Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.

Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

INTRODUCTION: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.

Herpes simplex virus colitis mimicking acute severe ulcerative colitis: a case report and review of the literature.

A 60-year-old female patient with longstanding left-sided ulcerative colitis presented with symptoms mimicking an acute flare and developed a colonic perforation shortly after starting steroid treatment. Following left hemicolectomy and Hartmann's procedure, rescue treatment with infliximab was started. Within a few days, the patient developed hepatic failure. Histology and immunohistochemistry of the specimen revealed extensive necrotizing herpes simplex virus colitis, and liver biopsy demonstrated herpes simplex virus hepatitis. Sixteen days after admission, the patient died from multiorgan failure. This compelling case of severe herpes simplex virus colitis raises awareness of a rare but potentially detrimental infection in patients with inflammatory bowel disease.

Comparison of transnasal esophagoscopy and sedated esophagogastroduodenoscopy in the assessment of laryngopharyngeal reflux.

OBJECTIVE: Transnasal esophagoscopy (TNE) in the awake patient and esophagogastroduodenoscopy (EGD) in sedation are both used in the assessment of laryngopharyngeal reflux (LPR). The objective of this study was to compare these two endoscopic methods in contributing to the diagnosis of LPR. METHODS: This study included 54 patients presenting with signs and symptoms suspicious for LPR, which were examined both by TNE and EGD. The contribution of each method to the diagnosis of LPR was evaluated separately and then compared with each other. RESULTS: In detecting LPR, TNE showed a significant higher sensitivity (94% vs. 60%) and accuracy (93% vs. 59%) than EGD, but their specificity was equal (50% each). The most common pathologic findings in both methods were a hiatal hernia (70% vs. 48%) and gaping cardia (69% vs. 24%), followed by peptic esophagitis (41% vs. 24%). CONCLUSION: The value of EGD is limited in the workup of LPR, as sedation tends to mask the subtle findings in this kind of reflux disease.

Visible abdominal distension in functional gut disorders: Objective evaluation.

BACKGROUND: Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation). METHODS: A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35. KEY RESULTS: (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent). CONCLUSIONS AND INFERENCES: In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity.

Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial.

BACKGROUND: Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS. METHODS: This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 µg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization. DISCUSSION: Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. METHODS: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. RESULTS: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. CONCLUSION: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT00488631].

Stimulatory MAIT cell antigens reach the circulation and are efficiently metabolised and presented by human liver cells.

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation. DESIGN: We used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD). RESULTS: MAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner. CONCLUSION: Our findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.

Faecal calprotectin increases the diagnostic yield in patients with suspected small bowel disease - a multicenter retrospective cohort study.

AIM OF THE STUDY: Diagnosing small bowel pathology is challenging, and the diagnostic yield of small bowel capsule endoscopy is highly variable. Faecal calprotectin is a non-invasive intestinal inflammation marker that could be used as a selection tool to identify patients who might benefit from small bowel capsule endoscopy and increase its diagnostic yield. This study aimed to investigate the value of faecal calprotectin in detecting small bowel lesions in an unselected patient population. METHODS: We performed a retrospective analysis of consecutive patients who underwent small bowel capsule endoscopy at the University Hospital Basel and the University Medical Clinic Cantonal Hospital Baselland, Switzerland, between 2010 and 2018. Patients without faecal calprotectin testing were excluded from the analysis. The primary endpoint was the presence of a clinically significant small bowel finding. RESULTS: Patients with positive faecal calprotectin results were more likely to have small bowel findings (66.7% vs 39.4%; P = 0.007). The optimal faecal calprotectin cut-off to identify clinically significant small bowel lesions was 63 µg/g with 78.3% (95% confidence interval: 66.7-87.9) sensitivity, 47.9% (33.3-62.8) specificity, 1.50 (1.1-2.0) positive and 0.45 (0.3-0.8) negative likelihood ratios, 68.4% (61.6-74.4) positive and 60.5% (47.3-72.4) negative predictive values, and 65.0% overall accuracy. Faecal calprotectin performed best in patients with suspected inflammatory bowel disease, with 66.7% (48.2-82.0) sensitivity, 70.6% (44.0-89.7) specificity, 2.27 (1.0-4.9) positive and 0.47 (0.3-0.8) negative likelihood ratios, 81.5% (67.0-90.5) positive and 54.5% (39.7-68.6) negative predictive values, and 71.4% overall accuracy. CONCLUSION: Faecal calprotectin testing increases the diagnostic yield of small bowel capsule endoscopy and may help identify patients at risk of small bowel disease.

