Introduction

Real-time symptom assessment provides a detailed understanding of the dynamic interplay between gastrointestinal symptoms in irritable bowel syndrome (IBS) and potential triggers, including affect and environmental factors. This study evaluates the association between abdominal pain and potential triggers over time in IBS patients with and without comorbidities, using the Experience Sampling Method (ESM) as a real-time, ecologically valid measurement method.

Aims & Methods

In this prospective, observational multicenter study, as part of the DISCOvERIE project, we included 215 Rome IV IBS patients (80% female; mean age 42.1) from six European countries, categorized into 103 IBS-alone, 67 IBS-mental (anxiety/depression), 16 IBS-somatic (fibromyalgia/chronic fatigue syndrome), and 29 IBS-multicomorbid patient subgroups. Participants scored abdominal pain and affect using an 11-point Numeric Rating Scale and environmental factors using ESM at up to ten random moments each day over seven consecutive days. Linear mixed-effects models analyzed the associations between abdominal pain and these potential triggers, both concurrently and predictively (trigger scores lagged by one time point, maximum of 90 minutes), in each subgroup.

Results

ESM assessment completion rate was 63%. Regarding affect triggers, abdominal pain was significantly correlated with concurrent positive and negative affect in all IBS groups (p<0.02), while significant lagged associations were only found within IBS-mental for positive affect (p=0.02) and within IBS-alone and IBS-multicomorbid for negative affect (p<0.001). Regarding environmental triggers, abdominal pain was significantly associated with concurrent ‘feeling comfortable in situation’ within IBS-alone, IBS-mental and IBS-multicomorbid (p<0.001), concurrent ‘feeling of pleasantness of company’ (p=0.01) and being alone (versus with somebody, p=0.01) within IBS-alone, and eating since the last ESM-assessment within IBS-alone (p=0.04) and IBS-multicomorbid (p=0.002). No significant lagged associations or correlations with location, activity, alcohol consumption, and nicotine use were found.

Conclusion

Our results demonstrate that in IBS patients, real-time abdominal pain is significantly associated with environmental and affect triggers, with both positive and negative affect correlating with abdominal pain irrespective of mental comorbidities. Moreover, fewer triggers predict abdominal pain over time, underscoring the importance of in-the-moment assessments. This study highlights the value of ESM in accurately identifying symptom triggers, thereby enhancing personalized healthcare in IBS.

Disclosure

MB, LV, MH, IM, SM, MRB, and DD declare no conflicts of interests. DJ has received research funding from public-private partnership grants of Top Knowledge Institute (TKI) Agri&Food and Health Holland, by the Carbokinetics program as part of the NWO-CCC Partnership Program, and by Organic A2BV/Mothersfinest BV. DK has received research funding from ZonMw, MLDS, UEG, Rome Foundation, Horizon Europe, Horizon 2020, Grunenthal, Allergan and speaker’s fee from Dr Falk (paid to host institute).

Introduction

Subjectively reported sleep disturbances are common in IBS¹, as are psychological comorbidities². Whilst sleep and psychological disorders are clearly linked, it has been demonstrated that sleep disturbances amongst IBS patients appear to exist independently of psychological factors³, raising the potential for sleep as a novel intervention target in IBS. Developing our understanding of the role and associations of sleep within the disease experience of IBS patients could lead to better treatment.

Aims & Methods

We aimed to compare the characteristics of patients with IBS according to the quality of their sleep. Participants were recruited from the NIHR research register ContactME-IBS. We collected data for demographics, gastrointestinal symptoms^4,5,6, psychological health⁷, quality of life^8,9, and impact on work and daily activities¹⁰using validated questionnaires among adults with Rome IV IBS. We dichotomised the cohort according to whether they were good or poor sleepers, defined by a Pittsburgh sleep index score >5¹¹. We compared the characteristics of the two groups to explore significant associations.

Results

Of 341 respondents with Rome IV IBS, 287 (84.16%) were poor sleepers. A significantly higher proportion of poor sleepers had been diagnosed with IBS for 5 years or more (82.2% vs 66.7% p=0.009). A greater proportion of good sleepers had a university or postgraduate level of education (59.3% vs 41.1% p=0.014), though this did not meet our threshold for statistical significance. Poor sleepers had a significantly higher burden of severe somatisation, nearly fivefold that of good sleepers (60.3% vs 13% p=<0.001). Poor sleepers reported higher levels of anxiety and depression symptoms. Amongst the good sleepers, none had abnormal depression scores. Poor sleepers experienced greater impairment of their work activities, and were more adversely affected in their home and social activities (p=<0.001 across all analyses). Though not statistically significant, poor sleepers reported higher IBS symptom severity. There was no statistically significant difference between poor and good sleepers in relation to their IBS subtype.

