Introduction

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract and about 50% of patients develop liver function disorders of different severity in their course. There is unknown cause directly leading to the symptoms of liver damage, one of the suggested causes is impaired mucosal barrier and the associated increased intestinal permeability to bacterial and nutritional antigens and toxins.

Aims & Methods

The aim of the study was to assess the effect of the severity and location of inflammatory lesions in the gastrointestinal tract in the course of IBD on intestinal mucosal barrier disorders and the occurrence of symptoms of liver damage. To assess the degree of mucosal barrier impairment, the intestinal and liver fatty acid-binding proteins (I-FABP and L-FABP) concentrations were assessed, which are sensitive markers of mucosal damage and to assess the degree of liver damage, the fibroblast growth factor (FGF-19) concentrations assessment and laboratory and imaging results. For IBD severity evaluation, the clinical activity scoring indexes and serum tumour necrosis factor alpha (TNF-alpha) concentrations were assessed.
There were 20 children with Ulcerative Colitis (UC, 12 boys, 8 girls, mean age: 16.0 yrs, range: 7.5 – 18) and 20 with Crohn's Disease (CD, 10 boys, 10 girls, mean age: 14.8 yrs, range: 6.3 – 18) and 20 healthy controls enrolled into the study. Serum I-FABP, L-FABP, FGF-19 and TNF-alpha concentrations were assessed at the baseline, before the treatment and after 2 weeks of treatment, using ELISA immunoassays. Statistical analysis was performed with Statistica 13.0 software (TIBCO Software, USA) using Mann-Whitney U test, Wilcoxon signed rank test and Spearman’s correlation rank test.

Results

We found significantly elevated serum I-FABP in active UC group when compared to active CD group and controls (p<0.05), while in inactive UC group and inactive CD group they were comparable to controls (p=NS).
Moreover, serum L-FAPB was significantly increased in active UC group when compared to active CD group and controls (p<0,05) and in inactive UC group when compared to inactive CD group and controls (p<0,05).
When we assessed serum FGF-19 concentrations, we found them significantly increased both in active UC and active CD when comparable to controls (p<0,05) and in inactive UC group when compared to inactive CD group and controls (p<0.05). Additionally, serum FGF-19 concentrations were related to the stage of liver impairment in UC patients.

Conclusion

Increased serum concentrations of I-FABP and L-FABP may be associated to impaired mucosal barrier in IBD. Nevertheless, impaired mucosal barrier may be connected to increased penetration of bacterial and nutritional antigens and toxins and secondary may be related to liver damage. Furthermore, increased serum FGF-19 concentration may be associated with liver damage in the course of IBD in children.

Introduction

The Rutgeerts score, developed three decades ago, is used to assess postoperative endoscopic recurrence in patients with Crohn’s disease (CD) following ileocolonic resection with an end-to-end anastomosis.¹ However, contemporary surgical techniques have introduced new anatomical locations – the ileal body and ileal inlet – which were not accounted for in the original Rutgeerts score.² Additionally, the original Rutgeerts score has demonstrated limited inter-observer reliability.³ To address these limitations, an updated Rutgeerts score, incorporating new anatomical sites, has been proposed. According to the updated Rutgeerts score lesions restricted to the ileal inlet, or the ileal body can no longer be scored as i2a.² While the updated Rutgeerts score offers improved assessment of inflammation after an ileocolonic resection, its reproducibility has not yet been validated.

Aims & Methods

The aim of our study was to evaluate the inter- and intra-observer reliability of the updated Rutgeerts score.
We conducted a retrospective analysis of 183 patients with CD (48% male, median age 36.8 years) who underwent video-recorded ileocolonoscopy within 14 months of resection with ileocolonic anastomosis. An expert reader MF selected and scored videos of ileocolonoscopies, which were then used as the gold standard. After receiving a two-hour training with a set of ten videos eight expert gastroenterologists reviewed and scored the videos. Each reader assessed 92 videos, including 23 videos that were re-scored after at least one month. Based on the gold standard, inter- and intra-rater agreement was calculated across all score levels and for each score level. Inter-rater reliability was assessed using Fleiss' kappa, and intra-rater reliability using Cohen’s kappa, both with and without application of linear weights.