[Interventional endoscopy in hepatico-pancreatico-biliary disease]. / Moderne Behandlungsoptionen an Gallenwegen und Pankreas in der interventionellen Endoskopie.

Interventional endoscopy in hepatico-pancreatico-biliary disease Abstract. Interventional endoscopy has undergone an exciting evolution in recent years, especially in the treatment of hepatico-pancreatico-biliary disease. However, novel endoscopes have also improved diagnostics through direct visualization of the biliary tract and the pancreatic duct, including targeted biopsy-sampling of suspicious endoluminal lesions. The use of cholangioscopy also allows for lithotripsy of complex gallstones under direct visualization. In patients with malignant biliary obstruction, endosonography(EUS)-guided insertion of novel lumen-apposing metal stents allow for extraanatomical access to intra- or extrahepatic bile ducts, if traditional transpapillary stent insertion fails. Especially in patients with altered anatomy e. g., after surgery, EUS-guided transgastric drainage may be the most sensible approach. Using similar techniques, EUS-guided drainage of the pancreatic duct is also possible. Local tumor therapy may be achieved with novel endoscopic retrograde cholangiography-guided catheter-based radiofrequency ablation and photodynamic therapy. In chronic pancreatitis, similar to biliary disease, methods of endoluminal diagnosis, lithotripsy, and transgastric drainage may also be applied. This article provides an overview of novel endoscopic techniques and methods that are available in hepatico-pancreatico-biliary disease.

Value of Transnasal Esophagoscopy in the Workup of Laryngo-Pharyngeal Reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) can display a variety of symptoms, and upper endoscopy is occasionally used for its investigation. The aim of the present study was to determine the value of transnasal esophagoscopy (TNE) in the workup of LPR. METHODS: In 200 consecutive patients with suspected LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring (PHM) and transnasal esophagoscopy (TNE) were carried out and rated according to the Horvath Score. RESULTS: In the investigation of LPR, TNE showed a sensitivity, specificity and accuracy of 96%, 85% and 95%, respectively. The most common pathologic TNE findings in LPR patients were an insufficient cardia, hiatal hernia, lymphoid follicles and visible reflux. CONCLUSIONS: TNE is a supportive method in the workup of LPR, which can display the underlying pathology and directly affect therapeutic decisions.

Evaluation of Oropharyngeal pH-Monitoring in the Assessment of Laryngopharyngeal Reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) is a prevalent disorder. The aim of the present retrospective cohort study was to evaluate oropharyngeal pH-monitoring using a novel scoring system for LPR. METHODS: In a total of 180 consecutive patients with possible LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring and transnasal esophagoscopy were carried out for further investigation. RESULTS: In our series, 99 (55%) patients had severe LPR, 29 (16%) cases presented with moderate and 23 (13%) with mild severity, 9 (5%) subjects revealed neutral values, and 7 (4%) individuals were alkaline, while 13 (7%) patients had no LPR. In detecting LPR, the sensitivity, specificity and accuracy of oropharyngeal pH-monitoring was 95%, 93% and 94%, respectively. CONCLUSION: Oropharyngeal pH-monitoring is a reliable tool in the assessment of LPR, but the pH graphs have to be precisely analyzed and interpreted in context with other validated diagnostic tests.

Technical feasibility, clinical effectiveness, and safety of esophageal stricture dilation using a novel endoscopic attachment cap in adults with eosinophilic esophagitis.

BACKGROUND AND AIMS: The BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a new device that allows optical and tactile feedback during stricture dilation of the upper GI tract. We evaluated the technical feasibility, clinical efficacy, and safety of a 1-time esophageal stricture dilation using the BougieCap in adults with eosinophilic esophagitis (EoE). METHODS: EoE patients prospectively included in the Swiss EoE Cohort were dilated with the BougieCap for esophageal strictures (esophageal diameter, ≤14 mm) and stricture-related symptoms. Symptoms were assessed before and 2 weeks after a single dilation session using the validated Eosinophilic Esophagitis Activity Index Patient Reported Outcomes instrument (score ranges from 0 to 100 points). RESULTS: Fifty patients (70% men; median age, 41 years; median disease duration, 4 years; 50% treated with swallowed topical corticosteroids, 10% with proton pump inhibitors, 14% with combined swallowed topical corticosteroids plus proton pump inhibitors, 14% with elimination diet, 12% without antieosinophil therapy) were evaluated. Endoscopic bougienage was technically successful in 100%. The median esophageal diameter increased from 12 mm (interquartile range [IQR], 12-13) to 16 mm (IQR, 16-16; P < .001). Median symptom severity dropped from 32 points (IQR, 27-41) to 0 (IQR, 0-10; P < .001) at 2 weeks postdilation. In 1 patient the BougieCap was temporarily lost after stricture dilation in the hypopharynx but could be retrieved. No severe adverse events were reported. CONCLUSIONS: In adults with EoE, endoscopic treatment of esophageal strictures using the BougieCap is technically feasible and safe and offers significant symptomatic improvement in the short term.

