bluuebunny/crossref_metadata_2025 huggingface dataset:
P1288 The Association of Long-term Night Shift Work and Related Circulating Proteins with Inflammatory Bowel Disease: A Prospective Cohort and Multi-omics Study
Authors: Zhao J , Xue E , Yu G , Ye J , Li X
Published: January 2025

Background

The association between night shift work and the risk of inflammatory bowel disease (IBD) remains unclear. We aim to investigate the association between night shift work and the risk of IBD, ulcerative colitis (UC), and Crohn’s disease (CD), while further investigating the roles of genetic susceptibility and circulating proteins.

Methods

This cohort study included 149,014 UK Biobank participants without IBD at baseline, with 28,772 undergoing proteomic detection. Cox regression assessed associations between night shift work, circulating proteins, and IBD risk, while multinomial logistic regression identified proteins linked to night shift work. Bulk RNA-seq (1,030 blood, 453 intestinal tissue, and 176 Ustekinumab-treated intestinal samples) and single-cell transcriptomics (51 samples, 163,336 cells) were integrated to explore the roles of night shift-related proteins in IBD development and progression.

Results

During a mean follow-up of 13.66 years, 818 incident IBD (556 UC and 262 CD) cases were documented. Compared to day workers, there was a significant increasing trend in the frequency of current shift work and the risk of incident IBD (Ptrend=0.018). Among individuals with usual or permanent night shifts work, the risk of IBD incidence increased by 56% compared to those with no shift work, with a hazard ratio (HR) of 1.56 (95% CI: 1.15-2.13), especially for in those with intermediate genetic susceptibility to IBD. Additionally, there was a significant increasing trend in the frequency of current shift work and the risk of incident UC (Ptrend=0.037). High genetic risk individuals with usual or permanent night shifts work were respectively associated with a 3.60-fold increase in the risk of IBD, a 3.13-fold increase in the risk of CD, and a 2.77-fold increase in the risk of UC. Compared with shift workers never working nights, participants with an average frequency of more than 8 nights per month of night shift work exposure possessed higher IBD risk (HR 1.54, 95%Cl: 1.07-2.23). Six circulating proteins (IL18R1, GDNF, SOD1, TNFRSF6B, MMP12, and CCL7) related to night shift work were associated with the risk of incident IBD. Multi-omics evidence indicated that MMP12 increased UC risk through macrophage function and reduces the efficacy of Ustekinumab, while CCL7+ monocytes, possibly in conjunction with ACKR1, may facilitate the initiation of inflammation in CD.

Conclusion

Night shift work has been associated with an increased risk of IBD, CD, and UC, with MMP12 and CCL7 identified as potential drivers of this association. Further research is needed to assess whether reducing night shift frequency and duration, combined with targeted protein interventions, could mitigate IBD risk and improve prognosis.
P1291 Transcriptional heterogeneity of granzyme K CD8 T Cells in Crohn’s Disease: Implications for tissue inflammation
Authors: Lee Y , Baek J , Kim Y , Hwang S W , Lee J L , Park S H , Kim J , Yang S K , Han B , Kweon M N , Song K , Yoon Y S , Ye B D , Lee H S
Published: January 2025

Background

Crohn’s disease (CD) pathogenesis involves complex interactions between immune cells and intestinal tissues. We investigated the heterogeneity of CD8 effector T cells (Teff) and their role in CD inflammation at the single-cell level.

Methods

T cells were isolated from blood, inflamed, and uninflamed intestinal tissues of 15 patients with CD. Various combinations of single-cell RNA sequencing, TCR sequencing, and spatial transcriptomics were performed on subsets of these samples to comprehensively analyze the cellular landscape.

Results

Analysis of 41,699 CD8 T cells revealed two main CD8 Teff subsets: granzyme B (GZMB+) Teff cells, predominantly in blood with high cytotoxic potential, and granzyme K (GZMK+) Teff cells, enriched in intestinal tissue with lower cytotoxic potential. In the intestine, GZMK+ and GZMB+ Teff cells exhibited distinct transcriptional profiles. GZMB+ Teff cells showed higher expression of KLF2 and its target genes, including tissue egress markers S1PR1 and S1PR5, suggesting circulation propensity. In contrast, GZMK+ Teff cells displayed a tissue residency signature, with reduced egress-related gene expression and increased AP-1 transcription factors (FOS, FOSB, JUN). TCR clonotype analysis revealed substantial clonal expansion of GZMK+ Teff cells and high clonal overlap with CD8+ tissue-resident memory T (Trm) cells. Cell-cell communication analysis demonstrated GZMK+ Teff cell interactions with myeloid cells through the CXCR3/CXCL9,-10 axis, which was confirmed by spatial transcriptomics. Delving deeper into the heterogeneity of GZMK+ Teff cells, we identified three distinct subpopulations, each characterized by unique functional attributes: cytotoxic GZMK+ cells expressing high levels of PRF1, GNLY, and GZMB; stem-like GZMK+ cells expressing TCF7, a key regulator of T cell stemness; and Trm-like GZMK+ cells with high CXCR6 expression, indicative of long-term tissue residence. Notably, the Trm-like GZMK+ T cells displayed elevated levels of pro-inflammatory cytokines (IFNG, TNF), suggesting their potential role in tissue inflammation.