Table 1. Characteristics of Individuals with Rome IV IBS according to the quality of their sleep.

Conclusion

Individuals with Rome IV IBS who report poor sleep have significantly higher levels of somatisation and psychological comorbidity and are more adversely affected in both their work and personal lives, compared with those who report good sleep. Our findings could support the potential of sleep as an intervention target in the management of IBS.

References

1. Tu Q et al. Neurogastroenterol Motil. 2017;29(3).
2. Zamani M et al. Alimentary pharmacology & therapeutics. 2019;50(2):132-43.
3. Koloski NA et al. Alimentary pharmacology & therapeutics. 2021;54(5):627-36.
4. Palsson OS et al. Gastroenterology. 2016:S0016-5085 (16) 00180.
5. Whitehead W et al. Rome III: The functional gastrointestinal disorders, 3rd editionVirginia: Degnon Associates Inc. 2006:835-53.
6. Labus JS et al. Alimentary pharmacology & therapeutics. 2004;20(1):89-97.
7. Spiller R et al. Alimentary pharmacology & therapeutics. 2010;32(6):811-20.
8. Patrick DL et al. Digestive diseases and sciences. 1998;43:400-11.
9. Drossman DA et al. Official journal of the American College of Gastroenterology| ACG. 2000;95(4):999-1007.
10. Reilly M et al. Alimentary pharmacology & therapeutics. 2004;20(4):459-67.
11. Buysse DJ et al. Psychiatry research. 1989;28(2):193-213

Introduction

Spasmolytic polypeptide expressing metaplasia (SPEM) is a cell repair lineage and is a very important phenotype of gastric mucosal injury and precancerous lesion.
Previously, parietal cells loss is considered as the first step and followed with chief cells transdiffernation to induce SPEM. But whether chief cells initial loss cause SPEM
needs to be further investigation. Acidic mammalian chitinase (CHIA) belongs to the 18 glycosidase family and is highly expressed in the chief cells. Our previous study showed that CHIA deficiency in the chief cells is the key event to induce SPME to progress to gastric cancer (Liu et al., DDW 2023 and 2024). However, the molecular role of CHIA in the development of SPEM is need further investigated.

Aims & Methods

Electron microscopy, qRT-PCR and single-cell sequencing (scRNA-seq) technology, as well as histopathological and immunofluorescence (IF) stainning with specific markers were performed in chief cells specific CHIA knockout mouse model (CHIA^rox/rox-GIF-Dre) and wild-type mice(CHIA^rox/rox), and in CHIA over - expression mice (CHIA ^rox/rox - GIF - Dre + rAAv - CHIA) and the control group (CHIA ^rox/rox - GIF - Dre + rAAv - control).

Results

Compared with CHIA^rox/rox mice, histological analysis and scRNA-seq technology data showed that loss of chief cells with increased M2 macrophage infiltration and final SPEM formation, but remaining of parietal cells in CHIA^rox/rox-GIF-Dre mice. Electron microscopy showed CHIA deficiency in mice resulted in endoplasmic reticulum was dilated and swollen, as well as the mitochondrial membrane was discontinuous of chief cells, followed with the accumulation of endoplasmic reticulum stress marker, including PERK, XBP-1, eIF2α/P-eIF2α, and GRP78, together with upregulation of pyroptosis-related marker, including NLRP3, ACS, GSDMD, NEK7, Caspase1, Caspase11, IL-1β, and IL-18, which was detected by qRT-PCR. These data indicating that target CHIA deletion caused chief cells pyroptosis. Furthermore, qRT-PCR analysis showed that CHIA deficiency caused the activation of IL33/IL-13 circuit in the mucosa of mice. Moreover, double immunofluorescence staining confirmed that upregulation and colocalization of IL-33 induced M2 macrophage polarization markers, including F4/80 and CD163⁺ with NLRP3 in the base of gastric mucosal of CHIA^rox/rox-GIF-Dre mice when compared with CHIA^rox/rox mice.Notably, CHIA ^rox/rox - GIF - Dre + rAvv - CHIA mice reversed the above process compared with controls.

Conclusion

Chief cells specific CHIA deficiency resulted in endoplasmic reticulum stress mediate NLRP3 inflammasome activation to induce chief cells proptosis.
Chief cells initial loss is sufficient and the key step to activate IL-33/ST2-M2 macrophage polarization axis to induce SPEM, which is independent of parietal cells loss.