Results

The probability of perfect agreement between two readers across all scores was 0.604 (95% CI: 0.559-0.649). The chance-corrected inter-observer agreement based on Fleiss’ kappa with linear weights across all scores was 0.619 (95% CI: 0.562-0.676). The strongest inter-observer agreement was observed for the i2a score, with a value of 0.736 (95% CI: 0.647-0.826), while the weakest was seen for the i1 score (0.357, 95%CI: 0.225-0.489).
Intra-rater reliability with a Cohen’s kappa was 0.688 (0.609-0.767), and with weighted kappa was 0.831 (0.758-0.868). The overall agreement rate was 76.0% (69.1%-82.0%).

	Categorical		Ordinal
	Estimate	95%CI	Estimate	95%CI
All levels	0.604	(0.559;0.649)	0.882	(0.866;0.897)
i0	0.633	(0.467;0.800)	0.884	(0.824;0.945)
i1	0.357	(0.225;0.489)	0.829	(0.758;0.899)
i2a	0.736	(0.647;0.826)	0.925	(0.896;0.954)
i2b	0.502	(0.439;0.566)	0.856	(0.834;0.877)
i3	0.487	(0.351;0.623)	0.859	(0.798;0.920)
i4	0.715	(0.606;0.824)	0.894	(0.854;0.934)

Table 1. Summary of agreement across score levels: Agreement for all scores and by individual score levels, based on the gold standard (defined as the scores given by an expert reader MF). Categorical agreement reflects only perfect agreement. Ordinal agreement applies linear weights, assigning less weight to minor disagreements and more to larger ones.

Conclusion

The updated Rutgeerts score demonstrates good agreement and substantial inter- and intra-rater reliability in assessing postoperative endoscopic recurrence in CD, supporting its potential for broader adaptation in both clinical practice and research settings.

References

1. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956-963. doi:10.1016/0016-5085(90)90613-6
2. Rivière P, Bislenghi G, Vermeire S, et al. Postoperative Crohn’s Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques. Clin Gastroenterol Hepatol. 2022;20(6):1201-1204. doi:10.1016/j.cgh.2022.02.025
3. Marteau P, Laharie D, Colombel JF, et al. Interobserver Variation Study of the Rutgeerts Score to Assess Endoscopic Recurrence after Surgery for Crohn’s Disease. Journal of Crohn’s and Colitis. 2016;10(9):1001-1005. doi:10.1093/ecco-jcc/jjw082

Introduction

The Pisa EoE Adaptation Questionnaire (PiEAQ) on adaptive behaviors at mealtime significantly improves the correlation between dysphagia scores and histological disease activity (HDA) in eosinophilic esophagitis (EoE) [Reference 1].

Aims & Methods

Whether longitudinal variations of PiEAQ scores (∆PiEAQ) can capture HDA trends following pharmacological treatment of EoE has not been investigated. Consecutive adults (>18 years) with histologically active EoE (i.e., ≥15 eos/high-power field) were prospectively enrolled. Clinical characteristics, HDA, a recall-modified dysphagia symptom questionnaire (mDSQ), esophageal hypervigilance and anxiety scale (EHAS), and PiEAQ (drinking water to push the bolus, lubricating food, chewing for long, and blending food) were recorded longitudinally at baseline (T0) and 12 weeks post-treatment using a 30-day recall period (T1). ROC curve analysis with DeLong test was used to calculate the diagnostic accuracy (AUC) of clinical scores for predicting HDA following treatment. Significance threshold was p<0.05.