Conclusion

Our study reveals the transcriptional heterogeneity of CD8 Teff cells in blood and intestinal tissues of patients with CD. We identified intestinal GZMK+ CD8 Teff cells that may contribute to local inflammation through myeloid cell interactions. These findings provide new insights into CD pathogenesis and may guide the development of targeted therapies modulating tissue-specific immune responses.
P1293 Novel mutations in SASH3 cause very early onset IBD by impairing the NF-kB and mTORC1 pathways
Authors: Tang W , Piao L , Zhong H , Mao J , Jiang Z , Huang T , Huang Y
Published: January 2025

Background

Human SAM and SH3 domain-containing 3 (SASH3) variants globally affect TCR signaling including its downstream mTORC1 and NF-kB signaling. These 3 pathys play great roles in the pathogenesis of very early-onset inflammatory bowel diseases (VEO-IBD). Here, we report a now 4-year-old patient (P1) who was ultimately diagnosed with SASH3 deficiency in the nuclear localization signal 1(NLS1) of the protein presenting with VEO-IBD along with his adult uncle clinically asymptomatic (P2) who carries the identical variant.

Methods

a 3.2-year-old boy suspected VEO-IBD was evaluated in our clinic. Tissues were obtained by endoscopy. Genomic DNA, extracted from the peripheral blood mononuclear cells of the child and parents, were subjected to whole-exome sequencing(WES) and sanger sequencing. After mutations in the SASH3 were identified, sanger sequencing were performed for their relatives,the immunological features of our patients were analyzed including the cell proliferation assay by flow cytometry. Western blot(WB) was performed to study the protein level of SASH3 and the NF-kB and mTORC1 pathways in patients.

Results

P1 was diagnosed with Crohn’s disease according the images of endoscopy and biopsies (Figure A). WES and sanger sequencing identical a variant at exon1 in SASH3 (c.10 C>T/p.R4C ) in P1, his mother was a heterozygous carrier (Figure B). Sanger sequencing confirmed that P2 who was clinically asymptomatic to date, carries the identical variant at exon1 in SASH3 (c.10 C>T/p.R4C ) which inherited from P1’ grandmother(Figure C,D). The SASH3 variants identified in them is located in the NLS1 of the protein(Figure E), it caused the protein is exclusively located in the cytoplasm and no protein was found inside the nucleus which were proved by WB( Figure F). The immune phenotype were not seriously damaged in our 2 patients at homeostatic conditions, but upon stimulation with anti-CD3 and anti-CD28, both CD4+ and CD8+ T cells from P1, demonstrated impaired expression of CD71 and GLUT1 (FigureG, H), indicating defective cell proliferation and activation. The WB demonstrated that both the level of p-NFkB-p65 and p-S6 was markedly reduced in P1 (Figure I). We used Infliximab to treat P1, one year later the endoscopy showed mucosal healing and the pathology showed improved in inflammation and absent in granulation tissue. (Figure J)

Conclusion

We identified a novel mutations in SASH3 located in the NLS1 of the protein which cause VEO-IBD by impairing the NF-kB and mTORC1 pathways.
P1300 HLA-C*06 Genotype and Ustekinumab Therapy Persistence in Inflammatory Bowel Disease
Authors: Corcoran R , Ryan A , Doherty J , Quinn E , Conroy J , Conroy J , O’Hara F , Cullen G , Sheridan J , Bailey Y , Dunne C , Hartery K , McNamara D , Doherty G , Kevans D
Published: January 2025

Background

Ustekinumab (UST) is an anti-IL12/23 monoclonal antibody approved for use in psoriasis and inflammatory bowel disease (IBD). HLA-C*06 allele carriage has been associated with higher rates of response to UST in psoriasis patient populations.1 The association between HLA-C*06 carriage and UST response in IBD has not been previously evaluated.

We aimed to further explore HLA-C*06 carriage as a pharmacogenetic marker as a response to UST therapy in IBD patients.

Methods

A multi-centre retrospective study of IBD patients treated with UST in Ireland was performed. Baseline demographics of the cohort were collected. HLA-C*06 genotypes were generated by imputation from whole genome sequence using HIBAG. UST therapy persistence, was considered a proxy for treatment response, and was expressed as time to discontinuation of UST therapy. The primary endpoint was UST therapy persistence segregated by HLA-C*06 allele genotype. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR).

Results

143 IBD patients were identified and included in the study population. In this population, 32 patients (22%) carried at least one HLA-C*06 allele. There was no significant difference in median time to UST therapy discontinuation comparing HLA-C*06 carriers to non-carriers at 700-days follow-up, p=0.32 [Figure 1]. In a multivariate regression neither HLA-C*06 allele carriage (OR 1.2, p=0.5), male gender (OR 1.2, p=0.6), CD phenotype (OR 1.6, p=0.44), nor concomitant immunomodulator use (OR 1.1, p=0.8) were independently associated with time to UST therapy discontinuation.

Conclusion

HLA-C*06 allele carriage is not associated with increased UST therapy persistence in IBD. Larger studies of UST therapy outcome in IBD patients with characterised HLA-C*06 genotype are required to confirm this finding.

