quantab titrator stick in samples from patients that had been sent for urinary sodium assays. We validated the results of this titrator stick with laboratory-assessed sodium concentrations by deriving correlation coefficients between these methods and using limits of agreement testing. We determined the optimal titrator stick cut-point for identifying low urinary sodium (urinary sodium <20 mmol/L) by maximising the product of the sensitivity and specificity. This level of urinary sodium was used to mirror the British Society of Gastroenterology guidance on short bowel patients Nightingale and Woodward, 2006. RESULTS: We obtained laboratory urinary sodium concentration and Quantab stick chloride measures on 127 samples. Twenty three percent had a urinary sodium below 20 mmol/L so were regarded as biochemically dehydrated. A threshold of <4.3 on the Quantab scale had a positive predictive value for low sodium of 56% (95%CI 40%-71%) and a negative predictive value of 94% (95%CI 87%-98%). CONCLUSIONS: These data suggest that the Quantab stick could be used as a point of care test to aid fluid and salt management decisions in an outpatient setting. Further work to explore the use of the titrator stick in specific patient populations at risk of salt and water depletion is justified.

Herbs and Inflammatory Bowel Disease.

Although herbal preparations are widely used by patients with inflammatory bowel disease (IBD), evidence for their efficacy is limited and they may not always be safe. Mainly small studies of varying quality have suggested that several herbal preparations could be of benefit in IBD, but larger better-designed trials are needed to establish their place in inducing and maintaining remission. Patients and health care workers need to be made more aware of the limitations and risks of using herbal products for IBD.