Results

Thirty-seven histologically active EoE patients were included (Table 1). The mDSQ, PiEAQ, and EHAS score at baseline were 2.97 (IQR, 2-5), 2.00 (IQR, 1-3), and 21 (IQR, 14– 25), respectively. Following treatment with budesonide orodispersible tablets (72.2%), PPIs (19.6%), dupilumab (5.5%), or milk-free diet (2.7%), histological remission was achieved in 78.4% of patients, while 21.6% remained histologically active. Post-treatment (T1), mDSQ, PiEAQ, and EHAS scores decreased significantly only in patients who achieved histological remission (Table 2 and Figure1). ROC curve analysis showed that a post-treatment reduction of at least 2 adaptive behaviors compared to baseline (∆PiEAQ=-2) had AUC of 85.0%, with 100% specificity and 64% sensitivity for the identification of patients achieving histological remission following treatment. Similarly, a post-treatment reduction of at least 3 points in mDSQ scores compared to baseline (∆mDSQ=-3) had AUC of 81.1% with 100% specificity and 57.7% sensitivity. The non-inferiority analysis showed that the ∆PiEAQ had similar performance to ∆DSQ (DeLong p-value= 0.46). A combined score integrating both ∆PiEAQ and ∆DSQ scores increased the AUC of clinical scores for capturing variations of HDA post-treatment to 90%, with 100% specificity and 73.1% sensitivity for detecting patients achieving histological remission post-treatment (Figure 2).

Conclusion

The PiEAQ is the first questionnaire investigating adaptive behaviors as a standalone domain in EoE. We demonstrated that longitudinal variations in PiEAQ scores are sensitive to HDA variations over time and can monitor histological disease activity trends after treatment. This study confirms that, similar to dysphagia, adaptive behaviors contribute to disease burden in EoE and improve with treatment.

Group	PiEAQ baseline (median)	PiEAQ post-treatment (median)	∆PiEAQ (T1-T0)	p-value
Non-responder (n=8)	2	1.86	-0.14	0.3
Responder (n=29)	1.96	0.138	-1.83	<0.0001
Group	mDSQ baseline (median)	mDSQ post-treatment (median)	∆mDSQ (T1-T0)	p-value
Non-responder (n=8)	2.29	2	+0.16	0.8
Responder (n=29)	3.27	0.33	-2.92	<0.0001
Group	EHAS baseline (median)	EHAS post-treatment (median)	∆EHAS (T1-T0)	p-value
Non-responder (n=8)	17.7	15.8	-1.91	0.9
Responder (n=29)	21.4	10.2	-11.2	<0.0001

References

1. Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Dutch society has witnessed significant societal and demographic changes over the decades. With 28% of the Dutch population having a migration background in 2023, understanding diversity within the gastroenterology workforce is imperative. This study examines the evolution of sex, ethnic, and socio-economic diversity among Dutch gastroenterologists from 2005-2023.

Aims & Methods

This repeated cross-sectional study utilized pseudonymized data from the BIG-register, paired with demographic variables from Statistics Netherlands (CBS), covering the years 2005, 2010, 2015, 2020, and 2023. The total population sample in each year consisted of all individuals registered as gastroenterologists for at least one day in a respective year. Variables such as sex, migration background, year of birth, and parental socio-economic status indicators were analyzed to assess trends and identify factors associated with being a
gastroenterologist. Descriptive and logistic regression analyses were employed to explore these trends and compare generational differences.

Results

The study revealed a narrowing sex gap with an increase in female gastroenterologists (28% to 43% from 2005-2023), particularly among the younger cohort (60% female). However, ethnic diversity has not kept pace, with a decline in the representation of gastroenterologists from migration backgrounds among younger professionals (27% to 18% for gastroenterologists < 1979 and ≥ 1980, respectively). Socio-economic analysis indicated that approximately 75% of gastroenterologists have parents from top-20% assets category.

Conclusion

The gastroenterology field in the Netherlands shows significant advancements in gender diversity, but lags in ethnic and socio-economic diversity. The increasing trend of gastroenterologists from medical families highlights the need for policy adjustments, to ensure access to candidates from more diverse socio-economic backgrounds. Policies should focus much more on promoting comprehensive diversity to enhance healthcare outcomes and reflect the demographic changes within society.

