Gut Symptoms Research Articles

P415 Improving food-related quality of life in Inflammatory Bowel Disease with a novel web-based intervention: a randomised controlled feasibility trial

Abstract Background Food-related quality of life (FR-QoL) refers to the psychosocial aspects and pleasure derived from food, eating and drinking. Impaired FR-QoL is prevalent in inflammatory bowel disease (IBD) and is associated with reduced intakes of fibre and certain micronutrients. Patient and health professional focus groups identified the need for web-based support and education on food in IBD, which was subsequently developed through experience-based co-design. The aim of this study was to establish the feasibility of a randomised controlled trial (RCT) investigating the effectiveness of the web-based intervention compared to usual care on FR-QoL in people with newly diagnosed IBD. Methods A randomised controlled feasibility trial was conducted in adults with Crohn’s disease or ulcerative colitis diagnosed in the preceding, 12 months. Patients with active and inactive IBD experiencing impaired FR-QoL (≤90 scored on the validated FR-QoL-29 questionnaire) were recruited. Participants were delivered usual care by their IBD team and were also randomised to either access to the web-based intervention (containing information and patient and clinician videos on various IBD-specific food and nutrition considerations) or no access to the website for, 12 weeks. Questionnaires were completed at baseline and end of trial to assess FR-QoL (FR-QoL-29), health-related quality of life (UK IBDQ), IBD distress (IBD Distress Scale) and anxiety and depression (HADS). Google Analytics was used to investigate usage of the web-based intervention. Results In total, 50 participants (ITT population) were recruited (81 screened), 30 randomised to the web-based intervention and, 20 to usual care, with, 48 completing the trial (PP population). In the ITT analysis, a greater increase in FR-QoL was observed in the web-based intervention (+11.7 SD, 18.2) than usual care group (+1.4 SD, 20.4, P=0.057), whilst IBD distress reduced in the web-based intervention (-6.8 SD, 26.6) and increased in the usual care group (+8.3 SD, 25.5, P=0.052). Participants in the web-based intervention group logged into the website an average of, 4.2 (SD, 2.9) times, and spent an average of, 13 minutes, 41 seconds (SD, 15 minutes, 1 second) on the website per visit. The most frequently accessed content covered dietary management of specific gut symptoms (accessed by, 52% of participants). In qualitative interviews the participants reported the intervention to be clear, user friendly, easy to navigate, and a good source of educational information. Conclusion This feasibility study demonstrates that a RCT of a web-based intervention is feasible and potentially effective in improving FR-QoL in IBD. An adequately powered RCT investigating the effectiveness of this intervention in IBD is feasible and now warranted.

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D

ABSTRACT Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.

Gut Microbiome and Its Role in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction, and the microbiome has often been implicated as a central player in its pathophysiology. Patients with irritable bowel syndrome display altered composition and function of the gut microbiota compared to healthy controls. Microbiome directed therapies, such as probiotics, antibiotics and fecal microbiome transplantation, appear to be beneficial for both gut symptoms and psychiatric comorbidities. This review aims to recapitulate the available literature on the microbiome contribution to the pathophysiology and symptoms presentation of irritable bowel syndrome, as well as the current literature on microbiome-targeted treatments for this disease.

An In Vitro Approach to Studying the Microbial Community and Impact of Pre and Probiotics under Anorexia Nervosa Related Dietary Restrictions.

Individuals with anorexia nervosa (AN) often suffer psychological and gastrointestinal problems consistent with a dysregulated gut microbial community. Psychobiotics have been postulated to modify microbiota and improve mental well-being and gut symptoms, but there is currently a lack of evidence for such approaches in AN. The aim of this study was to use an in vitro colonic model to evaluate the impact of dietary restrictions associated with AN on the intestinal ecosystem and to assess the impact of pre and probiotic intervention. Bacteriology was quantified using flow cytometry combined with fluorescence in situ hybridisation and metabolic end products (including neurotransmitters) by gas chromatography and liquid chromatography mass spectrometry Consistent with previous research, the nutritional changes significantly reduced total microbiota and metabolites compared with healthy conditions. Pre and probiotic supplementation on restricted conditions enhanced the microbial community and modulated metabolic activity to resemble that of a healthy diet. The model system indicates that nutritional changes associated with AN can impact the microbial community, and that these changes can, at least in part, be restored through the use of pre and probiotic interventions.

