Introduction

Gut microbiome alterations are known to be one of the pathogenic pathways of irritable bowel syndrome (IBS), mainly in its post-infectious form (PI-IBS) ¹. To date, untargeted therapeutic approaches have obtained conflicting results in patients with PI-IBS ^2,3
Gut microbiome testing are emerging as a promising diagnostic tool to target microbiota and offer a personalized therapeutic strategy, but their real value is still unknown.

Aims & Methods

Our aim is to evaluate whether a personalized approach based on gut microbiome testing is an effective strategy for PI-IBS.
In this pilot study, we included consecutive patients with PI-IBS, diagnosed according to the Rome IV guidelines⁴, referring at our outpatient microbiome clinic in 2022.
All patients underwent a commercially available stool microbiome testing (XMICROGem from XBIOGem) based on 16S rRNA analysis and performed as already described⁵. Then, patients received a targeted therapy based on results of the gut microbiome testing, with the aim of restoring balance among the bacterial subpopulations of the gut microbiota. Non-adsorbable antibiotics were used to downregulate the abundance of pathobionts, while prebiotics and probiotics were given to boost the abundance of specific taxa and/or to compete with gut pathobionts. Patients were followed up to 12 weeks after the end of therapy.
We collected the following data of patients: age, gender, presence of gastrointestinal (GI) symptoms (assessed with the GSRS); specific characteristics of gut microbiome (alpha diversity, abundance of Proteobacteria, Firmicutes, Bacteroidetes, Bifidobacteria, Lactobacilli, Akkermansia, and short-chain fatty acid producers including Lachnospiraceae, Faecalibacterium, Roseburia, Butyrivibrio); specific therapy given after testing, including non-adsorbable antibiotics, prebiotics, and probiotic strains. The primary outcome was the resolution of at list one symptom, while secondary outcomes were the resolution of more than one (if present) and all of them at 12 weeks.

Results

Thirteen patients were enrolled in the study period (8 males, 5 females, mean age 31 years-old). Of them, 9 (69%) had IBS-D and 4 (31%) IBS-C. Nine patients (69%) had bloating, and 10 (71%) had abdominal pain at baseline. At gut microbiome testing: three (23%) patients presented with low alpha diversity, three (23%) with high abundance of Proteobacteria, five (38%) of Firmicutes. Seven (54%) patients presented with low abundance of SCFA-producing bacteria, eight (62%) of Akkermansia and nine (69%) of Bifidobacteria.
Patients were treated with the following non-adsorbable antibiotics: rifaximin in nine (69%) patients, and paromomicin in four (31%) patients. The following prebiotics and probiotic strains were used after antibiotics: multispecies probiotics in five patients (38%), Bifidobacterium-based probiotics in five patients (38%), Lactobacillus-based probiotics in eight patients (54%), and Escherichia coli Nissle 1917 in 2 (15%) patients; inulin and psyllium were used in nine (69%) patients.
At 12-week follow-up, 12 patients (93%) experienced an improvement of symptoms, with five of them (38%) experiencing a total remission of symptoms.

Conclusion

A precision medicine approach based on gut microbiome testing may be a promising strategy to treat PI-IBS. Well designed, randomized and larger studies are needed to confirm our preliminary findings.

References

1. Downs, I. A., Aroniadis, O. C., Kelly, L. & Brandt, L. J. Postinfection Irritable Bowel Syndrome: The Links Between Gastroenteritis, Inflammation, the Microbiome, and Functional Disease. J Clin Gastroenterol 51, 869–877 (2017).
2. Lee, Y. Y., Annamalai, C. & Rao, S. S. C. Post-Infectious Irritable Bowel Syndrome. Curr Gastroenterol Rep 19, 56 (2017).
3. Jin, Y. et al. Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota. J Gastroenterol Hepatol 33, 443–452 (2018).
4. Drossman, D. A. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Gastroenterology 150, 1262-1279.e2 (2016).
5. De Maio, F. et al. Characterization of gut microbiota in patients with metabolic syndrome candidates for bariatric/metabolic surgery: Preliminary findings of a multi-center prospective study. Diabetes Res Clin Pract 180, 109079 (2021).

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma.
A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai.
G.C. has received personal fees for acting as advisor for Ferring Therapeutics.
All other authors have no conflicts of interest to disclose.

