bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1311 Mucosal Microbiome Signatures Associated with Postoperative Endoscopic Recurrence in Paediatric Crohn’s Disease
Authors: Breton MDCM- MSTR J , Tanes C , Wilson N , Kachelries K , Bittinger K , Mattei P , Baldassano R 
Published: January 2025

Abstract

Background
Following ileocecal resection (ICR) for Crohn’s disease (CD), recurrence is frequent even in the biologic era. Gut microbiota is involved in this setting and a few adult studies have suggested that bacterial recolonization after surgery may predict recurrence. Given the inherent risk of postoperative recurrence associated with age and disease duration, studies investigating the role of the gut microbiota in predicting relapse in children undergoing ICR appears critical. We aimed to identify changes in the mucosal microbiome associated with, and predictive of, endoscopic CD recurrence within the first year post-ICR in a paediatric population.

Methods
Microbiota composition (16S rDNA sequencing) was assessed from ileal and colonic mucosa at the time of ICR and later during endoscopic evaluation from above and below the surgical anastomosis in 33 patients (26 with paired samples) prospectively recruited at a tertiary care paediatric IBD center.

Results
The study included 33 children (mean age 16±2.7 years) undergoing ICR. At the time of ileo-colonoscopy, 9 (35%) patients had endoscopic recurrence (Rutgeerts’ score≥ i2). ICR strongly modified the gut mucosal microbiota composition with significant changes in β-diversity (R2= 0.03, PERMANOVA test, p=0.01). Bacterial recolonization post-ICR differed according to recurrence status (Figure 1). Post-operatively, recurrence was associated with an increase in Fusobacterium, Dialister genera and in members of the Lachnospiraceae family, and a decrease in Faecalibacterium, Lactobacillus genera and members of the Streptococcaceae family. Microbiota colonizing the neoterminal ileum and subanastomotic colon differed in children with recurrence and showed, compared to remission, elevated and reduced bacterial abundance of the Enterobacter (q=0.1) and Ruminococcaceae (q=0.05) families in colonic samples respectively while the ileal mucosa exhibited profound depletion in Faecalibacterium (q=0.01). Postoperative colonic mucosal relative abundance of Enterobacteriaceae (q=0.06) and Ruminococcaceae (q=0.06) correlated positively and negatively with length of intestinal resection. At the time of surgery, several bacterial taxa able to predict relapse were identified (Figure 2).

Conclusion
Predicting postoperative CD relapse remains challenging, although several clinical risk factors of recurrence have been identified. Our study demonstrates that bacterial recolonization following ICR might pave the way towards remission or recurrence. Our results highlight, for the first time in a paediatric population, target species that may help clinicians to better define patients at risk of relapse and allow precise modulations of the overall microbial ecosystem towards remission pattern.
P1315 Decoding microbiome-metabolome interactions: gaining insights into Gastric Cancer, Inflammatory Bowel Disease and Colon Cancer
Authors: Philip D , Hodgkiss R , Kollampallath Radhakrishnan S , Acharjee A 
Published: January 2025

Abstract

Background
The gut microbiome and its metabolites are key to understanding the pathogenesis of gastrointestinal diseases (GID) like gastric cancer (GC), inflammatory bowel disease (IBD), and colon cancer (CC), aiding in the identification of shared and disease-specific biomarkers for personalised interventions. This study used machine learning (ML) models, metabolic modelling and network analysis methods to assess the risk of developing one GID following another, especially as IBD patients are at higher risk of CC, and GC patients can develop CC.

Methods
Microbiome and metabolome datasets from Erawijantari et al. (GC), Franzosa et al. (IBD), and Yachida et al. (CC) were subjected to three ML models, eXtreme gradient boosting (XGBoost), Random forest (RF) and Least absolute shrinkage and selection operator (LASSO). The models were refined using Recursive Feature Elimination & Cross-Validation (RFECV) and LASSO. Trained models were applied for within and cross disease analyses using common microbes and metabolites. Microbial abundance analysis was conducted to identify compositional differences between the diseased and healthy patients. Microbial Community Modelling (MICOM) simulated microbial interactions to evaluate contributions to metabolite production. Using Weighted Gene Co-expression Network Analysis (WGCNA), A cluster dendrogram was generated to identify modules of highly correlated metabolic features based on co-expression patterns.