GUT SYMPTOMS LINKED WITH COVID-19: A SYSTEMATIC REVIEW

The most prevalent symptoms at the onset of COVID-19 are fever, cough, fatigue, myalgia, and dyspnea (shortness of breath). Initially, it was thought that the virus only causes respiratory distress in patients until the viral RNA has been detected in the patient’s stool. Recently, several new studies have depicted that COVID-19 has impact on gut patients. We hypothesized that, there may have a link between gut symptoms and COVID-19. Therefore, the present study was reviewed to explore this study question; searches were conducted to identify the articles related to the association between gut symptoms and COVID-19, which were published between 2019 to 2020. Multiple searches were conducted in Google Scholar and ResearchGate using keywords. In this review, a total of 2639 cases of COVID-19 from 20 articles had been analyzed with special emphasize on gut symptoms. Among 20 studies, Diarrhea (highest 71.62% and lowest 2%) was the most prevalent symptoms, respectively, nausea (highest 17.1% and lowest 1%) & vomiting (highest 16.7% and lowest 1%), anorexia (highest 66.7% and lowest 17.9%), and abdominal pain (highest 8.8% and lowest 1.9%). Along with the main symptoms, we studied some commonly associated symptoms, such as, fever (highest 98.6% and lowest 55.6%) and coughing (highest 91.67% and lowest 35%) were heavily linked with COVID 19. Despite all the GI symptoms associated with COVID 19, there are currently no recommendations for a diagnostic approach in the presence of gastrointestinal symptoms associated with the corona virus, and there is no definitive knowledge of the role of COVID-19 in the gastrointestinal diseases. So, further studies are needed to identify the better relationship between gut symptoms and SARS-CoV-2 for suppressing the spread of COVID-19.

A multicentre pilot study assessing the outcomes of the gut symptoms in neurological disease management (GUSTO) tool

Rationale: Intolerance in enterally fed patients with neurological conditions is common and there are currently various approaches to management1. The Gut Symptoms in Neurological Disease Management Tool (GUSTO) was developed by a multi-disciplinary team (MDT). This pragmatic tool is being used to provide guidance on the management of enteral feeding intolerance in multicentre acute and community sites. As part of a larger service evaluation, this pilot aimed to assess the outcomes of the GUSTO tool in clinical practice.

Perceived acceptability of partial enteral nutrition (PEN) using oral nutritional supplement drinks in adolescent and adult Crohn's disease outpatients: A feasibility study.

Studies, mainly in Japanese cohorts, have shown that partial enteral nutrition (PEN) including oral nutritional supplement (ONS) drinks can prolong disease remission and increase drug effectiveness in Crohn's disease (CD). Acceptability is a key feasibility parameter to determine whether PEN is a viable treatment option in UK CD patients. We report the results of a single centre cross-sectional feasibility study carried out to investigate perceived acceptability of PEN using ONS drinks and whether ONS preference varies with sex, nutritional status or phenylthiocarbamide (PTC) sensitivity. Patients with a confirmed CD diagnosis were recruited using convenience sampling from an adult and adolescent gastroenterology outpatient clinic over 3 years. Blind taste testing of 5 polymeric ONS drinks were conducted using a validated 9-point hedonic rating scale followed by completion of an acceptability questionnaire based on the preferred ONS drink. A subset of patients took home the preferred ONS drink for a 7-day ONS study. 105 CD patients (55 males), aged 34.9 (±15.4) years were recruited and 28 patients completed the 7-day ONS study. Overall impression scores did not significantly vary with nutritional status, sex, BMI, handgrip strength (HGS), mid-upper arm circumference (MUAC) or PTC sensitivity. Ensure plus milkshake™ rated highest for overall impression (6.5, p=<0.0001) and all other organoleptic properties (p<0.0001). The main perceived benefits of using ONS drinks as PEN related to assurance of nutrient intake (89%), convenience (86%), and improvement of gut symptoms (85%). The main perceived barriers related to reduction in pleasure from eating and drinking (56%), struggling with drink storage (54%) having less energy and feeling more tired than if eating 3 solid meals daily (52%). 65% of patients would consider using ONS drinks as PEN as a maintenance treatment option. 81% of patients felt confident-very confident about consuming ONS drinks daily as PEN for three months but this dropped to 64% and 37% at 6 and 12 months, respectively. There was a significant drop in perceived ease of use of ONS drinks as PEN after the 7-day ONS study (P=0.01). Use of ONS drinks as PEN have high perceived benefits and appear to be a feasible option for short-term use of 3-6 months in CD patients. However, confidence in long-term use of ONS drinks as PEN is low mainly due to the perceived social impact. Future studies should assess longer trial periods and volume of ONS drinks to increase the validity of these findings.