References

1.Talamonti M, Galluzzo M, Chimenti S, Costanzo A. HLA-C*06 and response to ustekinumab in Caucasian patients with psoriasis: Outcome and long-term follow-up. J Am Acad Dermatol. 2016;74(2):374-5.
P1301 Bile acid composition and immunological effect in mouse model and IBD patients
Authors: Leistl S , Hu K , Rauh M , Neurath M , Günther C
Published: January 2025

Background

Bile acids (BAs) were suggested to have immunomodulatory properties that could influence inflammatory pathways in Inflammatory Bowel Disease (IBD). Dysregulated BA metabolism has been observed in IBD patients, further presented in our study by an analysis of IBD patients BA profiles with association to gene expression and targeted treatment of organoid models to elucidate the specific mechanisms by which BAs may affect intestinal inflammation in IBD.

Methods

Small intestinal organoids were grown from WT mice and an IBD mouse model with caspase-8 KO in intestinal epithelial cells (IEC). Organoids treated with primary (1°) and secondary (2°) BAs (CDCA, LCA, DCA) and BA + JAK-inhibitor (CDCA + inhibitor) were analysed thoroughly by bulk-RNA sequencing to investigate effects of BA and possible strategies to ameliorate negative effects.

BA composition of serum samples from healthy controls (HC) (n=25) and IBD patients (n= 85) was quantified using LC-MS/MS and compared to bulk-RNA sequencing results of the same individuals in order to identify correlations of BA abundancy and gene expression.

Results

In WT organoids, CDCA treatment induced a significant upregulation of numerous genes associated with key cellular processes such as immunological, cell death but also mitochondrial. In contrast, in genetically-predisposed IBD organoids predominantly displayed gene downregulation in response to CDCA, indicating a divergent transcriptional response between WT and KO genotypes. In IBD organoids, JAK inhibition in conjunction with CDCA significantly altered the expression profile, reversing the expression of several genes that were downregulated by CDCA alone. This reversal was gene-specific and suggests a compensatory or modulatory effect of JAK inhibition on CDCA signalling in a caspase-8 deficient background. Notably, this combinatorial effect was not observed in WT organoids, where CDCA + JAK inhibitor treatment did not substantially alter gene expression compared to CDCA alone.

Targeted metabolomic analysis of patient serum samples revealed two distinct bile acid profiles within the IBD cohort. In one subgroup, serum was characterized by elevated levels of the 1°BA CDCA coupled with lower concentrations of both primary and conjugated 2°BAs. In contrast, a second subgroup displayed lower CDCA levels alongside increased concentrations of secondary bile acids. These bile acid composition patterns suggest differing metabolic states within the patient cohort.

Conclusion

Our findings reveal significant links between BA composition, gene expression, and JAK pathway modulation, offering new insights into BA–driven gene regulatory mechanisms in both murine organoids and an IBD patient cohort.

References

TRR241 IBDome Consortium, TRR 241 Research Initiative, Berlin-Erlangen, Germany
P1302 OCTN1 variants shape innate immunity and predict individual response to vedolizumab in ulcerative colitis patients: from preclinical models to AI
Authors: Puca P , Capobianco I , Masi L , Petito V , Poscia A , Coppola G , Schiavoni E , Napolitano D , Del Chierico F , Palucci I , Laterza L , Pugliese D , Lopetuso L , Putignani L , Gasbarrini A , Giovanni P , Scaldaferri F
Published: January 2025

Background

Limited evidence is available about predictors of response to specific medications for ulcerative colitis. Variants of OCTN1, an organic cation transporter, could modulate the inflammatory response and potentially predict individual response to immune-modulatory therapy.

Methods

We first assessed the ability of OCTN1 to differentially modulate IL1β secretion under different stimuli in a human leukemia monocytic cell line (THP-1) and in human peripheral blood mononuclear cells. We therefore prospectively enrolled a cohort of UC patients starting either anti-TNFα or vedolizumab, determined their OCTN1 genotype and evaluated their response to therapy after six months, as well as steroid free therapy persistence after 2 years. Finally, we performed an integrated machine learning based analysis including serum cytokines and gut microbiota analysis.

Results

OCTN1-deficient THP1 cells showed reduced IL-1β secretion in response to peptidoglycan (PGN) and Fusobacterium nucleatum (Fn), whilst primary monocytes bearing OCTN1 503F variant displayed an increased production of IL-1β in response to PGN and live bacteria. We therefore enrolled 90 patients, of which 50 starting anti-TNFα and 40 vedolizumab. At the multivariate analysis, a significant reduction of clinical response after six months was observed in patients with 503F variant treated with vedolizumab. The same trend was observed for steroid free therapy persistence after two years. The machine learning analysis revealed that changes in bacterial composition, notably the relative abundance of Gemellaceae, followed by Lachnospiracea, were significant predictors of lack of two-year steroid-free therapy persistence.

Conclusion

Mutated OCNT1 genotype (503F) could favor an increased IL1β secretion from human leukocytes, thus suggesting a worse disease course and lower response to vedolizumab as compared to 503L. ovel machine learning data analysis provides further insights into such topic.
P1309 Is there any association between genetic polymorphisms and response to Anti-TNFs in patients with inflammatory bowel disease ? Experience of a Tunisian IBD center
Authors: Harrathi S , Hammami A , Idriss N , Medhioub M , Jaziri H , Dahmeni W , Braham A , Ajmi S , Ben Slema A , Hamzaoui L , Ben Hadj Slema F , Elleuch N , Ksiaa M
Published: January 2025

Background

Although highly effective, primary failure and loss of response to anti tumor necrosis factors (anti-TNF) alpha in inflammatory bowel disease (IBD) are common and associated with poor clinical outcomes. Multiple factors, including genetics, have been involved in the response to anti TNF alpha therapy. Thus, the purpose of our study was to evaluate the impact of the polymorphism of the SNPs rs1799724 (TNF alpha), rs767455 (TNFRSF1A), and rs1061622 (TNFRSF1B) in the response to anti-TNF alpha treatment in Tunisian IBD patients.