Introduction

Use of Non-steroidal anti-inflammatory drugs (NSAIDS) is associated with gastrointestinal (GI) injury with the degree of damage depending on dose, duration of treatment, concomitant medication, and patient risk profile(Goldstein & Cryer, 2015; Lanza et al., 1999, 2018; Yeomans et al., 2018).

Aims & Methods

Previously, we have reported that the probiotic strain Bifidobacterium breve, Bif195 (DSM 33360) at doses of 50x10⁹ and 100x10⁹ CFU/day alleviated aspirin-induced mucosal injury in the small intestine(Mortensen et al., 2019) and the stomach(Damholt et al., 2021), respectively. Here, we report results from an additional randomized controlled double-blind trial (RCT) of Bif195 in a lower dose on NSAID-induced mucosal injury. Although the trials were not directly comparable in design, they provided an opportunity to evaluate the effect of different doses of Bif195. In this study the NSAID was ibuprofen given in a dose of 800 mg/day for 6 weeks. Video Capsule Endoscopy was used to assess small-intestinal damage and to calculate Lewis score throughout the study(Gralnek et al., 2008).

Results

A total of 160 subjects (63% women) were included in the full analysis set (randomized, consumed at least one dose of trial product and with available efficacy data for the primary endpoint) with mean ± SD body mass index of 26.8 ± 6.1 kg/m² and age of 27.3 ± 5.5 years. There were no effects of the Bif195 intervention on any of the primary and secondary endpoints. Low-dose Bif195 did not reduce ibuprofen-induced damage in the small intestine compared to placebo as evaluated by Lewis score (AUC, mean ± SEM 2358 ± 137 vs 2208 ± 123, p=0.474). It is noteworthy that the degree of damage associated with ibuprofen was markedly lower than that associated with aspirin in an earlier study (AUC, mean ± SEM 4351 ± 574)(Mortensen et al., 2019). Bif195 was well-tolerated, and no treatment-related adverse events were recorded. We conclude that the lower level of damage induced by ibuprofen compared to aspirin in combination with low dose Bif195, might have had an impact on the ability of the trial to identify an effect.

Conclusion

In summary, of three individual RCTs examining the effects of Bif195 on aspirin- and ibuprofen-induced gut mucosal injury, two showed benefits while one employing a lower dose of Bif195 in individuals exposed to ibuprofen failed to show benefit. While these studies suggest that the effects of Bif195 may be dose related this should be interpreted with caution due to the differences in injurious agent and trial design. The trial was registered at Clinicaltrials.gov: NCT04447924.

References

Damholt, A. B. et al. (2021). The probiotic bifidobacterium breve, BIF195, supports the defense against aspirin-induced gastrointestinal mucosal damage. Circulation, 144(SUPPL 1).
Goldstein, J. L., & Cryer, B. (2015). Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies. Drug, Healthcare and Patient Safety, 7, 31–41.
Gralnek, I. M. et al. (2008). Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Alimentary Pharmacology & Therapeutics, 27(2), 146–154.
Lanza, F. L. et al. (2018). Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial. Clinical and Experimental Gastroenterology, Volume 11, 169–177.
Lanza, F. L. et al. (1999). Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen. Alimentary Pharmacology and Therapeutics, 13(6), 761–767.
Mortensen, B. et al. (2019). Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers. Gastroenterology, 157(3), 637-646.e4.
Yeomans, N. D. et al. (2018). Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial. Alimentary Pharmacology & Therapeutics, 47(11), 1453–1463.

Disclosure

SE and AD are employed at Chr. Hansen A/S.

Introduction

The extent of gastric atrophy(GA) is closely related to the incidence of Intestinal-type gastric cancer (GC). According to the Kimura-Takemoto classification, determining whether the atrophy extends beyond the cardia is key to assess the extent of GA. However, there is significant difficulty in determining whether the cardia is atrophied under endoscopy.

Aims & Methods

This study developed a novel artificial intelligence (AI)-assisted white light endoscopy system for identifying the cardia part and diagnosing cardia atrophy . In this multicenter study, patients undergoing upper gastrointestinal endoscopy at 5 hospitals in China were prospectively included between November 2022 and December 2024. Among them, a total of 895 patients from 2 units were assigned to the training and validation sets (292 with cardia atrophy and 603 without cardia atrophy) to establish a cardia atrophy diagnostic model. 220 patients from our unit (84 with cardia atrophy and 136 without cardia atrophy) were included in the internal test set. Additionally, a total of 354 patients from 3 other units were included in the external test set (106 with cardia atrophy and 248 without cardia atrophy). In the internal and external test sets, 3 senior and 3 junior endoscopists made online diagnoses, comparing the performance differences between physicians with different levles of experience and the AI-assisted cardia atrophy detection system.