Acute GvHD after HLA-Haploidentical Hematopoietic Cell Transplantation with Regulatory and Conventional T Cell Immunotherapy Does Not Adversely Affect Transplantation Outcomes

IntroductionAdoptive immunotherapy with CD4+CD25+FOXP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) has been employed after allogeneic hematopoietic stem cell transplantation (HSCT) to prevent Graft-versus-Host Disease (GvHD) while mantaining Graft-versus-Leukemia effect in the absence of any further immune suppressive GvHD prophylaxis (Di Ianni, Blood 2011; Martelli, Blood 2014). A recent study of age-adapted haploidentical HSCT with Treg/Tcon adoptive immunotherapy (Treg/Tcon haplo-HSCT) resulted in an unprecedented 75% chronic GvHD (cGvHD)/leukemia-free survival (CRFS) in acute myeloid leukemia patients. Acute GvHD (aGvHD) occured in 33% of patients and was the most frequent complication of the procedure (Pierini, Blood Advances 2021). Here, we analyzed clinical and histological characteristics of aGvHD and evaluated its impact on outcomes in patients who received Treg/Tcon haplo-HSCT.MethodsWe retrieved data of patients who underwent Treg/Tcon haplo-HSCT at Perugia University Hospital and who were evaluable for aGvHD from January 2015 until June 2021 (clinicaltrials.gov: NCT03977103). Histological features and lymphoid infiltration by immunohistochemistry were analyzed in gut samples of patients who received diagnostic colonscopy and biopsy for gastrointestinal symptoms.ResultsA total of 105 patients engrafted after Treg/Tcon haplo-HSCT. Mean age at transplant was 48 years (range 18-70). Acute leukemia was the most frequent diagnosis (78/105 myeloid, 23/105 lymphoblastic), 4 patients had myelodisplastic syndrome and 2 multiple myeloma. Twenty-seven (26%) patients had active disease at the time of HSCT. Fourteen (13%) patients received Treg/Tcon haplo-HSCT as a second HSCT procedure. Thirty-one (29%) patients developed grade II-IV aGvHD. Four patients had grade II aGvHD, 23 grade III, and 4 grade IV. Almost all patients (90%) presented gut involvement, while skin was involved in 64% of them and liver in 35%. To explain why gut symptoms such as diarrhea and abdominal pain were more frequently present than symptoms of skin or liver involvement, we evaluated 40 histological samples from 34 patients who received colonoscopy for suspected aGvHD. Twenty-two of them (65%) received a clinical diagnosis of aGvHD and pharmacological immune suppression was promptly started. Clinical diagnosis did not always match histological findings: biopsies were suggestive of aGvHD in 20/22 patients who required treatment, but also in 8/12 patients who did not. We found no difference in median CD3+ cell infiltration among patients who did not need immune suppressive treatments and patients with aGvHD (460 cells/mmq vs 446 cells/mmq). However, FOXP3+ Tregs preferentially infiltrated gut mucosa of patients who resolved clinical symptoms with no need of immune suppressive treatments (120 cells/mmq vs 59 cells/mmq, p = 0.008; FOXP3/CD3 ratio: 0.27 vs 0.18, p = 0.004). This observation suggested Treg defective homing to gut mucosa of aGvHD patients. Indeed, we found infused Tregs expressed lower levels of gut homing receptor α4β7 in comparison with Tcons (p< .001).Despite severe presentation at diagnosis, aGvHD resolved in the majority of patients (71%), and immune suppressive therapy could be completely withdrawn after a relatively short-course (median: 98 days, range 48-404). Sixteen/31 patients (52%) were steroid refractory and required further treatments after first-line (e.g. Ruxolitinib). Only two of them developed moderate/severe cGvHD and one is alive and off-therapy.Indeed, aGvHD diagnosis did not result in higher incidence of non-relapse mortality (cumulative incidence of 29% in aGvHD patients vs 27% in controls; p=non significant, ns, Fig.1A), relapse (13% vs 20%; p=ns, Fig.1B), or cGvHD (6.5% vs 3%; p=ns, Fig.1C). In fact, CRFS of aGvHD patients was similar to CRFS of patients that did not develop aGvHD (Fig. 1D, p=ns, median follow up of live patients: 1246 days).ConclusionsTreg/Tcon haplo-HSCT is followed by low rates of relapse and cGvHD and results in good CRFS in high risk leukemia patients. aGvHD after Treg/Tcon haplo-HSCT preferentially involves the gut where Treg homing is defective. Strategies that enhance Treg homing in the gut (e.g. low-dose IL-2) may help reduce aGvHD after Treg/Tcon haplo-HSCT. In conclusion, despite aGvHD occurred in 29% of patients, it was responsive to treatments and it did not result in disease relapse or cGvHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P34 The value of combined ophthalmology and rheumatology review- an unmet need