References

1. Stanford FC. The Importance of Diversity and Inclusion in the Healthcare Workforce.
J Natl Med Assoc. 2020;112(3):247-9.
2. Gomez LE, Bernet P. Diversity improves performance and outcomes. J Natl Med
Assoc. 2019;111(4):383-92.
3. Juch A. 100 jaar Maag-Darm-Leverarts in Nederland 1913-20132013. 336 p.
4. Brach C, Fraser I. Reducing disparities through culturally competent health care: an
analysis of the business case. Qual Manag Health Care. 2002;10(4):15-28.
5. Moberly T. Men outnumber women three to one in some specialties. Bmj.
2018;363:k4098.
6. Subramaniam M, Azad N, Wasan SK, Long MT. Equal Opportunity: Women
Representation on Editorial Boards and Authorship of Editorials in Gastroenterology and
Hepatology Journals. Am J Gastroenterol. 2021;116(3):613-6.
7. Dossa F, Baxter NN. The place of women in gastrointestinal medicine and surgery:
the need for progress. Lancet Gastroenterol Hepatol. 2023;8(11):965-6.
8. Kesavarapu K, Schwartz J, Ikonomi E, Ahmad A. What's holding women back? A
review of gender inequality in gastroenterology in the USA. Lancet Gastroenterol Hepatol.
2019;4(12):898-900.
9. Esposito I, Simsek C, Nowak A, Tiniakos D, Equality UEG, Diversity G. United
European Gastroenterology Equality and Diversity Plan. United European Gastroenterol J.
2023;11(5):484-7.

Disclosure

OKB, ABB, PK and LM have no conflict of interests, CJJM is consultant for Douglas (New Zealand) and HLW (The Netherlands). All outside submitted work.

Introduction

The Simple US Score for Crohn's Disease (SIUS-CD) ultrasound index is a tool with high diagnostic accuracy for evaluating Crohn's disease (CD) activity^1,2. This index is distinguished by its prospective and multicenter validation, high interobserver agreement, and simple calculation. However, its usefulness for monitoring treatment response remains uncertain.

Aims & Methods

A prospective study was conducted in adult patients with CD who initiated treatment with Ustekinumab. All participants were evaluated by ultrasound and colonoscopy at baseline and again after 6 months of treatment. Patients who modified their therapy during the study or who presented with an impassable stricture on endoscopy were excluded.
Ultrasound examinations were performed by two gastroenterologists from the Inflammatory Bowel Disease (IBD) Unit with experience in ultrasonography, using Canon Aplio i800 equipment (Canon Medical Systems, Japan). Biological parameters (C-reactive protein [CRP] and fecal calprotectin [FC]) and ultrasound parameters of activity were recorded, with the SIUS-CD index calculated for the segment with the highest activity.
Endoscopy was performed by gastroenterologists from the same IBD Unit with extensive experience in endoscopic indices, using Olympus endoscopes (Olympus, Japan). Endoscopic remission was defined as SES-CD ≤ 3 or a Rutgeerts score < i2. Endoscopic response was considered as a >50% or ≥3-point reduction in SES-CD, or a ≥1-point decrease in the Rutgeerts score. Physicians were blinded to the results of the other test, and no physician performed both evaluations.

Results

A total of 19 patients were included; their baseline characteristics are summarized in Table 1. The median time between ultrasound and colonoscopy was 8 days (IQR = 56.5). Endoscopic response was observed in 9 patients (47.37%), 8 of whom were in endoscopic remission (42.11%).
In patients who achieved remission, SIUS-CD index values decreased significantly compared to those who did not (4.63 vs. 7.63; p < 0.0056). However, in this subgroup, no statistically significant differences were found in CRP (2.77 mg/L vs. 6.14 mg/L; p = 0.08) or FC levels (332.64 µg/g vs. 283.94 µg/g; p = 0.60).
Among patients with endoscopic response, a significant reduction of 3.43 ± 3.55 points in the SIUS-CD index was observed between baseline and 6-month evaluations (p < 0.0099). In contrast, no significant changes were found in patients without endoscopic response (8.46 ± 1.83).

SEX	Male	52,63%
	Female	47,37%
LOCATION	L1	27,78%
	L2	5,56%
	L3	66,67%
PATTERN	B1	36,84%
	B2	47,37%
	B3	15,79%
FECAL CALPROTECTIN	719,13 (DE +/- 784,24)
C - REACTIVE PROTEIN	7,7 (DE+/- 12,43)

Conclusion

According to preliminary results, a 3.4-point reduction in the SIUS-CD index was associated with endoscopic response, suggesting that this ultrasound index may be sensitive to changes following initiation of biological therapy, and could predict both remission and endoscopic response. Ultrasound and endoscopy showed better correlation in assessing disease activity than biomarkers (CRP and FC), supporting follow-up strategies that prioritize imaging techniques over laboratory markers alone.