Methods

We conducted a prospective study including patients followed for IBD and treated with anti-TNF alpha. We classified these patients into two groups: responders and non-responders to anti-TNF alpha.

Genomic DNA was purified from peripheral blood leucocytes using the salting-out method. Subjects were genotyped for polymorphisms TNF (rs 1799724), TNFRSF1A (rs767455) and TNFRSF1B (rs1061622) using a variant of allele-specific PCR, Mutagenically Separated PCR (MS-PCR). Genotypic and allelic frequencies were compared between the two groups of patients.

Results

We included 61 IBD patients with a mean age of 38,9 years [18-64 years]. Forty six patients (75.4%) had CD and 15 (24.6%) had UC. In the CD group, 35 (76.1%) patients were treated with infliximab and 11(23.9%) with Adalimumab. Nineteen were responders to treatment (41,3%) and 27 (58.7%) experienced treatment failure: primary failure in 4 and loss of response in 23.

Genetic analysis did not show any association between the response to anti TNF alpha treatment and SNPs rs1799724 (TNF alpha) (P= 0,12 ; OR = 1,9) and rs1061622 (TNFRSF1B) (P= 0,9; OR= 1,06). Although, the CT genotype of rs767455 (TNFRSF1A) was associated with non-response (OR= 3.5 with a 95% CI [0.98-12.4], p=0.049).

In the UC group, 14 patients were treated with Infliximab and only one patient treated with Adalimumab. Seven patients responded to anti-TNF therapy (46.7%) and 8 were non-responders (53.3%) with 5 cases of primary failure and 3 cases of loss of response. We didn’t find any association between the SNPs rs1799724 (TNF alpha), rs767455 (TNFRSF1A), and rs1061622 (TNFRSF1B) and response to anti TNF alpha in the UC patients.

Conclusion

Among the three SNPs studied, only the rs767455 (TNFRSF1A) was shown to be associated with non-response to anti-TNF in chrohn’s disease patients. However, our results need to be validated in a larger sample of patients.
P1310 Role of gut pathobiont-derived membrane vesicles for biliary epithelium in PSC-IBD
Authors: Schwendner R , Stolzer I , Mattner J , Leistl S , Hensel I , Schloderer J , Böllet A , Schaufler K , Tripal P , Neurath M F , Günther C
Published: January 2025

Background

Primary sclerosing cholangitis (PSC), a cholestatic liver disease highly associated with inflammatory bowel disease (IBD), is characterized by progressive inflammatory destruction of bile ducts. Bacterial membrane vesicles (bEVs) derived from gut pathobionts may play a significant role in the pathogenesis of PSC-IBD by disrupting the biliary barrier, promoting liver inflammation and contributing to liver fibrosis. A deeper understanding of how bEVs influence bile duct homeostasis is crucial for unraveling the mechanisms behind PSC-IBD and developing targeted therapeutic strategies.

Methods

Bile duct organoids were generated from WT mice and PSC-IBD patients. BEVs were isolated from commensals or PSC-associated gut pathobionts following MISEV guidelines. To assess the role of bEVs to ductal barrier dysfunction and inflammation, we employed an organoid based permeability assay, immunofluorescence staining, qPCR and bulk RNA sequencing. Furthermore, to investigate whether the presence and amount of bEVs in the systemic circulation were associated with PSC-IBD, we analyzed serum-derived EVs from either healthy control, as well as PSC and PSC-IBD patients using Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and a TLR4-Receptor based reporter assay.

Results

Our results demonstrate that particularly bEVs isolated from gut pathobionts trigger signaling pathways associated with inflammation in both murine and human biliary epithelial cells. Furthermore, we observed a disease and strain specific fingerprint after bEV treatment, which was characterized by several significantly enriched terms related to PSC-related inflammation, including genes involved in T-helper 17 cell differentiation, and tumor necrosis factor (TNF) signaling. However, we did not observe a direct impact of bEVs on biliary barrier function. Consistent with this, we detected increased levels of bEVs in the systemic circulation of PSC-IBD patients, but not in those with PSC alone or in healthy controls, suggesting that these bacterial components may translocate across a compromised intestinal barrier into the bloodstream.

Conclusion

Overall, our study suggests that bEVs may contribute to biliary inflammation, but not barrier dysfunction and thereby may represent a novel player in the pathogenesis of PSC-IBD. Additionally, it underscores the critical role of bEVs in host-microbe communication, suggesting their potential as diagnostic biomarkers and highlighting, that therapeutic strategies targeting bEVs could offer promising avenues for managing PSC-IBD.
P1312 Clickable nanozyme enhances colonization of Saccharomyces boulardii by spatiotemporal guidance for ameliorating inflammatory bowel disease
Authors: Fang D , Wang L , Huang Y
Published: January 2025

Background

Compelling evidence indicates that dysregulated in the gut microbiota significantly contribute to the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions aimed at modulating the microbiota offer potential alternative approaches for treating IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability.

