Fecal-adherent mucus is a non-invasive source of primary human MUC2 for structural and functional characterization in health and disease.

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1-2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.

User testing to modify the MyHealthyGut digital health application for inflammatory bowel disease.

Introduction: Inflammatory bowel disease, characterized by chronic intestinal inflammation, can be subcategorized into Crohn's disease and ulcerative colitis. The treatment for these conditions is unique to each patient and may include lifestyle changes, pharmaceutical intervention, and surgery. Lifestyle changes, such as dietary intervention, are a cornerstone of inflammatory bowel disease symptom management. Given the daily burden of this disease, self-management is paramount in coping with and/or minimizing symptoms. The MyHealthyGut application, successfully proven to be a self-management tool for celiac disease, shows promise for use in an inflammatory bowel disease patient population. Objective: To conduct user testing to gather valuable insights for the development of an IBD-focused version of the existing MyHealthyGut app. Methods: Participants included inflammatory bowel disease patients and healthcare practitioners. Participants used the application for a 2-week period, followed by participation in a focus group or individual interview to provide feedback. Qualitative questionnaires were administered verbally and feedback was recorded. Thematic analysis techniques were used for data quantification and analysis. Results: 15 participants were recruited and enrolled. Of these, 14 participants took part in the focus group and/or individual interviews. The feedback suggested changes related to clinical uses, food and symptom tracking, ease of use, and educational content. All (100%) participants reported that they would either use the application themselves or recommend it to patients, once their suggestions were implemented. Conclusion: Through user testing and feedback collection, priorities for app modification were identified. Areas for modification in the app functions and features, ease of use, and content were identified. Once updated to meet the needs of inflammatory bowel disease patients, the MyHealthyGut app may be a useful tool for IBD self-management.

Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis.

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: -1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).

A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial.

BACKGROUND AND AIMS: Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC. METHODS: We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing. RESULTS: The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 µg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii]. CONCLUSIONS: An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.

To Fiber or Not to Fiber: The Swinging Pendulum of Fiber Supplementation in Patients with Inflammatory Bowel Disease.

Evidence-based dietary guidance around dietary fiber in inflammatory bowel disease (IBD) has been limited owing to insufficient reproducibility in intervention trials. However, the pendulum has swung because of our increased understanding of the importance of fibers in maintaining a health-associated microbiome. Preliminary evidence suggests that dietary fiber can alter the gut microbiome, improve IBD symptoms, balance inflammation, and enhance health-related quality of life. Therefore, it is now more vital than ever to examine how fiber could be used as a therapeutic strategy to manage and prevent disease relapse. At present, there is limited knowledge about which fibers are optimal and in what form and quantity they should be consumed to benefit patients with IBD. Additionally, individual microbiomes play a strong role in determining the outcomes and necessitate a more personalized nutritional approach to implementing dietary changes, as dietary fiber may not be as benign as once thought in a dysbiotic microbiome. This review describes dietary fibers and their mechanism of action within the microbiome, details novel fiber sources, including resistant starches and polyphenols, and concludes with potential future directions in fiber research, including the move toward precision nutrition.

The effects of fasting diets on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. There is no confirmed treatment for NAFLD as yet. Recently, fasting regimens and their relationship to NAFLD have drawn a great deal of attention in the literature. We review the current evidence that supports fasting diets as an adjunctive therapeutic strategy for patients with NAFLD and address potential action mechanisms. We reason that the fasting diets might be a promising approach for modulating hepatic steatosis, fibroblast growth factors 19 and 21 signaling, lipophagy, and the metabolic profile.

A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model.