Results
ML models for the GC model had LASSO, achieving the highest AUC 0.96 [0.85-1.00]. For IBD, RF performed the best at AUC 0.93 [0.86-0.98]. CC model had XGBoost as the top performer AUC 0.85 [0.75-0.94]. Biomarkers from the GC model were used to predict CC and IBD outcomes, while biomarkers from IBD and CC models were similarly tested across diseases, having strong performance scores (Figure 2). Abundance analysis had lower levels of Bacteroidaceae in GC compared to healthy patients and higher Ruminococcaceae and Lachnospiraceae in IBD and CC. MICOM identified six metabolites in GC (adenosine, alanine, glycerophosphate, methionine, methionine sulfoxide, nicotinate), two in IBD (cholate, cytosine) and seven in CC (1-methyladenosine, alanine, glutamate, histidine, lactate, nicotinamide, tryptophan) all differentially produced by the selected microbes. WGCNA revealed four modules for GC (β=18,R²=0.91), eight modules for IBD (β=16,R²= 0.56), and two modules for CC (β=19,R²=0.27).

Conclusion
Despite study limitations, results suggest that the gut microbiome and its metabolites influence disease progression and aid in optimising therapeutic strategies, such as faecal microbiota transplantation (FMT), particularly in IBD and CC, potentially addressing both disease prevention and progression.
P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis
Authors: Eun C S , Jeong H W , Lee A R , Jung B W , Han D S 
Published: January 2025

Abstract

Background
Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model.

Methods
Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs.

Results
Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p.

Conclusion
In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.
P1319 Multi-omic modelling of antibiotic perturbed faecal microbial communities demonstrates reduced microbial resilience in IBD
Authors: Koentgen S , Zhang F , O’Brien C , Grimm M , Allen-Vercoe E , Hold G L 
Published: January 2025

Abstract

Background
Excessive antibiotic use is a risk factor in IBD, due to the impact on the gastrointestinal microbiota, but the extent of impact on microbial metabolite production is unknown. Here we investigate the impact of ciprofloxacin (CIP) and metronidazole (MTZ) on gut microbiota structure/function in a healthy donor and a new-onset therapeutic naïve IBD patient. We also investigate the use of autologous faecal microbiota transplant (aFMT) as a microbial therapeutic to assist recovery of the gut ecosystem.

Methods
Donor faecal specimens (IBD or healthy) were used to inoculate twin chemostat vessels. Following community stabilisation, vessels were dosed daily with CIP or MTZ for 7 days. In the healthy donor vessel, 4 doses of aFMT were administered over 7 days (post antibiotics) followed by a 7-day recovery. In the IBD vessels no FMT was administered. Vessels were sampled daily to monitor microbial profiles (16S rRNA sequencing) and short chain fatty acid (SCFA) profiles (GC-MS).

Results
CIP in the healthy vessel caused a significant depletion of acetate, butyrate and propionate, remaining significantly depleted during aFMT. CIP dosing also resulted in an enrichment of Escherichia-Shigella and Enterobacter and a loss of Akkermansia, Faecalibacterium and Bacteroides. During recovery acetate and propionate recovered whilst butyrate remained depleted (p=0.004). In the healthy MTZ vessel, acetate increased during antibiotic dosing and was restored following aFMT. Butyrate decreased during MTZ dosing and remained significantly decreased (p&lt;0.031). Propionate levels also reduced following MTZ but were found in highest abundance during aFMT and recovery phases (p&lt;0.038). Parabacteroides increased during MTZ dosing which subsequently decreased to stable abundance. Akkermansia was significantly increased in recovery phase compared to aFMT and stability phases.
In the IBD donor, CIP caused a significant reduction in 10 SCFAs and several taxa including Bacteroides and Dialister genera alongside an enrichment of Enterococcus, Lachnospiraceae, Anaerofilum and Eisenbergiella. MTZ treatment resulted in a less dramatic reduction in SCFAs. Microbial community changes included an enrichment of Escherichia-Shigella, Enterococcus and Parasutterella and a depletion of Alistipes and Dialister.

Conclusion
CIP and MTZ significantly depleted levels of beneficial genera and reduced the abundance of SCFAs. Neither donor community was able to fully restore composition or function. aFMT modulated the healthy donor microbial communities to a "new healthy". Further investigation into long-term antibiotic treatment and the use of microbial therapeutics is needed to fully understand this relationship in the context of IBD.
P1320 Oral highly-virulent pathogenic isolates aggravated colitis through gut microbiota-equol-ERβ axis
Authors: Chen J , Yang C , Xu Y , Zhao Y , Wu J , Liu Y , Chen N 
Published: January 2025

Abstract

Background
We isolated potential oral pathogens from IBD patients saliva and analyzed their virulence differences, hoping to elucidate the mechanism of different disease patterns in IBD patients.