Methods

Here, we developed azido (N3)-modified Prussian blue nanozyme (PB@N3) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, IVIS and Photoacoustic imaging demonstrated clickable PB@N3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing click chemistry “N3-DBCO” to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Saccharomyces boulardii (S.Br@DBCO). The therapeutic effects of PB@N3 + S.Br@DBCO were verified by using the dextran sulfate sodium (DSS)-induced colitis mice model. Weight loss, fecal conditions, colon length and histopathological changes were monitored.

Results

PB@N3 targets and anchors to inflamed region. The "click" reaction between PB@N3 and S.Br@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, "click" reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N3 and S.Br@DBCO effectively enhances the colonization of probiotics, restores intestinal barrier function, and alleviates intestinal inflammation.

Conclusion

This is the first time that “click” chemistry was employed to combine fungal probiotics and nanozyme. PB@N3 spatio-temporal guidance enhances targeted colonization of S.Br@DBCO provides a promising medical treatment strategy for IBD.
P1316 Increased ultra-processed food consumption is associated with inflammation-promoting shift of gut microbiota in Inflammatory Bowel Disease
Authors: Kim K A , Im H W , Choi S , Shon W J , Kim J S , Kim B G , Im J P , Kim S H , Kim J W , Kang H W , Kim K W , Kim E S , Koh S J
Published: January 2025

Background

Previous epidemiologic studies have suggested that increased consumption of ultra-processed food (UPF) can increase the risk of developing inflammatory bowel disease (IBD) by exacerbating gut dysbiosis.1 However, studies directly linking UPF to specific microbial shift in IBD patients are limited. Our study explored differences in gut microbiota profile based on UPF intake in patients with IBD.

Methods

This multi-centre cohort study included 313 IBD patients from three hospitals. Patients were divided into four quartiles (Q1, Q2, Q3, Q4) based on their percentage UPF consumption, evaluated from the Korea National Health and Nutritional Examination Survey. 16S rRNA sequencing was conducted on stool samples to analyse microbial composition. Subgroup analysis was performed based on IBD activity, whereby faecal calprotectin 250 ug/g was used as a cutoff value for defining active and remission state. UPF quartiles were grouped as Q1, Q2 and Q3, Q4 when conducting subgroup analysis to maintain an adequate number of samples for comparison. Age-adjusted analysis was conducted on patients younger than 50 years.

Results

General characteristics of the study population showed that there were no significant differences in inflammatory markers between quartiles. However, age was significantly different (p=0.001), with the first quartile having the highest median age of 49 years. Microbial analysis showed differences in beta diversity across quartiles (p=0.046), with the abundance of Lachnospiraceae and Faecalibacterium decreasing as UPF consumption increased. Subgroup analysis showed that patients with active inflammation showed no difference in alpha or beta-diversity, but Lactobacillus was more abundant in Q1, Q2 than Q3, Q4. Patients in remission differed in beta-diversity (p=0.012), with a greater abundance of Lachnospiraceae and Faecalibacterium in Q1, Q2 and Escherichia/Shigella and Veillonella in Q3, Q4. Age-adjusted analysis showed that in active IBD, Lactobacillus was more abundant in Q1, Q2 whereas Enterobacteriaceae was more abundant in Q3, Q4. Age-adjusted analysis of patients in remission showed that Lachnospiraeae, Faecalibacterium, Bifidobacterium were more abundant in Q1, Q2 than Q3, Q4.

Conclusion

This study suggests that increased UPF consumption is associated with an inflammatory-promoting shift in the gut microbiome of IBD patients. Restricting UPF intake may be important for controlling gut inflammation and preventing IBD relapse.

References

1.Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol. Jun 2024;21(6):406-427. doi:10.1038/s41575-024-00893-5
P1326 Fecal Microbiota Transplantation for Refractory and Recurrent Clostridium innocuum Infection in Inflammatory Bowel Disease: A Pilot Study on Safety, Clinical Outcomes, and Microbiota Changes
Authors: Chiu C H , Le P H , Yeh Y M , Chiu C T
Published: January 2025

Background

Clostridium innocuum has emerged as a pathobiome with vancomycin resistance, posing challenges in inflammatory bowel disease (IBD) management. In ulcerative colitis (UC) patients, C. innocuum is associated with reduced clinical remission rates, while in Crohn’s disease (CD) it correlates with creeping fat and intestinal stricture formation1,2. Some IBD patients experience refractory or recurrent C. innocuum infections, even after metronidazole treatment1. This study aimed to evaluate the safety and feasibility of fecal microbiota transplantation (FMT) for treating refractory or recurrent C. innocuum infections in IBD.

Methods

In this pilot study, seven IBD patients (3 CD, 4 UC) with refractory (n=5) or recurrent (n=2) C. innocuum infection post-metronidazole treatment were enrolled. Patients received FMT and were followed up for six months. Clinical efficacy was assessed using the Crohn’s Disease Activity Index and Mayo Score. Microbiota changes were analyzed through alpha diversity measures and Bray-Curtis dissimilarity metrics.

Results

No adverse events occurred in any of the seven participants. All participants demonstrated clinical improvement following FMT. However, a mild increase in symptom severity was observed at the six-month follow-up. Persistent C. innocuum infection was noted in one patient, with an asymptomatic recurrence in another three months post-FMT. Microbiome analysis showed increased alpha diversity post-FMT, and Bray-Curtis metrics (Figure 1) indicated donor-like microbiota composition.

Conclusion

FMT appears to be a safe and feasible option for IBD patients with refractory or recurrent C. innocuum infections. Further studies with larger cohorts are necessary to validate these findings and assess long-term efficacy.