There is a growing appreciation that the interaction between diet, the gut microbiota and the immune system contribute to the development and progression of inflammatory bowel disease (IBD). A mounting body of scientific evidence suggests that high-fat diets exacerbate IBD; however, there is a lack of information on how specific types of fat impact colitis. The Mediterranean diet (MD) is considered a health-promoting diet containing approximately 40% total fat. It is not known if the blend of fats found in the MD contributes to its beneficial protective effects.Mice deficient in the mucin 2 gene (Muc 2-/-) were weaned to 40% fat, isocaloric, isonitrogenous diets. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to diets composed of corn oil (CO, n-6 polyunsaturated-rich), olive oil (monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2-/- mice. The MD resulted in lower clinical and histopathological scores and induced tolerogenic CD103+ CD11b+ dendritic, Th22 and IL-17+ IL-22+ cells necessary for intestinal barrier repair. The MD was associated with beneficial microbes and associated with higher cecal acetic acid levels negatively correlated with colitogenic microbes like Akkermansia muciniphila. In contrast, CO showed a higher prevalence of mucin-degraders including A. muciniphila and Enterobacteriaceae, which have been associated with colitis.A dietary blend of fats mimicking the MD, reduces disease activity, inflammation-related biomarkers and improves metabolic parameters in the Muc2-/- mouse model. Our findings suggest that the MD fat blend could be incorporated into a maintenance diet for colitis.

Dietary fats modulate neuroinflammation in mucin 2 knock out mice model of spontaneous colitis.

Specific diets regulate neuroimmune responses and modify risk of inflammatory bowel diseases, including ulcerative colitis. A link between gut and brain inflammation is also emerging. We hypothesized that adjusting dietary fatty acid composition modulates the neuroimmune responses in the mucin 2 knock out mice model of spontaneous colitis. Mice were randomly divided into three groups and fed isocaloric diets that only differed in their fatty acid composition. Diets enriched with anhydrous milk fat, corn oil, or Mediterranean diet fats were used. After nine weeks, brain and serum concentrations of ten inflammatory cytokines were measured. Three of these cytokines, including interleukin (IL)-2, IL-12 p70 and interferon-γ, were differentially expressed in the brains of animals from the three diet groups while there were no differences in the serum concentrations of these cytokines. Since only limited information is available about the functions of IL-2 in the central nervous system, in vitro experiments were performed to assess its effects on microglia. IL-2 had no effect on the secretion of neurotoxins and nitric oxide by microglia-like cells, but it selectively regulated phagocytic activity and reactive oxygen species production by stimulated microglia-like cells. Modulation of microglial reactive oxygen species through altered brain IL-2 concentrations could be one of the mechanisms linking diets with modified risk of neuroimmune disorders including Parkinson's disease.

Dietary adherence to the Mediterranean diet pattern in a randomized clinical trial of patients with quiescent ulcerative colitis.

Background: The Mediterranean diet pattern (MDP) is believed to improve health and promote balanced inflammation and metabolism. While unknown, compelling evidence suggests that MDP could benefit patients with inflammatory bowel disease (IBD). We aimed to evaluate the level of diet adherence, diet quality, and nutritional adequacy of the MDP in patients with Ulcerative Colitis (UC). Methods: Adult participants (n = 32) with quiescent UC were randomized to follow a MDP (n = 18) or Canadian Habitual Diet (CHD) (n = 14) for 12 weeks. The MDP participants received tailored nutrition education from a Registered Dietitian. Demographic, clinical data, medical history, and quality of life were assessed with the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), dietary adherence with the Mediterranean Diet Serving Score (MDSS), diet quality via the Healthy Eating Index-2015 (HEI-2015), and dietary intake (ASA-24) were completed at baseline and week 12. Results: Participants' diets were analyzed (MDP n = 15, CHD n = 13). The MDP (n = 10, 67%) achieved a high level of adherence (MDSS score between 16 and 24) vs. CHD (n = 3), (p = 0.030). HEI-2015 significantly increased from baseline to week 12 (p = 0.007) in the MDP and was significantly higher at week 12 compared to the CHD (p = 0.0001). The SIBDQ (bowel domain) showed reductions in the passage of large amounts of gas (p = 0.01) and improvements in tenesmus (p = 0.03) in the MDP. Despite enhanced diet quality and adherence in the MDP, females had inadequate intakes of calcium, iron, vitamin D, vitamin E, and choline and males had inadequate intakes of fiber, vitamin D, vitamin E, and choline. No adverse events were reported. Conclusion: With nutrition education, high adherence to the MDP was achieved without an increase in bowel symptoms. Following the MDP led to a higher diet quality; however, nutritional inadequacies were identified. Tailored dietary education focusing on nutrients of concern when following the MDP is recommended to ensure nutritional adequacy. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT03053713].

