Introduction

Crohn's disease (CD) is a complex chronic intestinal inflammatory disease with unknown etiology¹. Gut microbiota is involved in the bile acid metabolism in the intestine and the regulation of intestinal mucosal immunization to maintain intestinal homeostasis². The histological changes in the intestinal mucosa of CD are closely related to impaired intestinal barrier function^3-5. Abnormal gut microbiota and metabolic disorders can destroy the normal intestinal barrier function and intestinal homeostasis, thereby continuously aggravating the inflammatory reactions^6,7.

Aims & Methods

To further explore the related factors affecting the incidence and provide essential guidelines for clinical prevention and treatment of CD, the prospective case-control study conducted a multi-omics analysis of gut microbiota, fecal bile acid profiles, serum cytokines and intestinal barrier function in patients with active CD, patients in remission and normal controls.

Results

The study found that CD patients had unique gut microbiota and fecal bile acid profiles compared with normal controls, which were related to the disease activity. The beneficial bacteria represented by Romboutsia were positively correlated with the concentrations of fecal secondary bile acids, while negatively correlated with the concentrations of primary bile acids. When patients were active, their gut-beneficial bacteria decreased, affecting the bile acid metabolism. The variation of CD patients' bile acid profile was increased. The production of secondary bile acids was decreased. The levels of proinflammatory cytokines in peripheral blood were increased, such as FC, ESR, CRP and HBP, with P values all below 0.001. And the CD active group had significantly higher levels of IL-6, IL-8, IL-10 and IL-1β than those in remission, with P values of <0.001, 0.005, 0.04 and 0.044, respectively. The intestinal physical barrier and mucosal barrier were damaged with disease activity of CD.

Conclusion

The study suggested that the occurrence and development of CD might be caused by the interaction between gut microbiota and the metabolic product bile acid, which leads to the consequence of immune response in the body and the damage to the intestinal barrier.

References

1. Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis. 2022;16(3):472-89.
2. Leonardi I, Gao IH, Lin WY, et al. Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity. Cell. 2022;185(5):831-46.e14.
3. Leibovitzh H, Lee SH, Raygoza Garay JA, et al. Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis. Gut. 2023;72(8):1462-71.
4. Rath T, Atreya R, Bodenschatz J, et al. Intestinal Barrier Healing Is Superior to Endoscopic and Histologic Remission for Predicting Major Adverse Outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial. Gastroenterology. 2023;164(2):241-55.
5. Maddipatla SC, Kolachala VL, Venkateswaran S, et al. Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn's Disease. Inflamm Bowel Dis. 2023;29(2):274-85.
6. Caparrós E, Wiest R, Scharl M, et al. Dysbiotic microbiota interactions in Crohn's disease. Gut Microbes. 2021;13(1):1949096.
7. Leibovitzh H, Lee SH, Xue M, et al. Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn's Disease. Gastroenterology. 2022;163(5):1364-76.e10.

Disclosure

All authors declared no potential conflicts of interest with respect to the study.

Clinical Case Summary

A 2-week-old full-term female infant presented to the pediatric emergency department with five days of vomiting, loss of appetite, and bloody stools. Initially fed a cow milk-based formula, she did not gain weight. On admission, she appeared lethargic, with vital signs indicating low blood pressure, elevated heart rate, increased respiratory rate, and a body temperature of 36.6°C. Cold extremities, delayed capillary refill time, and marbled skin were noted. Abdominal examination revealed distension without peritonitis or skin discoloration, and no hepatosplenomegaly was present. Laboratory tests showed metabolic acidosis with an elevated anion gap and high lactate levels. The patient vomited stomach contents and fecal material, prompting the use of a nasogastric tube, which drained extensively. An abdominal x-ray revealed diffuse pneumatosis in the intestinalis without bowel perforation. Managed in the pediatric intensive care unit with nil per os, total parenteral nutrition, and empirical parenteral antibiotics. Blood and urine cultures, as well as stool PCR testing for common viral and bacterial pathogens, were negative. The infant showed improvement after two weeks of conservative treatment, including abdominal X-rays, which revealed normal gas patterns without signs of pneumatosis intestinalis. Introduction of an amino acid-based formula was well-tolerated without recurrence of symptoms.

Pneumatosis intestinalis mainly occurs during the neonatal period and is more common among preterm neonates. The main etiology is necrotizing enterocolitis (NEC). However, it can present among term neonates, infants, children, and even adults. The differential diagnosis is wide, including cow’s milk protein allergy, infectious diseases, trauma, ischemia, child abuse, and intestinal failure.
The working diagnosis of this case was pneumatosis intestinalis secondary to milk protein allergy, which was managed successfully and conservatively without any invasive procedure.

References

1. Im J, Anjum F. Pneumatosis Intestinalis. [Updated 2023 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564381/
2. Abramov A, Luks VL, De Bie F, Hwang R, Allukian M 3rd, Nace GW Jr. Pneumatosis intestinalis in children beyond the neonatal period: is it always benign?. Pediatr Surg Int. 2022;38(3):399-407
3. Overman RE Jr, Criss CN, Gadepalli SK. Necrotizing enterocolitis in term neonates: A different disease process? J Pediatr Surg. 2019 Jun;54(6):1143-1146.
4. Narumoto S, Sakamoto S, Uchida H, et al. Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation. Pediatr Transplant. 2018 Feb;22(1).
5. Reppucci ML, Nolan MM, Cooper E, et al. Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?. J Pediatr Gastroenterol Nutr. 2023;76(5):560-565.