Case report - IntroductionRheumatic diseases manifest in different specialties including ophthalmology. Presentation with eye symptoms may be a sight-threatening emergency such as GCA. Other inflammatory symptoms such as uveitis present to the Eye Casualty frequently, which need prompt rheumatologist input for a holistic management.Case report - Case descriptionWe present an interesting case with multiple learning points for both rheumatologists as well as ophthalmologists.We present a case of a 73-year-old Caucasian lady who initially presented to the Eye Department. She was diagnosed as having bilateral uveitis by the ophthalmologist with an interest in uveitis. She had various investigations which showed positive HLA-B27 status, ENA, ANA, serum ACE level were normal; however, she was found to have raised immunoglobulins and plasma viscosity. She was treated with steroid eye drops and intravitreal dexamethasone implant in both eyes. She is a steroid responder and unfortunately developed glaucoma which needed two surgical procedures. She developed chronic cystoid macular oedema in Left eye.She did not have any symptoms of psoriasis or gut symptoms suggestive of inflammatory bowel disease. She did report symptoms of inflammatory bowel disease. She had an MRI of axial spine as per AS protocol, which confirmed inflammatory spondyloarthropathy. She was diagnosed to have non-radiographic spondyloarthropathy which is managed by simple anti-inflammatories. Her BASDAI is less than 3 and does not qualify for biologic treatment for her axial spondyloarthropathy. Her main symptoms were ocular, which is very active and she is not able to escalate to biologic therapy.Case report - DiscussionThis is a patient presenting with late-onset inflammatory back pain without any articular or extra-articular activity. Her main manifestation is spectrum of spondyloarthropathy with uveitis; however, we could not escalate her to biologics. She has been on topical, intraocular and oral steroids which has led on to complications. The combined clinic between rheumatologists and ophthalmologists is key in managing such patients.Case report - Key learning pointsRecurrent uveitis in HLA-B27 patients needs to be reviewed in ophthalmology combined services with rheumatologists to establish the diagnosis of SpADelay of diagnosis of SpA can be reduced by establishing combined uveitis/SpA services within the NHS widely

NLRC4 GOF Mutations, a Challenging Diagnosis from Neonatal Age to Adulthood.

The NLRC4 inflammasome is part of the human immune innate system. Its activation leads to the cleavage of pro-inflammatory cytokines IL-1β and IL-18, promoting inflammation. NLRC4 gain-of-function (GOF) mutations have been associated with early-onset recurrent fever, recurrent macrophagic activation syndrome and enterocolitis. Herein, we describe two new patients with NLRC4 mutations. The first case presented with recurrent fever and vasoplegic syndrome, gut symptoms and urticarial rashes initially misdiagnosed as a severe protein-induced enterocolitis syndrome. The second case had recurrent macrophage activation syndrome (MAS) and shock, suggesting severe infection. We identified two NLRC4 mutations, on exon 4, within the nucleotide-binding protein domain (NBD). After a systematic review of NLRC4 GOF mutations, we highlight the wide spectrum of this disease with a limited genotype–phenotype correlation. Vasoplegic shock was only reported in patients with mutation in the NBD. Diagnosing this new entity combined with gastrointestinal symptoms and vasoplegic shocks is challenging. It mimics severe allergic reaction or sepsis. The plasma IL-18 level and genetic screening are instrumental to make a final diagnosis.