Methods
A series of in vitro and in vivo experiments, whole-genome sequencing, 16S rRNA sequencing and non-targeted metabolomics sequencing were used to explore the pathogenicity of Streptococcus mutans (S.m) isolates.

Results
Our previous study indicated that the abundance of streptococcus in ulcerative colitis (UC) patients saliva was higher than healthy people. After over 1 year follow-up, we found that UC patients with poor disease state had higher proportion of S.m in saliva, and 31 S.m strains were further isolated from 25 UC saliva. Whole-genome sequencing showed that the virulence genes of S.m strains were related to immunity, metabolism and exotoxins. 9 strains with greater pro-inflammatory effects and barrier destroying ability were obtained based on microbe-cell co-culture. Subsequent animal experiments suggested that pro-inflammatory S.m strains significantly exacerbated intestinal inflammation of DSS mice, while non-pro-inflammatory S.m strains didn’t induce above effects.
The pro-inflammatory effects of pro-inflammatory S.m strains on DSS mice disappeared after the depletion of gut microbiota by antibiotics, and fecal bacteria transplantation (FMT) found that the intestinal inflammation of DSS mice transplanted with pro-inflammatory strains groups feces was more severe than that of non-proinflammatory mice, suggesting that intestinal microbiota is essential for the proinflammatory effects of S.m strains. 16S rRNA sequencing showed that α diversity of intestinal microbiota of pro-inflammatory strains groups mice was lower than that of non-proinflammatory mice. The level of equol was lower in pro-inflammatory groups compared to non-pro-inflammatory groups through non-targeted metabolomics sequencing. Subsequently, we further confirmed S-equol/R-equol both ameliorated DSS mice colitis, while estrogen receptor β (ERβ) antagonist inhibited the protective effect of equol partially. Molecular docking also confirmed the combination of equol and ERβ protein, of which the binding sites were GLU-305, Ph-356 and HIE-475.

Conclusion
This study found for the first time that the pro-inflammatory effects of S.m isolates are different, which may be related to gut microbiota-equol-ERβ axis.
P1325 Metabolic dynamics of the small intestinal microbiota upon nutritional interventions
Authors: Jordi S , Li J , Bärtschi I , Fasel N , Jacqueline W , Stecher B , Sauer U , Andrew M , Yilmaz B , Misselwitz B 
Published: January 2025

Abstract

Background
The human small intestinal microbiota, which plays a crucial role in intestinal function, remains poorly investigated due to limited accessibility.

Methods
We utilise the access via Ileostomies in a randomised cross-over trial with two nutritional interventions (high carb vs. high fat). Stoma effluent samples are collected from 70 stoma patients hourly (0-6h) after the intervention, along with blood and urine samples (0h, 3h, 6h). Stoma effluent samples from each study day are anaerobically cultured to generate a collection of small intestinal bacteria strains.

Results
We characterise the small intestinal microbiota through taxonomy (16S sequencing), biomass, and metabolome analysis. Shotgun metagenomic and mRNA sequencing are performed at selected timepoints. Our comprehensive “multi-omics" analysis involves identifying bacterial networks, interpreting their dynamics. In parallel, we have created a bacterial isolate catalogue (&gt;1000 isolates, ~200 species) form human samples to reproduce key interactions in vitro.

Conclusion
This study aims for a comprehensive analysis of small intestinal microbiota dynamics in the context of different nutritional interventions. The data and samples collected will enable hypothesis testing in vitro and lay the groundwork for future disease-specific investigations. Additionally, by establishing an extensive catalogue of well-characterised human-derived bacterial isolates, we created a resource for future experimental research projects.
P1329 Longitudinal study of the gut microbiome in patients with ulcerative colitis on biological treatment with vedolizumab
Authors: Robles Alonso V , Herrera-deGuise C , Mayorga L , Varela E , Martín Arranz M D , Margolles A , Sabater C , Casellas F , Guarner F , Borruel N 
Published: January 2025

Abstract

Background
In inflammatory bowel disease, altered microbial states of the gut microbial ecosystem could influence response to treatment. Our objective was to investigate the possibility of predicting response to vedolizumab using markers of the gut microbiome.