Results

This study established a AI-assisted cardia atrophy diagnostic model and tested its diagnostic performance with multicenter image data in internal and external tests. In the internal test dataset, the accuracy, sensitivity, and specificity of the AI-assisted system were 0.927, 0.941, and 0.919, respectively, with a PPV of 0.878, NPV of 0.962, and AUC of 0.967. In the external test dataset, the accuracy, sensitivity, and specificity were 0.918, 0.894, and 0.931 respectively, with a PPV of 0.874, NPV of 0.943, and AUC of 0.953. Further comparison of the diagnostic efficiency of the AI-assisted system with endoscopists of different levels of experience revealed that both in the internal and external test set, the diagnosis accuracy, sensitivity, specificity, PPV, and NPV of the AI-assisted system were all higher than those of senior endoscopists. TheAI-assisted cardia atrophy diagnostic ROC curve area (AUC) was 0.967 and 0.953 in the internal and external test sets, respectively. Heat map analysis further showed a high consistency between theAI-assisted system and endoscopists in cardia atrophy diagnosis.

Conclusion

Our newly developed AI-assisted cardia atrophy diagnostic system shows superior performance in identifying cardia atrophy compared to senior endoscopists, and can be used to guide white light endoscopic judgment and targeted biopsies for cardia atrophy.

Introduction

Intestinal ultrasound (IUS) has proven to be a valuable tool for accurately detecting intestinal damage and characterizing disease behavior in Crohn’s disease (CD). IUS scoring systems for CD activity have been developed, however all the studies had methodological flaws. Therefore, studies comparing and validating the existing IUS scores in CD patients are required.

Aims & Methods

In this study, we aimed to compare two main existing scores, Bowel Ultrasound Score (BUSS) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ileal CD using the simplified endoscopic activity score for CD (SES-CD).
An observational cross-sectional study was performed to evaluate the disease activity in adult CD patients with ileal involvement between November 2019 and February 2024. All patients had undergone ileocolonoscopy and IUS, the time interval between the two procedures was lower than 10 days. Receiver operating characteristic (ROC) curve analyses was performed for BUSS and IBUS-SAS to predict SES-CD ≤2 for CD.

Results

Total 56 adult patients with ileal CD were included in the study, 38 patients (67.9%) were male, the median age was 40.5 (IQR 26-46.75) years and the median duration of the disease was 8.4 (IQR, 4.93-10.29) years. In the endoscopically remission (SES-CD ≤2) group; the median BUSS was 2.63 (IQR 2.12-3.45) and the median IBUS-SAS was 14 (IQR, 11.3-18.4), while in the endoscopically active (SES-CD >2) group; the median BUSS was 5.67 (IQR, 3.47-7.76) and the median IBUS-SAS was 49.7 (IQR, 23.3-72.65). The median BUSS and median IBUS-SAS in the endoscopically remission group were significantly lower than those of the endoscopically active group (p< 0.001, for both). The cut-off value for BUSS to determine endoscopic remission (SES-CD ≤2) was 3.9 (AUC: 0.839, 95% CI: 0.737-0.941, sensitivity: 92%, specificity: 73%, p < 0.001), while the cut-off value for IBUS-SAS to establish endoscopic remission (SES-CD ≤2) was 24.4 (AUC: 0.871, 95% CI: 0.780-0.962, sensitivity: 100%, specificity: 73%, p < 0.001).
There was a very high positive correlation between BUSS and IBUS-SAS (r=0.914, p<0.001), a high positive correlation between BUSS and SES-CD (r=0.659, p<0.001), a moderate positive correlation between BUSS and CRP (r=0.577, p<0.001). There was a high positive correlation between IBUS-SAS and SES-CD as well as IBUS-SAS and CRP (r=0.728, p<0.001 and r=0.657, p<0.001 respectively).

Conclusion

In this study, we found that the most accurate cut-off value for BUSS was 3.9 and the most accurate cut-off value for IBUS-SAS was 24.4 in CD patients with endoscopic remission (SES-CD ≤2) group. Also, we have confirmed that both BUSS and IBUS-SAS significantly correlate with endoscopic activity in a real-world cohort.

