bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.