Deletion of mucin 2 induces colitis with concomitant metabolic abnormalities in mice.

Patients with inflammatory bowel disease (IBD) are at increased risk of under-recognized metabolic comorbidities. Chronic intestinal inflammation in IBD along with changes to the gut microbiome leads to broader systemic effects. Despite the existence of multiple animal models to study colitis, limited studies have examined the metabolic abnormalities associated with these models. In this study, a spontaneous model of colitis (mucin 2 knock-out mouse, Muc2-/-) was used to investigate the impact of intestinal disease on metabolic dysfunction. Before the onset of severe colitis, such as rectal prolapse, Muc2-/- mice exhibited impaired glucose clearance. Defects were noted in the insulin signaling pathway corresponding with upregulated genes in lipid utilization pathways, increased mitochondrial number, and peroxisome proliferator-activated coactivator 1α (PGC-1α), a transcription factor central to energy metabolism regulation. Parallel to these metabolic alterations, Muc2-/- mice exhibited systemic inflammation and bacteremia. We further characterized the dysbiotic microbiome's predicted functional categories given its contributing role to the colitic phenotype in the Muc2-/- mice. In addition to less butyrate levels, we show an increased predisposition to lipid metabolism and lipid biosynthesis pathways in the microbiome associated with the host's altered metabolic state. This study establishes the Muc2-/- mouse model that develops spontaneous colitis, as an ideal model for studying early comorbid metabolic dysfunction. Clarification of the underlying etiology of two phenotypes in this model could unravel important clues regarding the treatment of metabolic comorbidities during colitis.NEW & NOTEWORTHY This study discloses the impaired systemic energy metabolism in a classic colitis murine model (Muc2-/- knock-out model). Investigating the interaction between colitis and metabolic disorders helps to extend our knowledge on deciphering inflammatory bowel disease-associated comorbidities and provides new insight into clinical treatment.

Fish oil supplementation reduces maternal defensive inflammation and predicts a gut bacteriome with reduced immune priming capacity in infants.

Habitual supplementation of fish oil is thought to provide benefits to the developing infant; however, the effects on infant microbial establishment and immune development are unknown. A 6-month observational cohort study was conducted where 47 out of 91 women self-administered dietary fish oil during breastfeeding. Infant stool and mothers' breast milk were collected each month over 6 months. Gas chromatography was used to quantify breast milk fatty acids and high-throughput sequencing was used to assess the infant fecal microbiota. Immune markers and parent-reported questionnaires were used to assess infant immunity and health up to 2 years. Our results reveal that fish oil supplementation decreased secretory immunoglobulin A and increased IL-10 production in lactating women along with increased breast milk eicosapentaenoic acid, and this corresponded to increased abundances of fecal Bifidobacterium and Lactobacillus spp. in their infants. Docosahexaenoic acid levels in breast milk aligned with decreases in infant gut bacterial richness and the predicted bacterial phenotypes suggested that fish oil lowers commensal traits involved in pathogen colonization resistance. Despite this, there were no differences in sickness incidence in toddlers. This study revealed that fish oil associates with decreases in breast milk defensive inflammatory responses and corresponds with infant fecal microbiota with anti-inflammatory potential.

Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance.

