Chronic Poor Sleep is Associated with Increased Disease Activity in Patients with Ulcerative Colitis: Prospective Observational Study in Japan Hideaki Oyama, Rintaro Moroi, Atsushi Sakuma, Yusuke Shimoyama, Hiroshi Nagai, Takeo Naito, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune Journal of Crohn's and Colitis.2024;[Epub] CrossRef
Inflammatory bowel diseases comprising Crohn’s disease and ulcerative colitis have emerged as global diseases. Multiple distinct therapeutic mechanisms have allowed us to increase our rates of achieving remission and reducing permanent disease-related morbidity. However, there is limited data to inform relative positioning of different therapies. This review will summarize existing literature on use of clinical decision models to inform relative efficacy of one therapeutic mechanism compared to the other given individual patient characteristics. It will also demonstrate the value of serologic, transcriptomic (from biopsies), and microbiome-based biomarkers in identifying which therapy is most likely to work for a given patient. We will review the existing gaps in the literature in this field and suggest a path forward for future studies to better inform patient care, incorporating the principles of precision medicine in the management of inflammatory bowel disease.
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Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn’s disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Background/Aims Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.
Methods One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.
Results Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.
Conclusions The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.
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Which biomarkers best reflect the degree of inflammation in Crohn’s disease? Jihye Park Intestinal Research.2024; 22(1): 1. CrossRef
Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn’s disease small bowel lesion in capsule endoscopy Teppei Omori, Miki Koroku, Shun Murasugi, Ayumi Ito, Maria Yonezawa, Shinichi Nakamura, Katsutoshi Tokushige Intestinal Research.2024; 22(4): 464. CrossRef
Background/Aims The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity.
Methods A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn’s disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings.
Results Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed.
Conclusions IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.
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A novel serum biomarker of endoscopic mucosal healing in inflammatory bowel disease Hyoun Woo Kang Intestinal Research.2024; 22(1): 3. CrossRef
Background/Aims Transabdominal ultrasonography (US) helps evaluate Crohn’s disease (CD) activity. We investigated whether the US could predict subsequent adverse outcomes for patients with CD in clinical remission.
Methods This single-center retrospective study included patients with CD in clinical remission who underwent US between April 2011 and April 2021, focusing on the predictability of subsequent adverse outcomes within 5 years. We used the US-CD, which was calculated using multiple US findings. Predictive variables were assessed using Cox proportional hazards regression analysis, and the predictive value was evaluated using receiver operating characteristic curves.
Results Seventy-three patients were included. During a median follow-up of 1,441 days (range, 41–1,825 days), 16.4% (12/73) experienced clinical relapse, 9.6% (7/73) required endoscopic balloon dilation (EBD), 58.9% (43/73) required enhanced treatment, and 20.5% (15/73) underwent surgery. In the multivariate analysis, US-CD was significantly associated with clinical relapse (P= 0.038) and the need for enhanced treatment (P= 0.005). The area under the receiver operating characteristic curve for predicting clinical relapse and the need for EBD was 0.77 and 0.81, respectively, with US-CD (cutoff value = 11), and that for requiring enhanced treatment was 0.74 with US-CD (cutoff value = 6). Patients with US-CD ≥ 11 demonstrated a significantly higher occurrence of clinical relapse (P= 0.001) and EBD (P= 0.002) within 5 years. Patients with US-CD ≥ 6 experienced a significantly higher likelihood of requiring enhanced treatment (P< 0.001) within 5 years.
Conclusions High US-CD is associated with subsequent adverse outcomes in patients with CD.
Background/Aims Mucosal adaptation of the ileum toward colonic epithelium has been reported in pouchitis in ulcerative colitis (UC); however, the clinical characteristics, endoscopic findings, and outcomes in patients with pouchitis with ileal mucosal adaptation are poorly understood.
Methods This was a single-center retrospective study comprising UC patients treated by proctocolectomy with ileal pouch-anal anastomosis who had undergone pouchoscopy at the University of Tsukuba Hospital between 2005 and 2022. Endoscopic phenotypes were evaluated according to the Chicago classification. High-iron diamine staining (HID) was performed to identify sulfomucin (colon-type mucin)-producing goblet cells (GCs) in pouch biopsies. We compared clinical data between patients with (high HID group) and without > 10% sulfomucin-producing GCs in at least one biopsy (low HID group).
Results We reviewed 390 endoscopic examination reports from 50 patients. Focal inflammation was the most common phenotype (78%). Five patients (10%) required diverting ileostomy. Diffuse inflammation and fistula were significant risk factors for diverting ileostomy. The median proportion of sulfomucin-producing GCs on histological analysis of 82 pouch biopsies from 23 patients was 9.9% (range, 0%–93%). The duration of disease was significantly greater in the high HID group compared to the low HID group. The median percentage of sulfomucin-producing GCs was significantly higher in patients with diffuse inflammation or fistula compared to other endoscopic phenotypes (14% vs. 6.0%, P= 0.011).
Conclusions Greater proportions of sulfomucin-producing GCs were observed in endoscopic phenotypes associated with poor outcomes in UC, indicating patients with pouchitis showing colonic metaplasia of GCs may benefit from early interventions.
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Endoscopic assessment of the J pouch in ulcerative colitis: A narrative review Shintaro Akiyama, Edward L Barnes, Tsubasa Onoda, Naoki Ishikawa, Mamiko Shiroyama, Yuka Ito, David T Rubin, Kiichiro Tsuchiya DEN Open.2025;[Epub] CrossRef
A Comparative Analysis of Clinical Symptoms and Modified Pouchitis Disease Activity Index Among Endoscopic Phenotypes of the J Pouch in Patients With Inflammatory Bowel Disease Shintaro Akiyama, Nathaniel A Cohen, Jacob E Ollech, Cindy Traboulsi, Tina Rodriguez, Victoria Rai, Laura R Glick, Yangtian Yi, Joseph Runde, Russell D Cohen, Kinga B Skowron, Roger D Hurst, Konstantin Umanskiy, Benjamin D Shogan, Neil H Hyman, Michele A Crohn's & Colitis 360.2024;[Epub] CrossRef
Background/Aims Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability.
Methods An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn’s Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn’s disease and ulcerative colitis were considered.
Results In a cohort of 670 respondents the median age was 41 years (range, 32–70 years), with the majority female (78.4%), the majority had Crohn’s disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn’s disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety.
Conclusions Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.
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