References

1. Ripollés T., Poza J., Suárez Ferrer C., Martínez-Pérez M.J., Martín-Algíbez A., de las Heras Páez B. Evaluation of Crohn's Disease Activity: Development of an Ultrasound Score in a Multicenter Study. Inflamm Bowel Dis. 2021;27(1):145–154. doi:10.1093/ibd/izaa134
2. Ripollés T., Poza J., Martínez-Pérez M.J., Suárez Ferrer C., Blanc E., Paredes J.M. Assessment of Crohn’s Disease Activity: Validation of a Segmental Simple Ultrasound Score in a Multicenter Study. Inflamm Bowel Dis. 2024. doi:10.1093/ibd/izae213

Introduction

Microscopic colitis (MC) is an inflammatory bowel disease (IBD) that causes chronic non-bloody watery diarrhea and abdominal pain that significantly reduces the quality of life¹. MC can be subdivided into collagenous colitis (CC) and lymphocytic colitis (LC), which are clinically indistinguishable but differ histologically². The activation of immune responses and the alteration of the intestinal epithelial barrier via water channel aquaporin downregulation and crypt hyperproliferation are characteristic features of MC³, often shared by other gastrointestinal disorders, such as “classical” IBD (Crohn’s disease and ulcerative colitis, UC), or irritable bowel syndrome (IBS). Enteric glial cells (EGC) are key regulators of gut homeostasis and epithelial permeability, that respond to inflammation by entering a reactive state, potentially driving epithelial dysfunction. Whether EGC promote resolution or perpetuate inflammation remains unclear.⁴

Aims & Methods

MC is poorly understood and EGC role in MC is still unknown. Therefore, our aim is to investigate the involvement of EGC – due to their neuroimmune functions and involvement in intestinal dysmotility – in patients with MC. In addition, mast cells will be investigated since altered interactions with EGC have been demonstrated during IBS⁵.
Paraffin-embedded colonic biopsies from patients with active CC, LC, UC, IBS-diarrhea (D) and healthy controls (HC) were collected (n=13-26 per cohort). In addition, a subset of CC patients was also sampled during successful treatment with glucocorticosteroid 9mg budesonide (n=13). The amount of EGC was quantified using glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100β). Mast cells were quantified using tryptase.

Results

Immunofluorescence analysis of EGC revealed an increased amount of EGC^GFAP+ in CC compared to HC (p<0.001). Of note, CC EGC^GFAP+ levels were comparable to those shown by biopsies from patients suffering from IBS-D and UC. Among the 13 CC patients with paired samples before and under budesonide treatment, we observed a trend toward reduced EGC^GFAP+ levels during treatment (p = 0.08). In contrast, LC patients displayed similar EGC^GFAP+ levels as to HC, but lower than those observed in biopsies from patients with CC, IBS-D, and UC (p<0.001). On the other hand, EGC^S100β+ were increased only in active CC (p<0.0001). Yet, UC patients displayed the highest level of EGC^S100β+ (p<0.0001). Mast cells analysis showed an increased counts for tryptase in CC before and under treatment compared to HC (p<0.01).

Conclusion

Our findings indicate that EGC and mast cells are involved in CC pathogenesis due to an increased reactivity of EGC and mast cells in the colonic mucosa. CC patients exhibit signs of EGC^GFAP+ levels comparable to those observed in UC and IBS-D. Oppositely, LC seems to be independent of neuroinflammation as EGC and mast cells presence was comparable to HC. These preliminary findings support the theory that CC and LC are distinct disease entities. Future work will include RNA sequencing of EGC-related genes, counts of eosinophils as well as in situ analysis of mast cells and eosinophils degranulation, and assessment of budesonide effects on EGC in vitro.