References

1.Le PH, Chiu CT, Yeh PJ, Pan YB, Chiu CH. Clostridium innocuum infection in hospitalised patients with inflammatory bowel disease. J Infect. 2022;84(3):337‒42. https://doi.org/10.1016/j.jinf.2021.12.031

2.Ha CWY, Martin A, Sepich-Poore GD, Shi B, Wang Y, Gouin K, et al. Translocation of viable gut microbiota to mesenteric adipose drives formation of creeping fat in humans. Cell. 2020;183(3):666‒83.
P1327 Microbial signatures associated with Inflammatory Bowel Disease in Australia: baseline data from the Australian IBD Microbiome study
Authors: Jayawardana T , Little R D , Zhang F , Koentgen S , Wu N , Tavakoli P , Sidhu S , Le A , Boussioutas A , Ward M G , Miles P S , Gibson P R , Ghaly S , Corte C , Talley N J , Leach S , Lemberg D , Dutt S , Paramsothy S , Leong R , Connor S J , Hold G ,   Australia IBD Microbiome (AIM) Study
Published: January 2025

Background

Microbial dysbiosis is associated with Crohn’s disease (CD) and ulcerative colitis (UC) onset and disease activity, however, large-scale data pertaining to Australian patients are limited1. This study aimed to describe the differences in gut microbiota composition between patients with IBD and healthy controls within the Australian IBD Microbiome (AIM) study2.

Methods

Paired faecal and oral samples alongside participant demographics and disease characteristics were collected at baseline from all healthy controls (HC) and IBD patients enrolled in the Australian IBD Microbiome (AIM) study from June 2019 to November 2023. Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R.

Results

751 participants (305 HC, 232 CD, 214 UC) returned baseline faecal (n = 697) and/or oral samples (n = 737) and were included in the analysis, with patient group characteristics presented in Table 1. Most IBD patients were in clinical remission (Table 1). However, CD and UC patients had comparably lower faecal alpha diversity than the HC group (Figure 1A). Faecal beta diversity differed between CD, UC, and HC groups (Figure 1B). Five phyla were significantly different between the three groups in faecal samples (Figure 1C). No significant inter-group differences were seen with oral microbial analysis.

Conclusion

Compared to healthy adults, patients with IBD in Australia have distinct gut microbial profiles. Faecal rather than oral microbial sampling demonstrated a difference in community structure between IBD and healthy groups. Incorporating longitudinal microbial sampling and increasing sequencing resolution may elucidate a pathogenic relationship between gut microbiota and IBD.

References

1.Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006

2.Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493
P1328 Reduced salivary alpha-diversity in Inflammatory Bowel Disease: Systematic review and meta-analysis of 1000 IBD patients – a role for oral microbiome as a marker of downstream dysbiosis in IBD
Authors: Wands D , Whelan R , Hansen R , Rimmer P , Iqbal T , Ho G T
Published: January 2025

Background

The gut microbiome is involved in the pathogenesis of CD, but the extent to which the oral microbiome contributes to this—and how it can be utilised for disease monitoring and therapeutics—remains under-explored. We aimed to characterise compositional differences in the oral microbiome of patients with IBD by conducting a systematic review and meta-analysis of the literature.

Methods

Medline, Embase, Web of Science, Cochrane, and SCOPUS were searched for articles published from inception to 1st February 2024. Primary screening and extraction were performed in duplicate. The extracted dataset included: disease phenotype, sampling data, diversity metrics, relative abundance analysis and sequencing/metadata availability. Random effects meta-analysis of the standardised mean difference of Shannon diversity was performed for IBD sub-types and disease activity.

Results

The initial search identified 1367 after removing duplicates; 37 studies were selected for full-text review, with 22 meeting the inclusion criteria. (Figure 1) Alpha diversity was reported in 20/22 (91%) of studies. Comparing salivary Shannon diversity of 976 undifferentiated IBD patients with 566 controls shows a significant reduction in patients with IBD (standardised mean difference [95% CI]: -0.29 [-0.54, -0.05]). In patients with high disease activity, there was a significant reduction in salivary Shannon diversity (IBD n = 133, control n = 181) (standardised mean difference [95% CI]: -0.51 [-0.98, -0.04]), which is lost when low activity patients are examined (IBD n = 128, control n = 170) (standardised mean difference [95% CI]: -0.12 [-0.46, 0.22]). (Figure 2) When examining beta diversity, significant dissimilarity in community composition between patients with IBD and controls was reported in 15/20 (75%) of studies. Relative abundance data of oral sites at a genus level was reported in 11/22 (50%) of studies. Changes are most frequently reported in the dominant phyla of the oral cavity (Bacillota, Bacteroidota, Actinobacter, and Pseudomonadota). The most frequently increased genera in IBD patients were Prevotella (4/11, 36%), Veilonella (3/11, 27%), Atopobium (3/11, 27%), and Megasphaera (3/11, 27%).