Hot Topics in Recent Parkinson's Disease Research: Where We are and Where We Should Go.

Parkinson's disease (PD), the second most common neurodegenerative disease, is clinically characterized by both motor and non-motor symptoms. Although overall great achievements have been made in elucidating the etiology and pathogenesis of PD, the exact mechanisms of this complicated systemic disease are still far from being clearly understood. Consequently, most of the currently-used diagnostic tools and therapeutic options for PD are symptomatic. In this perspective review, we highlight the hot topics in recent PD research for both clinicians and researchers. Some of these hot topics, such as sleep disorders and gut symptoms, have been neglected but are currently emphasized due to their close association with PD. Following these research directions in future PD research may help understand the nature of the disease and facilitate the discovery of new strategies for the diagnosis and therapy of PD.

Nutrient, Fibre, and FODMAP Intakes and Food-related Quality of Life in Patients with Inflammatory Bowel Disease, and Their Relationship with Gastrointestinal Symptoms of Differing Aetiologies.

Background and AimsCertain foods are reported as gut symptom triggers in inflammatory bowel disease [IBD], and fructans are shown to worsen non-inflammatory symptoms in inactive IBD, which may result in self-imposed dietary restrictions. The aim of this study was to investigate nutrient and FODMAP intakes, and the relationship between gut symptoms and dietary intake, in IBD.MethodsNutrient, fibre, and FODMAP intakes were estimated using 7-day food records in patients with active IBD [Active IBD], inactive IBD with non-inflammatory gut symptoms [Inactive IBD-GI], inactive IBD without gut symptoms [Inactive IBD], and healthy controls. Nutrient intakes, numbers of participants achieving national recommendations, and food-related quality of life [FR-QoL] were compared across study groups.ResultsFood diaries were obtained from 232 patients with IBD [65 Active IBD, 86 Inactive IBD-GI, 81 Inactive IBD] and 84 healthy controls. Patients with Active IBD had significantly lower intakes of numerous micronutrients, including iron, folate, and vitamin C, compared with controls. All IBD groups consumed less total fibre [4.5 to 5.8 g/day] than controls [p = 0.001], and total FODMAP and fructan intakes were lower in Active IBD compared with controls. Strikingly, FR-QoL was significantly lower in all IBD groups compared with controls [all p = 0.001].ConclusionsThis study revealed lower intakes of fibre, FODMAPs, and micronutrients, in addition to poorer FR-QoL, in Active IBD and Inactive IBD-GI with gut symptoms compared with healthy controls. Future research should address dietary restrictions responsible for these differences.

Fecal Short-Chain Fatty Acid Ratios as Related to Gastrointestinal and Depressive Symptoms in Young Adults.

Short-chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders, and recent data indicate relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut symptoms in young adults. Fecal samples from 164 individuals (125 were patients with psychiatric disorders: mean [standard deviation] age = 21.9 [2.6] years, 14% men; 39 nonpsychiatric controls: age = 28.5 [9.5] years, 38% men) were analyzed for the SCFA acetate, butyrate, and propionate by nuclear magnetic resonance spectroscopy. We then compared SCFA ratios with dimensional measures of self-reported depressive and gut symptoms. Depressive symptoms showed a positive association with acetate levels (ρ = 0.235, p = .003) and negative associations with both butyrate (ρ = -0.195, p = .014) and propionate levels (ρ = -0.201, p = .009) in relation to total SCFA levels. Furthermore, symptoms of diarrhea showed positive associations with acetate (ρ = 0.217, p = .010) and negative associations with propionate in relation to total SCFA levels (ρ = 0.229, p = 0-007). Cluster analysis revealed a heterogeneous pattern where shifts in SCFA ratios were observed in individuals with elevated levels of depressive symptoms, elevated levels of gut symptoms, or both. Shifts in SCFAs are associated with both depressive symptoms and gut symptoms in young adults and may have of relevance for treatment.