References

1. Nyhlin N, Wickbom A, Montgomery SM, et al. Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study. Aliment Pharmacol Ther 2014; 39: 963-972. 20140311. DOI: 10.1111/apt.12685.
2. Carrasco A, Esteve M, Salas A, et al. Immunological Differences between Lymphocytic and Collagenous Colitis. J Crohns Colitis 2016; 10: 1055-1066. 20160229. DOI: 10.1093/ecco-jcc/jjw058.
3. Escudero-Hernandez C, Munch A, Ostvik AE, et al. The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis. J Crohns Colitis 2020; 14: 962-973. DOI: 10.1093/ecco-jcc/jjaa020.
4. Gonzales J and Gulbransen BD. The Physiology of Enteric Glia. Annu Rev Physiol 2024 20241115. DOI: 10.1146/annurev-physiol-022724-105016.
5. Meira de-Faria F, Casado-Bedmar M, Marten Lindqvist C, et al. Altered interaction between enteric glial cells and mast cells in the colon of women with irritable bowel syndrome. Neurogastroenterol Motil 2021; 33: e14130. 20210402. DOI: 10.1111/nmo.14130.

Introduction

Dysregulated activation of myeloid cells, including monocytes and macrophages, contributes to intestinal inflammation in Inflammatory Bowel Disease (IBD) through excessive release of pro-inflammatory cytokines. Microbial-derived short-chain fatty acids (SCFAs) modulate the inflammatory and metabolic nature of these cells through activation of a wide-range of cellular signalling pathways. Several of these pathways—including targeting Free-fatty acid receptors (FFA1, FFA2, FFA3) and other metabolic pathways (Glycolysis and Oxidative phosphorylation) have exhibited potential by influencing the polarisation from inflammatory to regulatory macrophages. In this study, we aim to unravel these mechanisms and explore the interplay between myeloid cells and SCFAs in IBD.

Aims & Methods

We first investigated the immunomodulatory effects of SCFA on THP-1 and monocyte-derived macrophage (MDM) models of inflammation. These cells were polarised toward an M1-like phenotype (LPS+ IFN-γ) in the presence of SCFAs or pharmacological agonist of FFA3 (AR420626). We analysed how these treatments impacted cytokine secretion and markers of polarisation using ELISA and RT-qPCR. To gain insight with a disease context, CD14+ monocytes from the peripheral blood of IBD patients (n=6), were exposed to M1 polarising stimuli (LPS+IFN-γ), in the presence of SCFAs or AR420626. To explore potential disease-specific responses, monocytes from actively inflamed IBD patients (n=7) and healthy controls (HC) (n=3) were cultured in presence of butyrate (1mM) in the absence of inflammatory stimulus. In both instances, RT-qPCR and ELISA were conducted to assess secretion of pro-inflammatory cytokines and activation of metabolic pathways.

Results

In THP-1 and MDM models, treatment with butyrate (4 mM) markedly suppressed IL-6 secretion, an effect that was mimicked by the FFA3 agonist AR420626 (50 µM). These responses extended to IBD patient-derived monocytes, where strong induction of IL-6 and TNF-α were repressed by both butyrate and propionate (vs M1; p< 0.001). FFA3, which plays an important role in mediating responses to SCFAs, was also upregulated in M1 polarised patient monocytes (vs Unt; p< 0.05). However, this elevated expression was abrogated in monocytes that were exposed to butyrate (1mM), giving insight toward how butyrate can regulate SCFA sensing mechanisms under inflammatory conditions. Interestingly, this pro-inflammatory monocyte phenotype was accompanied by raised expression of the glycolysis markers HK2 and GLUT1 —which, again, were repressed by butyrate (vs Unt; p< 0.05). In untreated monocytes derived from IBD patients, we observed an elevated inflammatory state relative to HCs, suggesting prior disease-associated activation. While these cells displayed heightened baseline expression of HK2 than HC monocytes, this was attenuated by exposure to butyrate (vs Unt; p< 0.05), and cells were rescued from this hyper-inflammatory phenotype.

Conclusion

Taken together, these results highlight that butyrate helps to counteract inflammation in IBD monocytes —possibly stemming from an influence on glycolysis. This work demonstrates that monocyte metabolic activity and SCFA-sensing pathways are dysregulated under inflammatory conditions. These findings provide new insight into the altered immune-metabolic state of monocytes in IBD and highlight the important role of microbial-derived SCFAs to restoring immunometabolic balance.