Introduction

The BELCOMID study recruited immune mediated inflammatory disease (IMID) patients during the COVID19 pandemic. Patients were evaluated before vaccination, after onset of the vaccination campaign and after onset of booster vaccinations. Clinical data, Nucleocapsid(N-)antibodies and Spike(S-)antibodies were assessed.

Aims & Methods

Current subgroup analysis aimed to firstly, explore factors associated with N-/S-antibody response in IMID patients with different COVID19 vaccination status. Five patient groups were identified. G1: no vaccination before the vaccination campaign, G2: complete baseline vaccination, G3: 1 booster, G4: 2 boosters, G5: patients refusing every vaccine even after the booster campaign. We report on influence of IMID treatment and smoking status.
Secondly, we explored influence of SARS-CoV2 infection and vaccination on IMID flare-up.

Results

Demographics of 2165 recruited IMID patients are shown in Table.
After baseline vaccination (G2) odds of N-seroconversion were higher in patients treated with combined IMM/TIMT (OR2.52, p=0.023). No other association with N-seroconversion was found.
Mean S-antibody titre increased progressively from G2 to G4. After completed baseline vaccination (G2), odds of S-antibody seroconversion were lower in those treated with TIMT (OR0.28, p=0.0079) particularly rituximab (OR0.0354, p<0.001), IMM (OR0.276, p<0.001), combined IMM/TIMT (OR0.156, p<0.001) and systemic steroids (OR0.183, p<0.001). IMID flare prior to vaccination was associated with lower risk of S-seroconversion (RR0.94, p<0.001). By contrast, mean S-titre was higher for those treated with antiIL23 (mean ratio 2.17, p=0.011) and vedolizumab (mean ratio 1.84, p<0.001) in G2.
After 1 booster (G3), lower odds of S-seroconversion remained with rituximab (OR0.0368, p<0.001), IMM (OR0.222, p=0.0014), combined IMM/TIMT (OR0.15, p<0.001) or systemic steroids (OR0.0637, p<0.001). Vedolizumab was associated with lower odds of being in the lowest S-titer quartile (OR0.206, p<0.001). Odds for S-antibody seroconversion with anti-TNF were higher compared to rituximab both for patients in G2 (OR26.3, p<0.001) and G3 (OR27.5, p<0.001).
Patients who received 2 boosters (G4) all had S-seroconversion and no IMID treatment modality was associated with higher odds of being in the lowest quartile.
After baseline vaccination (G2) smokers had higher risk of being in the lowest S-antibody titer quartile (RR1.45, p=0.0098). This observation persisted after 1 booster (G3)(RR1.42, p=0.0122) but was no longer noticed after 2 boosters (G4).
After start of booster vaccinations, 25.17% of patients had experienced IMID flare-up in the previous months. No significant association between IMID flare-up rate and previous SARS-CoV2 infection was found. There was no increased risk of IMID flare-up with additional booster vaccination. However, patients who received 2 booster vaccines showed a lower RR for IMID flare-up compared to those who only received 1 booster (RR0.70, p=0.0067).

	G1 (N: 2144)	G2 (N: 1532)	G3 (N: 1283)	Group 4 (N: 147)	Group 5 (N: 40)
Mean age (SD)	44.6 (35.5)	46.9 (30.8)	46.6 (32.7)	51.0 (15.7)	39.4 (14.4)
Male/female	1088 (51.0%)/1047 (49.0%)	794 (51.9%)/737 (48.1%)	661 (51.6%)/621 (48.4%)	80 (54.4%)/67 (45.6%)	24 (60.0%)/16 (40%)
Active smoker	369 (17.2%)	261 (17.0%)	201 (15.7%)	24 (16.3%)	12 (30.0%)
TIMT (targeted treatment)	1580 (73.7%)	1232 (80.4%)	1073 (83.6%)	119 (81.0%)	38 (95.0%)
IMM (immunomodulator)	456 (21.3%)	311 (20.3%)	225 (17.5%)	39 (26.5%)	8 (20.0%)
IMM+TIMT combined	263 (12.3%)	197 (12.9%)	152 (11.8%)	24 (16.3%)	8 (20.0%)
Recent systemic steroids	229 (10.7%)	91 (5.94%)	59 (4.60%)	6 (4.08%)	4 (10.0%)

Conclusion

Certain immune-modulating treatment modalities and smoking may blunt serologic COVID19 vaccination responses. However, this is overcome by repeated booster vaccination without increased risk of IMID flare-up.