Conclusion

Based on this systematic review, there is evidence of distinct alterations in the oral microbiome composition of patients with IBD compared to controls which underscores the role of the oral microbiome as a potential indicator of downstream dysbiosis and crucial early immune-crosstalk in the oral cavity.
P1337 High fat diet drives increased dysbiosis in IBD compared to healthy controls
Authors: Koentgen S , Zhang F , Khadka S , O'Brien C , Grimm M , Allen-Vercoe E , Hold G L
Published: January 2025

Background

High fat diets (HFD), consisting of low fibre intake and high fat are associated with increased IBD risk. Industrialised diets have known impacts on host health but also impact the gut microbiota1; known to be altered in IBD. Whilst fat is primarily digested in the upper GI tract excess fat travels to the colon, the hub of microbial activity. In this study, microbial community changes in response to HFD were compared in a healthy and IBD patient donor using in vitro continuous culture chemostats.

Methods

Stool from a healthy donor and a de novo, treatment naive IBD patient were used to seed independent bioreactors. Standard diet was fed until microbial stabilisation followed by 14 days of HFD. Standard diet was then resumed for a 14-day recovery period. Daily sampling was used to assess changes in microbial composition (16S rRNA amplicon sequencing) and function (short chain fatty acids (SCFA) measured by gas-chromatography mass spectrometry).

Results

Despite comparable bacterial densities at stability the IBD vessel had higher total SCFA output compared to healthy. SCFA profiles were unique between donors with higher acetate and propionate concentration in the IBD vessel (p<0.0086). Butyrate at stability, however, was higher in the healthy vessel (p=0.025). HFD resulted in a depletion of acetate and propionate in both donors and an increase in isobutyrate, isovalerate, heptanoate and octanoate. Following transfer back to standard diet, the healthy vessel remained depleted of propionate (p= 0.0009) and butyrate remained significantly depleted in the IBD vessel (p= 0.0034) and did not recover (stable: recovery; p<0.0001).

Healthy only: HFD significantly lowered microbial (alpha) diversity by observed and Shannon metrics (p<0.034) but was unchanged in Chao1 index. By recovery alpha diversity realigned with the stable phase. Beta diversity showed unique composition across each experimental phase (p<0.02). HFD saw a depletion of Faecalibacterium and Blautia in favour of Escherichia-Shigella and Parasutterella genera. Sequence analysis of the IBD vessel is underway.

Conclusion

HFD affected both HC and IBD microbial communities; isovalerate and isobutyrate levels increased indicating greater amino acid (protein) metabolism by community members. Higher levels of heptanoate and octanoate are indicative of increased fatty acid degradation. The healthy donor had a more robust recovery with only 5 SCFAs remaining altered. In comparison, 8 metabolites remaining altered in IBD with a dramatic impact on butyrate production highlighting the greater fragility in the IBD microbiome. The findings support the need for further mechanistic understanding of the role of diet and microbial changes in IBD.

References

1.Agans R, Gordon AH, Kramer DL, Pérez-Burillo S, Rufián-Henares JÁ, Paliy O. Dietary Fatty Acids Sustain the Growth of the Human Gut Microbiota. Applied and Environmental Microbiology. 2018;84(21). doi:10.1128/aem.01525-18
P1355 Analysis of fecal bacterial and viral characteristics in patients with ulcerative colitis based on metagenomic sequencing
Authors: Shen X , zhang X
Published: January 2025

Background

Ulcerative colitis (UC) is an inflammatory disease mainly characterized by intestinal lesions, with persistent or recurrent diarrhea, mucous purulent stools as the main symptoms, accompanied by abdominal pain, urgency, and various systemic symptoms. The coexistence of viral bodies and other components of the microbiota with the host, in a dynamic equilibrium state, is a key factor in maintaining intestinal homeostasis and function[1].

Methods

Perform metagenomic sequencing on the feces of 52 UC patients and 15 normal individuals to analyze the abundance of gut microbiota and viruses and their correlation with clinical indicators.

Results

1. UC patients have dysbiosis of the gut microbiota, with a significant decrease in Bacteroidetes and a significant increase in Actinobacteria and Pseudomonas. There was a significant difference (q<0.05) in the presence of intestinal Rosebery bacteria between the healthy control group and the severe UC group; There were significant differences (q<0.01) between the healthy control group and the UC severe group in terms of Streptococcus lactis, Enterococcus faecium, Escherichia coli, Plantarum lactis, Lactobacillus rectalis, Enterococcus faecalis, and Lactobacillus reuteri. 2. UC patients have intestinal viral dysbiosis, There were statistically significant differences (q<0.05) between healthy individuals and patients with severe UC in terms of Bacteriophage sp., Enterococcus phage plant, Porcine type-c oncovirus, Lactobacillus phage LfeSau, and Siphaviridae sp. ctsfh5; There is a statistical difference (q<0.05) between mild and severe UC patients in Siphaviridae sp. ct4aE30, Enterococcus phage plantet, Siphaviridae sp. ctqOv4, Lactobacillus phage LfeSau, and Siphaviridae sp. ctsfh5. 3. We conducted a correlation study between differential microbiota and viruses and clinical indicators, and found that intestinal Roseburi bacteria were negatively correlated with modified Mayo score, ESR, and hsCRP; It is positively correlated with HGB. Siphaviridae sp. ctPB44 is negatively correlated with the modified Mayo score, ESR, and hsCRP. 4. We observed significant changes in the functional composition of the fecal microbiome in UC, with several microbial genes and functions identified in severe UC being more abundant than those in healthy individuals, including K13140, K01223, K02761, and K09454.

Conclusion

The gut microbiota and viruses of UC patients are disrupted, and whether in healthy individuals or UC patients, the predominant gut virus is Caudovicetes sp. However, the abundance of Caudovicetes sp. increases in UC patients. There is a certain correlation between intestinal Roseburia bacteria, Siphaviridae sp. ctPB44, and clinical indicators such as ESR, hsCRP, and HGB.