Introduction

There is an ongoing paradigm shift toward serology-based diagnosis of celiac disease (CeD). It is essential to target potential endoscopies for those most likely to benefit. Anemia is a common symptom of CeD that may warrant further investigations, but the prevalence and clinical relevance of endoscopic findings in anemic CeD patients remain unclear.

Aims & Methods

The aim of this study was to compare the prevalence of upper and lower endoscopic findings between anemic patients and non-CeD controls, and to identify predictors of significant findings in CeD patients. Medical data, including upper and lower endoscopy findings, were collected from 162 CeD patients and 350 controls. Binary logistic regression analysis was used to identify predictors of findings.

Results

CeD patients were younger (median 49 vs 66 years, p<0.001) and had fewer risk factors such as smoking (14% vs 25%, p<0.001), alcohol abuse (4% vs 14%, p<0.001), chronic comorbidities (55% vs 83%, p<0.001), and previous malignancies (1% vs 8%, p=0.002).
In comparison of upper endoscopy findings, CeD patients had fewer significant findings (21% vs 53%, p<0.001), H. Pylori positive gastritis (6% vs 19%, p<0.001), gastric ulcers (0% vs 5%, p=0.006), and atrophic gastritis (3% vs 9%, p=0.005) compared to the controls.
Twenty-four patients and 208 controls had undergone lower endoscopy with celiac patients more frequently demonstrating significant findings (54% vs 28%, p=0.008), non-specific inflammation (21% vs 1%, p<0.001) and colorectal cancer (25% vs 9%, p=0.018).
Predictors of significant upper endoscopy findings in CeD patients were older age (OR 1.03, 95% CI 1.01-1.05), age >50 (2.44, 1.18-5.06), co-existing chronic conditions (3.45, 1.53-7.78), gastrointestinal symptoms (2.31, 1.07-4.98), and use of acetylsalicylic acid (2.38, 1.01-5.06), and of colonoscopy findings older age (1.01, 0.99-1.04), co-existing conditions (3.48, 1.12-10.8), and gastrointestinal symptoms (4.73, 1.34-16.7).

Conclusion

CeD patients had fewer findings on upper endoscopy but, despite being younger and having fewer risk factors, showed more findings on lower endoscopy compared to controls. In older CeD patients presenting with anemia, lower endoscopy should be strongly considered.

Introduction

The development of the double balloon enteroscopy (DBE) system in 2001 and later, the single balloon enteroscopy (SBE) in 2007 allowed direct visualisation, biopsies and therapeutic interventions of lesions in the small bowel. Previous studies comparing these two techniques show mixed results. The aim of this study is to compare the efficacy of single balloon and double balloon enteroscopy with regards to technical success, diagnostic yield, therapeutic success and complication rates.

Aims & Methods

The development of the double balloon enteroscopy (DBE) system in 2001 and later, the single balloon enteroscopy (SBE) in 2007 allowed direct visualisation, biopsies and therapeutic interventions of lesions in the small bowel. Previous studies comparing these two techniques show mixed results. The aim of this study is to compare the efficacy of single balloon and double balloon enteroscopy with regards to technical success, diagnostic yield, therapeutic success and complication rates.

Results

There were 82 patients in the DBE group and 45 patients in the SBE group. The main indications were suspected GI bleeding (DBE 41.5% vs. SBE 48.9%), iron deficiency anemia (DBE 9.8% vs. SBE 4.4%) and small bowel lesions (DBE 28.0% vs. SBE 44.4%) with positive imaging modality, either from prior capsule endoscopy or radiological imaging. Majority of the cases via antegrade approach (DBE 67.1% vs. SBE 77.8%). We found no significant difference in the technical success (DBE 95.1% vs. SBE 97.8%, p=0.46), diagnostic success (DBE 65.9% vs. SBE 77.8%, p=0.36) and the therapeutic success rate (DBE 61.1% vs. SBE 51.4%, p=0.09) between the groups. Complications occurred in one case from each group (mucosal tear).

Conclusion

The efficacy of DBE and SBE are similar with regards to technical success, diagnostic yield, therapeutic success and complication rate.

Introduction

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published an update of its guideline in 2021, in which vancomycin or fidaxomicin replaced metronidazole as the preferred first-line treatment option for non-severe Clostridioides difficile infection (CDI). This decision was controversially discussed since outcome data in this particular patient group remains limited. The IBIS study aimed to close this evidence gap.

Aims & Methods

The IBIS multicentre cohort enrolled patients with an index episode of CDI between August 2017 and September 2020. The primary endpoint was event-free survival (EFS), defined as response to treatment with metronidazole or vancomycin within ten days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections.

Results

​Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within ten days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event-free. The Cox proportional hazards model revealed differences in EFS for the overall population and both sub-groups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% Cl 0.33-0.65]; non-severe: HR 0.39; [95% Cl 0.24-0.60]; severe: HR 0.52; [95% Cl 0.28-0.95]).

Conclusion

Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared to metronidazole across all severity levels.

References

1. Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Review of Gastroenterology & Hepatology. 2010;4(4):409-16.
2. van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clinical Microbiology and Infection. 2021;27:1-21.
3. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.
4. Manthey CF, Epple H-J, Keller K-M, Lübbert C, Posovszky C, Ramharter M, et al. S2k-Leitlinie Gastrointestinale Infektionen der Deutschen Gesellschaft für
5. Zar FA, Bakkanagari SR, Moorthi KMLST, Davis MB. A Comparison of Vancomycin and Metronidazole for the Treatment of Clostridium difficile–Associated Diarrhea, Stratified by Disease Severity. Clinical Infectious Diseases. 2007;45(3):302-7.
6. Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: Update of the Treatment Guidance Document for Clostridium difficile Infection. Clinical Microbiology and Infection. 2014;20:1-26.