P168 Depression and fatigue dependent variation of gut microbiome in patients with active Inflammatory Bowel Disease

Abstract Background Fatigue and depression are highly prevalent extraintestinal symptoms in IBD, especially during active disease. The underlying mechanisms are still poorly understood, but an involvement of the microbiota-gut-brain-axis seems likely. The aim of this study was to examine associations between the gut microbiota and symptoms of fatigue and depression in patients with active IBD. Methods We included 62 patients with active IBD. Blood and stool samples were collected before a change of therapy and patients completed questionnaires regarding fatigue (WEIMuS) and depression (HADS). Fecal microbiota were analyzed by means of shotgun metagenomic sequencing. Based on taxonomical and functional metagenomic annotations of gut microbiome, we investigated the correlation between functional modules and psychometric scores as well as the nature of co-occurrence networks on the genus level using Bayesian statistical methods and analyzed modulating effects of fatigue and depression on genera co-occurrence. CRP levels as well as age, gender, diagnosis and medication were included as nuisance variables. Results Half of the patients (n=31) were fatigued (WEIMuS &amp;gt;/= 32P.), and 18 patients reported symptoms of at least mild to moderate depression (HADS D &amp;gt;/=10P.). Co-occurrence of genera that is influenced by depression or fatigue in this active IBD-sample with is displayed in Figure 1 (Log10(BF10) ≥ 1.0, strong evidence for H1). Evidence for an influence of depression severity was found for 10 genera combinations, with the strongest effects on the Dorea-Butyrococcus-association (Log10(BF10) = 1.41, increase of association strength with higher depression score) and the association between an unknown genus of the Coriobacteriaceae family with Arabia (Log10(BF10) = 1.00, decrease of association strength with higher depression score). Modulatory effects of fatigue severity was present in 10 genera combinations, most pronounced for the Azospirillum-Akkermansia- (Log10(BF10) =2.39, increase of association strength with higher fatigue-score) and Odoribacter-Actinomyces-association (Log10(BF10) =1.58, decrease of association strength with higher fatigue-score) (Figure 2). Conclusion This study is the first to address the relationship between extraintestinal symptoms like fatigue and depression and microbiota parameters in patients with active IBD by means of network analysis with Bayesian methods. Our results show strong associations between these symptoms and co-occurring genera in a sample-specific network, indicating a role of the microbiota-gut-brain-axis in the development of fatigue and depression during active disease.

Dietary Intake and Gastrointestinal Integrity in Runners Undertaking High-Intensity Exercise in the Heat.

Gastrointestinal disturbances are one of the most common issues for endurance athletes during training and competition in the heat. The relationship between typical dietary intake or nutritional interventions and perturbations in or maintenance of gut integrity is unclear. Twelve well-trained male endurance athletes (peak oxygen consumption = 61.4 ± 7.0ml·kg-1·min-1) completed two trials in a randomized order in 35 °C (heat) and 21 °C (thermoneutral) conditions and kept a detailed nutritional diary for eight consecutive days between the two trials. The treadmill running trials consisted of 15min at 60% peak oxygen consumption, 15min at 75% peak oxygen consumption, followed by 8 × 1-min high-intensity efforts. Venous blood samples were taken at the baseline, at the end of each of the three exercise stages, and 1hr postexercise to measure gut integrity and the permeability biomarker concentration for intestinal fatty-acid-binding protein, lipopolysaccharide, and lipopolysaccharide-binding protein. The runners self-reported gut symptoms 1hr postexercise and 3days postexercise. The heat condition induced large (45-370%) increases in intestinal fatty-acid-binding protein, lipopolysaccharide-binding protein, and lipopolysaccharide concentrations compared with the baseline, but induced mild gastrointestinal symptoms. Carbohydrate and polyunsaturated fat intake 24hr preexercise were associated with less lipopolysaccharide translocation. Protein, carbohydrate, total fat, and polyunsaturated fat intake (8 days) were positively associated with the percentage increase of intestinal fatty-acid-binding protein in both conditions (range of correlations, 95% confidence interval = .62-.93 [.02, .98]). Typical nutrition intake partly explained increases in biomarkers and the attenuation of symptoms induced by moderate- and high-intensity exercise under both heat and thermoneutral conditions.

