Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease.

Views on the clinical presentation and symptomatology of celiac disease have evolved alongside advances in disease detection and understanding of disease pathogenesis. Although historically regarded as a pediatric illness characterized by malabsorption, it is now better viewed as an immune illness of gluten-specific T cells with systemic manifestations affecting all ages. Its broad presentation, including frequent extraintestinal manifestations and asymptomatic disease, contributes to suboptimal disease detection. Adverse symptoms greatly impact patient quality of life and can result from chronic gluten exposure in untreated disease or those poorly responsive to the gluten-free diet. They can also present as acute symptoms after episodic gluten exposure. Functional gastrointestinal disease is a common comorbidity. Biomarkers like interleukin-2 that are highly sensitive and specific for celiac disease highlight a role for gluten-specific T cells in acute gluten symptomatology. A mechanistic understanding of symptoms will inform approaches to better measure and treat them effectively.

Measurements of Duodenal Mucosal Integrity Are Altered in Celiac Disease.

Altered barrier function is a part of celiac disease (CeD) pathophysiology that we currently cannot reliably measure. Catheter-based mucosal integrity (MI) is an endoscopic technology that has identified altered esophageal barrier function in esophageal disease.1 The aim of this study was to evaluate feasibility, safety, and clinical utility of measuring duodenal integrity with an MI catheter in patients with and without CeD.

Avoidant/Restrictive Food Intake Disorder Characteristics and Prevalence in Adult Celiac Disease Patients.

Background and Aims: The objective of this study was to identify the prevalence of avoidant/restrictive food intake disorder (ARFID) in patients with celiac disease (CD) and assess metabolic complications, disease control, diet adherence, and correlation with symptom and quality-of-life metrics. Methods: This was a retrospective study of 137 adult patients with CD who completed an ARFID survey in the CD clinic between 2018 and 2020. Demographics, clinical results, standardized diet assessment, and results of Celiac Disease Symptom Diary and Impact of a Gluten-free Diet Questionnaire were reviewed. The primary outcome measured was the rate of suspected ARFID based on patient-reported survey responses. Results: Seventy-eight patients (57%) met suspected ARFID criteria. There were no differences in age, gender, body mass index, micronutrient deficiencies, or bone disease in those with or without ARFID. Patients with ARFID did not have a difference in biopsy activity or better adherence to a gluten-free diet compared with non-ARFID patients. Food and social burden on Impact of a Gluten-free Diet Questionnaire was most predictive of ARFID. Conclusion: ARFID is common and has a high impact in patients with CD. Although some eating behavior is certainly due to their CD, there was no distinct difference in disease control between those with or without suspected ARFID, suggesting these maladaptive behaviors are not necessary for disease control. We did not find increased metabolic complications, but this was a 2-year snapshot. We need to further understand the social and food impacts on patients who score high on this survey to prevent further deficiencies and impaired, long-term detrimental eating behaviors.

Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study.

INTRODUCTION: Smoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD. AIMS: We aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation. METHODS: In this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow <0.31). The primary outcomes were intervention satisfaction and match rates between NMR and medication choice. RESULTS: The baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects. CONCLUSION: MIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.

Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease.

Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.

Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn's Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling.

INTRODUCTION: Biomarkers are needed in inflammatory bowel disease (IBD) to help define disease activity and identify underlying pathogenic mechanisms. We hypothesized that serum metabolomics, which produces unique metabolite profiles, can aid in this search. OBJECTIVES: The aim of this study was to characterize serum metabolomic profiles in patients with IBD, and to assess for differences between patients with ulcerative colitis (UC), Crohn's disease (CD), and non- IBD subjects. METHODS: Serum samples from 20 UC, 20 CD, and 20 non-IBD control subjects were obtained along with patient characteristics, including medication use and clinical disease activity. Non-targeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS/MS) optimized for basic or acidic species and hydrophilic interaction liquid chromatography (HILIC/UPLC-MS/MS). RESULTS: In total, 671 metabolites were identified. Comparing IBD and control subjects revealed 173 significantly altered metabolites (27 increased and 146 decreased). The majority of the alterations occurred in lipid-, amino acid-, and energy-related metabolites. Comparing only CD and control subjects revealed 286 significantly altered metabolites (54 increased and 232 decreased), whereas comparing UC and control subjects revealed only 5 significantly altered metabolites (all decreased). Hierarchal clustering using significant metabolites separated CD from UC and control subjects. CONCLUSIONS: We demonstrate that a number of lipid-, amino acid-, and tricarboxylic acid (TCA) cycle- related metabolites were significantly altered in IBD patients, more specifically in CD. Therefore, alterations in lipid and amino acid metabolism and energy homeostasis may play a key role in the pathogenesis of CD.

Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered body composition, such as low muscle mass, which affects clinical outcomes. Body composition changes in overweight patients with IBD are less understood. The study aim was to determine the prevalence of sarcopenic overweight and obese patients in a cohort of patients with IBD starting new anti-tumor necrosis factor-α therapy and examine differences in response. METHODS: This is a retrospective review of patients with IBD starting a new anti-tumor necrosis factor-α medication that had computed tomography within 3 months of initiation. L3 vertebral slice was used for segmentation of body composition and identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH vitamin D, and body mass index at anti-tumor necrosis factor-α initiation and at 6 months were collected. Outcomes included hospitalization, need for surgery, or new biological medication. RESULTS: Ninety patients were studied. Forty-one of ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P < 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did not predict outcomes in the cohort but was the only significant predictor of need for surgery in overweight and obese subjects (P = 0.002). CONCLUSIONS: Almost half of our cohort was sarcopenic. Most of these patients are normal or overweight and would not be identified as malnourished by traditional measures. Sarcopenia was a predictor of surgery in patients with a body mass index ≥ 25. Identification of sarcopenia has implications for medical nutrition therapy as typically efforts are focused on underweight patients.