bluuebunny/crossref_metadata_2025_split huggingface dataset:
A198 RELATIONSHIP BETWEEN HEPATIC GENE EXPRESSION AND MICROBIOME ACCORDING TO DISEASE SEVERITY IN OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: Ghorbani Y , Schwenger K , Teterina A , Liu Y , Lou W , Fischer S , Jackson T , Okrainec A , Allard J P 
Published: February 2024

Abstract

Background
Non-alcoholic fatty liver disease (NAFLD) ranges from steatosis to inflammation (steatohepatitis; NASH), fibrosis and cirrhosis. Development and progression of NAFLD/NASH is attributed to factors such as obesity and metabolic syndrome as well as intestinal microbiome (IM) but research is limited on the relationship between IM and hepatic gene expression.

Aims
Our objective was to assess in obese patients;1) the transcriptome signature of NAFLD and fibrosis and; 2) determine the relationship between the identified genes and IM.

Methods
Biochemical and anthropometric measurements as well fecal samples for IM shotgun metagenomic sequencing were collected in those with obesity undergoing bariatric surgery. Liver histology was assessed using Brunt scoring system and hepatic transcriptome was assessed using RNA-Seq. Differences in biochemical data and IM were determined using Kruskal-Wallis test followed by Wilcoxon ranked sum test. Differentially expressed genes (DEGs) in the liver were determined using DESeq2 package in R and had |log2 foldchange| ≥1 with adjusted p-value ampersand:003C0.05. Spearman correlation coefficients was used to evaluate the association between significant DEGs and significant bacteria and adjusted using Benjamini-Hochberg.

Results
93 patients had both transcriptome and IM data. Of those, 27 had normal liver obese (NLO) and 66 had NAFLD (including 31 NASH). In those with NAFLD, 19 had no fibrosis (F0) and 47 had presence of fibrosis (F1-F4). We found 71 significantly different DEGs (e.g. PPP1R3G ) in NASH vs NLO and 12 (e.g. THBS2 and GLI2) in NAFLD with presence of fibrosis vs no fibrosis. Those with NASH generally had higher Escherichia coli, Blautia hansenii and lower Alistipees putredinis. Those with NAFLD and fibrosis had increased E. coli and reduced Eubacterium ventriosum and A. putredinis. In the preliminary analysis of NASH vs NLO, B. hansenii negatively correlated with glucose homeostasis-related PPP1R3G. In those with NAFLD, A. putredinis correlated negatively with THBS2 (i.e. Thrombospondin-2) and, in patients with NAFLD and fibrosis, E. coli correlated positively with GLI2 (related to activation of hepatic stellate cells).

Conclusions
DEGs were associated with specific bacteria in NASH or fibrosis. Next steps include analyzing the microbial metagenomic pathways as well as metabolites and determine the relationship between the IM, hepatic transcriptome and metabolites according to disease severity.

Funding Agencies
CIHRAmerican College of Gastroenterology Bridge Award, BBDC Tamarack Graduate Award in Diabetes Research
A208 ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR BARRETT’S NEOPLASIA: CLINICAL OUTCOMES AND MID-TERM FOLLOW-UP AT A CANADIAN TERTIARY REFERRAL CENTER
Authors: Fujiyoshi Y , Khalaf K , Natalia C , Mosko J , May G , Teshima C 
Published: February 2024

Abstract

Background
Endoscopic submucosal dissection (ESD) is an established technique for resecting early gastrointestinal neoplastic lesions. However, for Barrett’s neoplasia treatment, piecemeal EMR has been the standard approach, leaving the efficacy of ESD for Barrett’s neoplasia unclear.

Aims
To assess the outcomes of Barrett’s neoplasia treated with ESD at a tertiary center in Canada.

Methods
This is a single center, retrospective study. All patients aged over 18 who underwent ESD for Barrett’s neoplasia at St. Michael’s Hospital between December 2017 and August 2023 were included. Primary outcomes were En-bloc, R0, curative resection, and recurrence rates, while secondary outcomes focused on the adverse event rate.

Results
Of the 72 patients studied (mean age 67.7 years; 90% male), 31.9% (23/72) were SSBE and 68.1% (49/72) were LSBE. The mean±SD lesion size was 4.5±3.4 cm, with circumferential occupancy at 53.4±23.9 %. Paris classifications were as follows: 0-Is: 8 (11.1%), 0-IIa: 26 (36.1%), 0-IIb: 9 (12.5%), 0-IIc: 6 (8.3%), 0-IIa+IIc: 13 (18.6%), 0-IIa+Is: 10 (13.9%). The mean operation time stood at 144.4 (75.3) minutes. Adverse events comprised deep mural injury (4.1%) and delayed bleeding (2.8%). Pathology findings showed high-grade dysplasia in 6.9% and adenocarcinoma in 93.1%, further differentiated as: well-differentiated (55%), moderately differentiated (33%), and poorly differentiated (12%). The invasion depth was intramucosal in 76%, SM1 in 6%, and SM2-SM3 in 18%. Lympho-vascular invasion was present in 22%. En-bloc, R0, and curative resection rates were 96% (69/72), 82% (59/72), and 64% (46/72), respectively. Of the curative resection patients, 42 have completed follow-up EGD, with 11.9% (5/42) showing persistent dysplasia at first follow-up. These were treated by either EMR (4 cases) or ESD (1 case), leading to a 100% (42/42) complete remission of dysplasia (CRD) rate with median follow-up time of 127 (68-190) days. After achieving CRD, local recurrence was found in 2.4% (1/42) with a median follow-up time of 289 (136-524) days. This recurrence post-CRD was successfully treated with EMR, regaining CRD.

