Introduction

Food related symptoms are frequently reported by patients with IBS and can occur within 30 minutes of a meal. The mechanisms underlying food-related symptoms likely involve local immunological reactions to food. To date, most research has focused on the distal GI tract and data on the proximal small intestine – the segment most exposed to food- is scarce.

Aims & Methods

Aim: To characterize the duodenal microenvironment, permeability and systemic inflammatory markers in patients with frequent food-related symptoms.
Methods: Cross-sectional study of a cohort of patients with IBS and age- and sex-matched healthy controls (HC). Symptoms were assessed using the Rome IV diagnostic questionnaire and daily symptoms were assessed daily using visual analog scales (reported as the mean of two weeks). Markers of systemic inflammation were assessed using Roche Cobas c502 (high-sensitivity C-reactive protein (hs-CRP)), Sysmex XN-9100 (white blood cell (WBC) count) and Thermo Fisher Phadia1000 (IgE and tryptase) on a Phadia 1000 platform. Small intestinal permeability was measured ex vivo in Ussing chambers, in vivo via the laculose/mannitol ratio in a 2-hour urine collection (LMR, 5g lactulose and 1g mannitol ) and by quantifying epithelial gaps using confocal laser endomicroscopy (CLE). Duodenal immune cell composition was quantified histologically and eosinophilic cationic peptide (ECP) and tryptase content were measured in mucosal lysates. Immune cell activity was assessed by quantifying the spontaneous release of tryptase and eosinophil-derived neurotoxin in biopsy supernatants. Assessed variables are presented in the table. Group-wise comparisons, correlation with daily symptoms and principal component analysis (PCA) were performed.

Results

Thirty-five patients with Rome IV IBS and 15 age- and sex-matched HC were included in this analysis. Patients with IBS had significantly higher tryptase content in the duodenal mucosa than HC (299 ng/mg total protein vs 143 ng/mg, p = 0.016) – none of the other variables were different between patients and HC. Based on the frequency of food-related pain, we subdivided patients with IBS into patients with frequent food-related pain (n = 22, overall ≥80% of abdominal pain episodes food-related) and patients with infrequent food-related pain. Using unsupervised PCA, patients with frequent and infrequent food-related symptoms did not cluster separately. There was no difference in duodenal eosinophil or mast cell counts between frequent and infrequent food-related pain. The proportion of patients with comorbid functional dyspepsia (FD) was not different between groups (45% vs 55%, p = 0.6). In the subgroup with frequent food-related symptoms, daily abdominal pain severity correlated significantly with LMR (r = 0.59, p = 0.02), hs-CRP (r = 0.69, p < 0.01) and WBC count (r = 0.55, p <0.01). In contrast, none of the duodenal variables correlated with pain severity.

Conclusion

The content of duodenal tryptase was significantly higher in patients with IBS than in HC. We found no differences in the duodenal micro-environment between patients with frequent and infrequent food-related symptoms. Among patients with IBS, the subgroup with the most frequent food-related symptoms showed significant correlations of daily pain severity and duration with hs-CRP, WBC and LMR, suggesting a possible pathophysiological role of systemic immune activation and small intestinal permeability. These preliminary findings warrant a larger-scale assessment.

Introduction

The human gut microbiome consists of a diverse range of microorganisms, including not only bacteria but also viruses, archaea and fungi. Among these, bacteria have been shown to have a significant impact on the health or disease status of the host. However, despite increasing evidence for the role of fungi in liver disease, inflammatory bowel disease and cancer, little is known about the interactions between bacteria and fungi.

Aims & Methods

In this study, we aimed to investigate in depth the interkingdom relationship between fungal and bacterial communities in the gut of healthy monozygotic and dizygotic twins using a novel merging analysis method. Faecal samples from 106 twin pairs were analysed using 16S rRNA gene sequencing for bacteria and ITS sequencing for fungi. To enable a comprehensive analysis of the interactions between these two microbial communities, we adapted a novel merging normalisation method and linked it to systematic dietary and environmental characteristics.

Results

The implementation of the merging normalisation method allowed for an in-depth comparison of the fungal and bacterial communities independent of the low read counts. In direct comparison, bacteria were significantly more abundant and diverse than fungi, with Bacteroides and Prevotella being the most dominant bacterial genera. Within the fungal community, Candida was the most abundant genus in the cohort, followed by Geotrichum, while Saccharomyces was less abundant. Other fungal genera were detected sporadically between individuals. Most bacterial taxa showed a negative correlation with both Candida and Geotrichum at some level of abundance. For example, Bacteroides showed no antagonism towards Candida when its relative abundance was below 5%, whereas genera such as Prevotella (rho=-0.16, p=0.02), Alistipes (rho=-0.16, p=0.02) and Faecalibacterium (rho=-0.17, p=0.01) showed antagonistic interactions with Candida at relative abundances as low as 0.1%. These correlations were calculated across different abundances of the interacting fungi and bacteria, showing that negative associations increased with higher abundance (up to rho=-0.6 for Alistipes). An interkingdom network analysis further revealed a complex dynamic involving the three most abundant genera - Bacteroides, Prevotella and Candida - which showed mutually antagonistic relationships.

Conclusion

The implementation of the novel, easy-to-use merging analysis provided an in-depth view of the interactions between bacterial and fungal communities in the human gut, which are predominantly antagonistic in nature. The bacterial community appears to use several mechanisms to protect the gut environment from fungal colonisation.

Disclosure

Nothing to disclose

Introduction

Prospective evidence of the long-term efficacy of endoscopic submucosal dissection (ESD) for T1 colorectal cancer (CRC) is insufficient.

Aims & Methods

We aimed to evaluate long-term ESD outcomes for T1 CRC, focusing on the risk stratification criteria and necessity of additional surgery.
This large-scale, multicenter, prospective cohort study was conducted by Hiroshima GI Endoscopy Research Group. All consecutive patients who underwent colorectal ESD between January 2014 and December 2018 were included, and those with pathologically confirmed T1 CRC were analyzed. Patients were classified into low-risk and high-risk groups based on histopathological risk factors for lymph node metastasis in JSCCR guidelines. High-risk patients were categorized into those who underwent additional surgery (surgery group) and those who were followed up without surgery (follow-up group).

Results

Among 2357 patients who underwent ESD for 2478 early colorectal neoplasms, 431 were diagnosed with T1 CRC. Ten recurrences (2.6%) and five T1 CRC-associated deaths (1.3%) occurred in the high-risk group, with none in the low-risk group. Five-year cumulative overall and local recurrence rates were significantly higher in the follow-up versus surgery group (7.7% and 1.9%; P=0.019 versus 6.4% and 0%; P<0.001), with no local recurrence in the surgery group. Five-year overall survival was significantly worse in the follow-up group (79.5% and 95.2%; P<0.001), while no significant difference was found in 5-y disease-specific survival (98.5% and 98.5%; P=0.447).

Conclusion

No recurrence or mortality occurred in the low-risk group, suggesting that intensive surveillance may be unnecessary for these patients after curative ESD. Additional surgery could prevent local recurrence for high-risk T1 CRC, supporting a risk-based treatment approach.