A novel scoring system for evaluating laryngopharyngeal reflux.

OBJECTIVE: Although laryngopharyngeal reflux (LPR) is a common condition in daily practice, no gold standard exists for its diagnosis. The objective of this study was to establish a simple and reliable scoring system for evaluating LPR consisting of both subjective and objective criteria. METHODS: This retrospective study includes 124 patients presenting with symptoms of LPR. In all patients, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH monitoring (PHM) and transnasal oesophagoscopy (TNE) were performed and rated in a special scoring system. RESULTS: A Horvath Score of 4-5 for severe LPR was found in 76 patients (61%), a score of 2-3 for non-severe LPR in 38 patients (31%) and a score of 0-1 for non-existing LPR in 10 patients (8%) by combining the 4 validated diagnostic methods. CONCLUSION: The proposed scoring system qualifies as a simple and reliable tool for evaluating LPR in daily practice, directly impacting patient management.

Treatment Algorithms for Crohn's Disease.

BACKGROUND: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. SUMMARY: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD - especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update.

BACKGROUND: Patient care in ulcerative colitis (UC) remains challenging despite an array of established treatment options and emerging new therapies. The management of UC therapy should be guided by the endoscopic extent of inflammation, disease severity, and prognostic factors of poor outcome. Complete remission, defined as durable symptomatic and endoscopic remission without corticosteroid therapy, is the desired treatment goal. SUMMARY: This review focuses on treatment recommendations for different clinical scenarios in moderate-to-severe UC: Active UC of any extent not responding to aminosalicylates, steroid-dependent UC, steroid-refractory UC, immunomodulator-refractory UC, and acute severe UC. Comprehensive treatment algorithms for daily clinical practice were developed based on published guidelines and current literature. Key Messages: While current treatment options including a number of biologicals and small molecules have evolved UC treatment to achieve sustained remission in a majority of patients, upcoming treatment options with different molecular pathways and different modes of actions will further increase the need for personalized medicine.

Position statement on the use of biosimilars in inflammatory bowel disease.

Biologics are effective and have a good safety profile in the treatment of inflammatory bowel disease. Biosimilars have recently become available as treatment option. They are biological agents that are highly similar to the original biologic compound in their structure, biological activity, efficacy and safety. This position paper summarises current knowledge on biosimilars and presents its statements on regulatory issues and clinical situation in order to provide clinicians adequate information for them to reach informed and appropriate shared decision-making with their patients.

Abdominal distension after eating lettuce: The role of intestinal gas evaluated in vitro and by abdominal CT imaging.

BACKGROUND: Some patients complain that eating lettuce, gives them gas and abdominal distention. Our aim was to determine to what extent the patients' assertion is sustained by evidence. METHODS: An in vitro study measured the amount of gas produced during the process of fermentation by a preparation of human colonic microbiota (n = 3) of predigested lettuce, as compared to beans, a high gas-releasing substrate, to meat, a low gas-releasing substrate, and to a nutrient-free negative control. A clinical study in patients complaining of abdominal distention after eating lettuce (n = 12) measured the amount of intestinal gas and the morphometric configuration of the abdominal cavity in abdominal CT scans during an episode of lettuce-induced distension as compared to basal conditions. KEY RESULTS: Gas production by microbiota fermentation of lettuce in vitro was similar to that of meat (P = .44), lower than that of beans (by 78 ± 15%; P < .001) and higher than with the nutrient-free control (by 25 ± 19%; P = .05). Patients complaining of abdominal distension after eating lettuce exhibited an increase in girth (35 ± 3 mm larger than basal; P < .001) without significant increase in colonic gas content (39 ± 4 mL increase; P = .071); abdominal distension was related to a descent of the diaphragm (by 7 ± 3 mm; P = .027) with redistribution of normal abdominal contents. CONCLUSION AND INFERENCES: Lettuce is a low gas-releasing substrate for microbiota fermentation and lettuce-induced abdominal distension is produced by an uncoordinated activity of the abdominal walls. Correction of the somatic response might be more effective than the current dietary restriction strategy.