Long-term symptom severity in people with irritable bowel syndrome following dietetic treatment in primary care: A service evaluation.

Evidence suggests that dietary interventions can improve symptoms in people with irritable bowel syndrome (IBS), although most data explore the short-term (immediate) impact. Data on long-term (>6months) impact are limited, especially from primary care settings. The present study aimed to investigate the long-term effect of dietetic-led interventions for IBS delivered in primary care. A service evaluation of a dietetic-led IBS clinic was completed, analysing data on symptom severity, stool frequency and consistency, and healthcare input. Data were collected before and immediately after dietary intervention as part of patients' routine clinical appointments. Long-term data were collected via a postal questionnaire at least 11months later. In total, 211 patients responded to the long-term follow-up questionnaire at a median of 13months (interquartile range 12-16months) post follow-up appointment. Of these, 84% had been advised to follow a low FODMAP (i.e., fermentable oligosaccharides, disaccharides, monosaccharides and polyols carbohydrates) diet. All symptoms were reported significantly less frequently short term, and all except heartburn and acid regurgitation remained so over the long term. The four most commonly reported bowel symptoms reduced in frequency were abdominal pain (62%), bloating (50%), increased wind (48%) and urgency to open bowels (49%) (p<0.001). The percentage of patients reporting satisfactory relief of gut symptoms was 10% at baseline and 55% at long-term follow-up (p<0.001). Visits to a general practitioner were reduced (from 96% to 34%; p<0.001), as were those to the gastroenterologist (from 37% to 12%; p=0.002), during the year prior to long-term follow-up compared to the year prior to dietary intervention. Patients with IBS who received dietetic-led interventions in primary care reported long-term symptoms improvements that may result in reduced healthcare usage.

A8 DIETARY TRYPTOPHAN MODULATES KYNURENINE AND INDOLE PRODUCTION IN HEALTHY INDIVIDUALS

Abstract Background Tryptophan is an essential amino acid that is transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity, mood and circadian rhythms. In particular, indoles, produced by gut bacterial metabolism of tryptophan, have recently gained central attention. Indoles are activators of the aryl hydrocarbon receptor (AhR), which is crucial for the maintenance of intestinal homeostasis and immunity. Tryptophan supplementation in fortified foods have been advocated to prevent chronic inflammatory conditions, from autism to chronic inflammation. However, whether dietary tryptophan supplementation affects immune function, tryptophan metabolic pathways and gastrointestinal symptoms in healthy subjects, is unknown. Aims To assess whether tryptophan supplementation, in healthy subjects on a low tryptophan diet, induces changes in microbiota-derived metabolites (indoles), host cytokine production or gut symptoms. Methods We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy individuals, between 18 and 75 years old, following a regular diet. Subjects were instructed to start a standardized low tryptophan diet and were randomly assigned to a 3-week tryptophan supplement (3gr/day) or placebo. After a 2-week washout period, subjects were crossed over to the opposite 3-week intervention arm. Self-administered questionnaires (GSRS, DASS21 and HADS) were used to assess gastrointestinal symptoms and mood/anxiety/stress. Stool, urine and blood samples were collected to measure tryptophan metabolites (kynurenine pathway and indoles) and cytokines. Results Supplementation of tryptophan was well tolerated and no changes in gastrointestinal symptoms or mood/anxiety were found. Compared with placebo, tryptophan supplementation increased urinary and plasma levels of indoleamine 2,3-dioxygenase (p= 0.002 and p= 0.02, respectively), a key enzyme in the kynurenine pathway, and of several indoles (p= 0.0008 and p= 0.01, respectively), suggestive of activation of microbial and host metabolic pathways. However, there were no measurable changes in the host cytokine production. There was a positive correlation between fecal kynurenine levels and anxiety and depression scores, suggesting that microbial metabolites may impact host behavior in humans. Conclusions Dietary tryptophan supplementation in healthy individuals was safe and had a measurable effect on microbial and host metabolism, mainly kynurenine and indole pathways, with known immunomodulatory properties. Although no effects on cytokine production were found, further studies are warranted to investigate tryptophan supplementation in disorders with altered AhR pathway, such as inflammatory bowel disease, metabolic syndrome and celiac disease. Funding Agencies None