Disclosure

The BELCOMID study group received research grants from following pharmaceutical companies: Almirall, Roche, Janssen, Pfizer, Eli Lilly, Amgen, Biogen, Mylan, LEO Pharma. These companies had no role in study design, conduct nor reporting of results.

Introduction

Perianal fistulising Crohn’s disease (PFCD) affects up to 20% of patients with Crohn’s Disease (CD). PFCD can cause pain, purulent discharge and faecal incontinence, leading to significant morbidity and reduction in quality of life. The use of biologic therapy, antibiotics and surgical intervention remain the mainstay of management of perianal fistulas.

Aims & Methods

This study aims to review current practices in the management of PFCD across two large tertiary IBD centres. This retrospective cohort study assessed adult patients with PFCD between two tertiary Australian hospitals between 2006 to 2024. Patients with PFCD were identified using prescribing data. CD phenotype, therapy and fistula-related data were extracted. Biologic choice and therapeutic drug monitoring, antibiotic choice and duration, surgical intervention, and length of stay in hospital were monitored. Cross-sectional disease activity of perianal fistulizing disease was assessed at the time of data collection using clinical fistula symptom grade and radiological assessment were available. Clinical remission was defined as fistula symptom grade of 1 or less. Radiological remission was defined by healing fistula tracts or no active inflammation seen on MRI. The study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC19145).

Results

Gender Male, n Female, n Age, y, median (IQR)	n = 57 30 27 40 (31-54)
Active Smoker, n (%)	14 (24.5)
Median length of clinical follow up, months, n (IQR)	46.5 (23.8-72.3)
Antibiotics Prescribed Metronidazole, n treated (%) Amoxicillin / Clavulanic acid, n treated (%) Others, n treated (%)	47 (68.1) 13 (27.7) 9 (4.2)
Duration of Antibiotics Metronidazole, median duration, days (IQR) Amoxicillin / Clavulanic acid, median duration, days (IQR) Others, median duration, days (IQR)	5 (5-7) 5 (5-10) 14 (7-14)
Biologic therapy Total patients on biologic therapy, n (%) Infliximab, n (%) Adalulimab, n (%) Ustekinumab, n (%)	56 (98.2) 43 (75.4) 11 (19.3) 2 (3.5)
Therapeutic Drug Monitoring (Infliximab) Infliximab level performed, n (%) Subtherapeutic (Infliximab level <10), n (%) Active disease and subtherapeutic (Infliximab level <10), n (%)	37 (86%) 30 (81.1%) 12 (40%)
Remission status Clinical Remission, n (%) - Defined as Fistula symptom grade of 1 or less Radiological Remission, n (%) - Defined as healing fistula tracts or no active inflammation seen on MRI	48 (84.2) 33 (57.8)
Subtherapeutic Therapeutic Drug Monitoring (All biologic agents) In Remission, n (%) Active Disease, n (%)	18 (56.2) 14 (43.8)

Table 1. Baseline characteristics

57 patients (median age, 40 years (31-54); 52.6% male) with PFCD were included in the study and followed over a median duration of 46.5 months (23.8-72.3). There were a total of 157 individual surgical procedures over the period, 2.75 per patient, most of which (94.2%) were examination under anaesthesia. Antibiotic therapy was dispensed for either perianal sepsis or an actively draining fistula in 26 patients, 2.65 number of courses per patient. The most common antibiotic prescribed was Metronidazole (68.1%), followed by Amoxicillin / Clavulanic acid (27.7%). The median duration of antibiotic therapy was 5 days (5-7) for Metronidazole and 5 days (5-10) for Amoxicillin / Clavulanic acid. There were 56 (98.2%) patients on biologic therapy. The most common biologic agent was Infliximab (75.4%), followed by Adalimumab (19.3%) and Ustekinumab (3.5%). At the time of analysis, 48 patients (84.2%) were in clinical remission and 33 patients (57.8%) were in radiographical remission. In patients treated with infliximab, 37/43 (86%) had therapeutic drug monitoring performed. Amongst these, 30 (81.1%) had subtherapeutic levels (defined as Infliximab level < 10), with 12/30 (40%) of patients having active PFCD.

Conclusion

Across two tertiary IBD centres, management of PFCD is variable and not in keeping with current guidelines. Short courses of antibiotic therapy were used, and the majority of patients had subtherapeutic drug levels when tested. Optimising outcomes for patients with PFCD requires awareness of best practice and a multidisciplinary team approach.