We performed a scoping review on sought-after complementary therapies for patients with inflammatory bowel disease (IBD), specifically diet, physical activity and exercise (PA/E), and psychotherapy. We aim to update patients with IBD on therapies for self-care and provide physicians with guidance on how to direct their patients for the management of IBD. A search of MEDLINE, EMBASE, and PUBMED was completed in Sept 2016. Studies on diet, PA/E, or psychotherapy in patients with IBD were included. Medical Subject Heading terms and Boolean operators were used. The search was limited to full-text English articles describing an adult population. This review included 67 studies: Diet (n = 19); PA/E (n = 19); and psychotherapy (n = 29). We have made the following recommendations: (1) Diet: Consumption of diets rich in vegetables, fruit and soluble fiber may be beneficial in IBD. A trial of a low FODMAP diet can be considered in those patients with functional gastrointestinal symptoms. Restrictive diets are lacking in evidence and should be avoided; (2) PA/E: Regular low-moderate intensity activity, including cardiovascular and resistance exercise, has been shown to improve quality of life (QOL) and may improve inflammation; and (3) psychotherapy: Therapies such as cognitive-behavioural interventions, mindfulness, hypnosis, and stress management have been shown to improve QOL, but evidence is limited on their impact on anxiety, depression, and disease activity. Overall, these complementary therapies are promising and should be used to treat patients with IBD from a more holistic perspective.

Development of a screening tool to detect nutrition risk in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Malnutrition is a known complication of Inflammatory Bowel Disease (IBD). We assessed a known screening tool, as well as developed and validated a novel screening tool, to detect nutrition risk in outpatients with IBD. METHODS AND STUDY DESIGN: The Saskatchewan IBD-Nutrition Risk (SaskIBD-NR Tool) was developed and administered alongside the Malnutrition Universal Screening Tool (MUST). Nutrition risk was confirmed by the IBD dietitian (RD) and gastroenterologist (GI). Agreement between screening tools and RD/GI assessment was computed using Cohen's kappa. RESULTS: Of the 110 patients screened, 75 (68.2%) patients had Crohn's Disease and 35 (31.8%) ulcerative colitis. Mean BMI was 26.4 kg/m2 (SD=5.8). RD/GI assessment identified 23 patients (20.9%) at nutrition risk. The SaskIBD-NR tool classified 21 (19.1%) at some nutrition risk, while MUST classified 17 (15.5%). The SaskIBD-NR tool had significant agreement with the RD/GI assessment (k 0.83, p<0.001), while MUST showed a lack of agreement (k 0.15, p=0.12). The SaskIBD-NR had better sensitivity (82.6% vs 26.1%), specificity (97.7% vs 87.4%), positive predictive value (90.5% vs 35.3%), and negative predictive value (95.5% vs 81.7%) than the MUST. CONCLUSION: The SaskIBD-NR, which assesses GI symptoms, food restriction, and weight loss, adequately detects nutrition risk in IBD patients. Broader validation is required.

An Examination of Diet for the Maintenance of Remission in Inflammatory Bowel Disease.

Diet has been speculated to be a factor in the pathogenesis of inflammatory bowel disease and may be an important factor in managing disease symptoms. Patients manipulate their diet in attempt to control symptoms, often leading to the adoption of inappropriately restrictive diets, which places them at risk for nutritional complications. Health professionals struggle to provide evidence-based nutrition guidance to patients due to an overall lack of uniformity or clarity amongst research studies. Well-designed diet studies are urgently needed to create an enhanced understanding of the role diet plays in the management of inflammatory bowel disease. The aim of this review is to summarize the current data available on dietary management of inflammatory bowel disease and to demonstrate that dietary modulation may be an important consideration in managing disease. By addressing the relevance of diet in inflammatory bowel disease, health professionals are able to better support patients and collaborate with dietitians to improve nutrition therapy.

Synbiotic therapy: a promising new adjunctive therapy for ulcerative colitis.

Prebiotic and probiotic therapies are new strategies being used to treat gastrointestinal diseases. Recent evidence suggests that the administration of select prebiotics and probiotics, alone or in combination (the latter called "synbiotic" therapy) may improve the clinical outcome of patients with ulcerative colitis. We report a case of a pediatric ulcerative colitis patient who showed increased length of remission, resolution of symptoms, and improved quality of life following the administration of synbiotic therapy. The literature supporting the use of prebiotic, probiotic, and synbiotic therapies in adult ulcerative colitis is also reviewed.