Effects of high-carbohydrate versus mixed-macronutrient meals on female soccer physiology and performance

Athletes are often told to minimize intakes of fiber, fat, and protein in pre-competition meals to avoid gut distress, but this guidance is based on scant direct evidence. This study evaluated the physiological and perceptual effects of pre-competition mixed-macronutrient (MM) and high-carbohydrate (HCHO) meals in collegiate female soccer players. Fifteen players participated in this randomized, investigator-blinded, crossover study involving two ~ 1000-kcal meals (HCHO and MM) consumed 4h prior to 70-min scrimmages. Assessments included global positioning system (GPS) tracking, heart rate (HR), perceived exertion (RPE), ratings of fatigue (ROF), gut symptoms, and perceptions of satiety, hunger, and fullness. Differences between conditions for HR, RPE, ROF, and gut symptoms were evaluated with Wilcoxon signed-rank tests. GPS data and hunger, satiety, and fullness scores were compared using within-subjects repeated measures ANOVAs. No statistically significant differences were found between the conditions at any time point for HR, RPE, ROF, or gut symptoms. Significant time effects were found for two GPS variables (total distance covered and high-speed running), indicating that participants covered less distance during the second half of the scrimmages in comparison to the first half. However, there were no significant condition or condition × time interactions for GPS data. Finally, there were no condition or condition × time interactions for hunger, fullness, and satiety, though significant time effects were observed. A MM meal consumed 4h prior to 70min of soccer competition does not increase gut symptoms and can be similarly ergogenic as a HCHO meal.

Gut in COVID 19-is it worth noticing.

Although much has been talked and written about the respiratory menace that Coronavirus disease causes, a close examination reveals that gut symptoms are equally important diagnostic markers for COVID-19. Almost 53% of COVID-19 patients experience gastrointestinal (GI) symptoms. The entry of the SARS Cov-2 virus is mediated through angiotensin-converting enzyme receptors which are abundant in the GI tract. The virus also affects the GI tract through the gut lung axis. In addition to the GI tract epithelium, hepatobiliary and pancreatic systems are also affected in COVID through multiple mechanisms. GI manifestations vary from relatively benign symptoms such as nausea vomiting diarrhea to rare cases of life-threatening mesenteric vein thrombosis. The relationship of the symptoms with morbidity and mortality is not clear. Anorexia is related to inflammation, and agneusia and anosmia carry a good prognosis. Psychiatric manifestations may be more common in those with GI affection, inflammation being the common pathogenic factor. Treatment is symptomatic, and proper hygiene precautions are necessary considering the possible fecal shedding of the virus, especially during endoscopic procedures on the GI tract.

Gut Microbiome and Nonalcoholic Fatty Liver Disease (NAFLD): Implications for Nursing Care of Individuals Living With Chronic Metabolic Diseases.

At present, the incidence of nonalcoholic fatty liver disease (NAFLD) in adults is increasing year by year and at a younger age. Evidence-based healthcare has confirmed that NAFLD is closely related to obesity, cardiovascular disease, type 2 diabetes, metabolic syndrome, and other chronic metabolic diseases. Despite the growing prevalence of NAFLD, little is known about symptoms for patients at risk of NAFLD progression, thus preventing healthcare providers from intervening at an early stage. In addition, these symptoms usually cause problems for patients to cope with other chronic metabolic diseases. Symptoms may have a biological basis; especially as the changes of gut microbes may affect the symptoms of metabolic diseases. This article aims to describe the new role of gut microbes in the development of NAFLD, focusing on the potential relationship between gut microbes and symptoms of NAFLD, as well as the mechanism of action of the "gut-liver-brain" axis. This information can be useful in developing precise nursing interventions for NAFLD patients, restoring the "health" of gut microbes, and alleviating the symptom burden of chronic metabolic disease in NAFLD.