Methods
To this end, we analysed the characteristics of the gut microbiome using shotgun metagenomic sequencing in 21 patients with active ulcerative colitis, eligible for treatment with vedolizumab. The protocol included assessment of clinical activity and analysis of the microbiome in faecal samples prior to treatment and at weeks 12, 30, and 52 after initiation, and endoscopy at week 12. Remission was defined by SCAI &lt; 4, calprotectin &lt; 150 μg/g, C-reactive protein &lt; 0.5 mg/L, and Mayo index of 0 or 1. Sustain clinical remission was defined as previously at 52 weeks.
The study was funded by Takeda Farmacéutica España, S.A. EPIMUC study code: IISR-2015-101160 (FGA-VED-2016-01

Results
There were 9 responders and 12 non-responders. None of the patients with low microbial diversity (Chao1 &lt;75) achieved remission at week 14. The microbiomes of patients who did not achieve remission were more heterogeneous in taxonomy and metabolic pathways than the microbiomes of those who remitted (p&lt;0.05), which showed a stable microbiome composition profile during the remission induction phase. During treatment with vedolizumab, a progressive and significant increase (p&lt;0.05) in the relative abundance of some anti-inflammatory commensals (Bacteroides uniformis, Roseburia intestinalis, R. inulinivorans, R. faecis, Lachnospiraceae spp.) was only observed in patients who achieved sustained remission.

Conclusion
The stability and responsiveness of the gut microbial ecosystem could be a precondition, among others, for a satisfactory response to anti-integrin treatment
P1330 The gut microbiome at the onset of inflammatory bowel disease: A systematic review of the literature and unified bioinformatic synthesis of sequencing data from &gt;1000 treatment naïve patients
Authors: Rimmer P , Zhang F , Scott G , Hold G , Gordon M , Iqbal T , Hansen R 
Published: January 2025

Abstract

Background
There are few studies of the gut microbiome in new-onset IBD. We present a novel secondary bioinformatic re-analysis (BA) of sequence outputs mapped to latest microbial taxonomy derived from systematic review.

Methods
MEDLINE and Embase searches were performed for microbiome studies in pre-treatment IBD. Appraisal was completed with ROBINS-E. Available 16S rRNA sequence datasets were downloaded and missing datasets requested. Integrated datasets were run through a unified pipeline based in QIIME2 supplemented by phyloseq and DESeq2.

Results
From 12,264 studies, 10,804 abstracts and 217 full texts were screened. 31 studies were eligible; 18 met the requirements for BA. Most were low risk for bias, except uncontrolled confounding. Methodology varied extensively. Considering only amplicon data; samples originated from 1,743 unique individuals (including 678 Crohn’s disease (CD), 399 ulcerative colitis (UC), 123 ‘other’ IBD, 130 healthy, 405 symptomatic, and 8 familial controls) derived from 15 countries. DNA was extracted using 15 different kits, sequencing performed on 4 separate platforms targeting 10 different 16S rRNA hypervariable regions. There was a paucity of adult data, particularly mucosal biopsies.
Bacterial alpha diversity was reduced: in faeces in paediatric UC vs symptomatic controls (SC), in adult CD and UC vs HC and in paediatric SC vs HC (Figure 1).
In paediatric biopsies in CD vs SC, CD vs UC, SC vs UC (Figure 2).
Beta-diversity BA by Bray-Curtis demonstrated clear distinctions between faecal and mucosal biopsy communities, least evident in UC. Faecal communities separated by geography, though less evidently in biopsies.
Differential abundance analysis revealed enrichment of oral genera across sample types (Fusobacterium, Peptostreptococcus, Neisseria in CD; Haemophilus, Aggregatibacter, Peptostreptococcus, Porphyromonas, Neisseria, Gemella in UC). Short-chain fatty acid (SCFA) producers were diminished but less consistently across IBD phenotype and sample type.

Conclusion
This work demonstrates the utility of a combined systematic review/secondary data analysis approach to published microbiome datasets. Whilst synthesis remains challenging due to the methodological inconsistencies within these studies, this approach better accounts for these variations and presents a new way to consider this data. A reduction in bacterial diversity remains core to the IBD microbiome, though with more complexity than previously considered (SC&lt;UC in paediatric biopsies). Microbial community structure changes by sample type and geography. Enrichment of oral bacteria is consistent across IBD subtypes and sample types suggesting their importance in the disease. A deficit in SCFA producers may also be important.