References

[1] Tun HM, Peng Y, Massimino L, et al. Gut virome in inflammatory bowel disease and beyond. Gut. 2024 Jan 5;73(2): 350-360.
N10 “I probably am being a naughty boy, but…” Exploring reasons for non-adherence to prescribed medication, as perceived by people living with Inflammatory Bowel Disease: A Qualitative Study
Authors: King K , Norton C , Chalder T , Czuber-Dochan W
Published: January 2025

Background

Inflammatory bowel disease (IBD) is treated with medications to induce and maintain remission. However, many people with IBD do not take treatments as prescribed. Identifying and understanding reasons behind medication adherence and non-adherence in IBD is critical.

Methods

In-depth, semi-structured interviews were audio or video-recorded and transcribed verbatim. Braun and Clarke’s (Braun & Clarke, 2006) principles of thematic data analysis were followed to analyse data.

Results

Twenty people living with IBD were purposively selected and interviewed. Four main themes were identified (Table1) with related sub-themes; 1) The Context within which adherence needs to happen 2) Battles throughout the IBD “journey” 3) Multiple medical treatment issues and 4) Knowledge, learning, understanding and experience of IBD as a condition and its treatment.

From diagnosis and throughout their IBD “journey,” medication adherence in many participants was variable. Adherence was impacted by the context of healthcare received by individuals, their daily activities, physical and emotional well-being and relationships with others. Participants regularly described themselves as experiencing a battle using intense terms such as battling with their IBD, their healthcare professionals (HCPs) and/or their IBD medication. Treatment type (including drug category, for example steroids or immunosuppressants, associated risks and side effects), treatment effectiveness and requirements for taking it, all influenced adherence, as did an individual’s treatment values and beliefs. Gaining knowledge, developing understanding regarding medication and its necessity from the start of diagnosis was critical for adherence. This had strong potential to impact adherence positively and/or negatively, based upon what participants were told, when, and by whom. Yet, treatment information was frequently not offered by HCPs, leading individuals to self-educate and develop a personal understanding of their condition and medication. This, combined with the experiencing of living with IBD, influenced their adherence.

Conclusion

Medication adherence is a journey, affected by multiple determinants. Determinants may be patient-centred, influenced by HCPs and/or determined by an individual’s knowledge and experience level. Diagnosis is a critical stage where individuals require compassionate care from their personal networks and multidisciplinary HCPs. Clear medical treatment information should also be provided by HCPs, with self-education encouraged via trusted resources. To promote adherence and establish treatment routines, patients must feel fully informed, supported, confident and comfortable in their shared decision-making about treatment, that will suit their lifestyle.

References

-Braun, V. & Clarke, V. (2006). Using thematic analysis in psychology. Qualitative Research in Psychology, 3 (2), 77-101
N21 Clinical Nurse Specialist in Inflammatory Bowel Disease (CNS-IBD). Care challenges and economic sustainability. A Scoping review
Authors: Mozos Muñoz C , Lavín Expósito C , Bouhmidi Assa Kali A , Jurado Monroy R M , Pinilla Sánchez J , Bonillo Merino C
Published: January 2025

Background

Inflammatory Bowel Diseases (IBD), as part of an immune-mediated chronic illness with a tendency for symptom exacerbation that can be difficult to predict, have a significant impact on the patient's quality of life, greatly diminishing their overall well-being.

The healthcare demand of patients and the need to continue improving health-related quality of life (HRQoL) while reducing healthcare expenditure create the necessity for the role of the Clinical Nurse Specialist in Inflammatory Bowel Disease (CNS-IBD) to achieve therapeutic success.

Therefore, the main objectives of our research are to assess the relationship between consultations with the Clinical Nurse Specialist in Inflammatory Bowel Disease and the patient's health-related quality of life, and, secondarily, to evaluate the economic sustainability of this consultation within healthcare systems.

Methods

Searches were conducted in the following databases: PubMed, UpToDate, Cochrane Library, Scopus, and CINAHL, as well as in relevant scientific journals: BMJ Open and The New England Journal of Medicine (NEJM).

There were no time or language restrictions. A total of n = 6,620 articles were retrieved. After applying eligibility criteria, n = 257 articles were deemed potentially relevant for abstract review. N = 117 articles were reviewed in full. Finally, n = 5 studies published between 2012 and 2022 were included.

Results

The results show an improvement in health-related quality of life, as measured by the IBDQ-32 and the PRO measures questionnaire, thanks to greater patient empowerment and better disease management. The reduction in hospital admissions and the prompt response to flare-ups indicate a decrease in healthcare costs and the burden on healthcare facilities.

Conclusion

This scoping review summarises the current scientific evidence regarding the effectiveness of the Clinical Nurse Specialist in Inflammatory Bowel Disease and its impact on improving the health-related quality of life of patients, as well as the efficiency and sustainability it can offer to healthcare institutions. The evidence in this scoping review suggests that CNS-IBDs play a key role in patient care and the improvement of HRQoL. However, medical follow-up and treatment remain essential for better control of clinical symptoms. Studies addressing the economic efficiency of this intervention within our research yielded significantly positive results. Nevertheless, the scientific evidence is limited, with a clear shortage of studies specifically focusing on nursing practice to improve the life conditions of patients.