Conclusions
Our study showcases the Canadian experience of using ESD for Barrett’s neoplasia at a large single tertiary referral center. Given the challenging demarcation lines in Barrett’s neoplasia and the frequent presence of metachronous lesions, even with curative resection, 11.9% showed persistent lesions during the first follow-up. However, these lesions were treatable endoscopically, with 100% eventually achieving CRD. Although there was a 2.4% recurrence rate post-CRD, this too could be managed endoscopically. Overall, the mid-term outcomes of treating Barrett’s neoplasia with ESD are promising.

Funding Agencies
None
A209 ESOPHAGEAL EPIDERMOID METAPLASIA: ADVOCATING FOR A PRIMARY ENDOSCOPIC SUBMUCOSAL DISSECTION APPROACH
Authors: Gilhotra R , Zarrin A , Jiang S X , Xiong W , Shahidi N 
Published: February 2024

Abstract

Background
Esophageal epidermoid metaplasia (EM), or leukoplakia, is a rare finding on endoscopy; typically seen incidentally as a white plaque and histologically characterized by orthokeratosis. The link between EM and squamous neoplasia has been identified. There is no consensus on the management of EM.

Aims
To present a case of circumferential esophageal EM managed with endoscopic submucosal dissection (ESD).

Methods
Case report and review of the literature

Results
A 56-year-old female with a known history of EM was referred for consideration of ESD due to dysplastic progression confirmed on histopathology. Previous attempts at eradication included argon plasma coagulation and staged band mucosectomy. Fully circumferential ESD was performed over a 100mm segment in the mid esophagus using the double tunnel technique. Histopathology revealed multifocal low-grade squamous intraepithelial neoplasia within epidermoid metaplasia with negative margins.

Conclusions
Esophageal epidermoid metaplasia may increase the risk of squamous cell carcinoma. There are no consensus recommendations regarding its management with previous described strategies including surveillance and eradication with radiofrequency ablation and band mucosectomy. ESD for epidermoid metaplasia has not been described; however, given the overall efficacy, efficiency, safety and now widespread availability of this technique a primary ESD approach should be considered.

Funding Agencies
None
A227 EXPLORING THE ROLE OF MICROBIAL AND GENETIC FACTORS IN DEFINING THE INTESTINAL IMMUNE SYSTEM USING A HUMANIZED GNOTOBIOTIC MOUSE MODEL
Authors: Bayer G , Tsankov B K , Samman B , Foerster E , Winsor N , Visser G V , Hakim S , Allen-Vercoe E , Philpott D 
Published: February 2024

Abstract

Background
Studies of the gut microbial ecosystem and its role in disease are often complicated by the intricate network of interactions between its microbial members and the host. Therefore, mouse models in which the microbiota diversity can be strictly controlled, and the functional potential be easily assessed, are needed.

Aims
Establishing a taxonomically and functionally diverse human gnotobiotic microbiota that recapitulates many microbe-host interactions of the complex human microbiome. To validate the effects of the defined bacterial gut community on the host, we will assess host physiology, intestinal immunity and the response to inflammatory stimuli.

Methods
Germ-free (GF) mice were inoculated with a defined bacterial community isolated from the stool of a healthy human donor. Stability of colonization across multiple generations and spatial organization of the bacterial community in the intestine were assessed using 16S rRNA gene sequencing and species-specific quantitative PCR. Immune cells were isolated from the colonic lamina propria and characterized by flow cytometry.

Results
Inoculated GF mice were reproducibly colonized with 8 bacterial species, collectively termed Human Defined Community 1 (HDC1). The HDC1 is vertically transmitted from mothers to offspring and the relative abundances remain stable in the colony over an extended period in a gnotobiotic isolator. We observed spatial stratification of the HDC1 microbiota between the small intestine and colon or cecum. HDC1 mice form a colonic inner mucus layer comparable in thickness to SPF mice suggesting physiological spatial organization of the bacterial community over the cross-sectional axis of the colon. Characterization of colonic lamina propria immune cells in HDC1 mice revealed myeloid and lymphoid cell abundances closely resembling those of mice harboring a complex microbiota (specific pathogen-free [SPF] mice), including normal macrophage and dendritic cell counts and normal proportions of CD4+ cells (regulatory T, Th1 and Th17 cells). Finally, we showed that HDC1 mice can be transplanted with human gut commensals and Crohn's disease (CD)-associated bacteria, demonstrating the tractability of this human defined microbiota.

Conclusions
In summary, HDC1 gnotobiotic mice are stably colonized with a human defined bacterial community and harbor an intestinal innate and adaptive immune system similar to SPF mice. Therefore, HDC1 mice represent a reliable and tractable tool for host-microbe interaction studies. Ultimately, we will employ the HDC1 model to decipher the role of Nod2 – the strongest genetic risk factor for CD development – in shaping both the microbiota and host immunity.

Funding Agencies
CIHROGS
A229 DRUG PERSISTENCE WITH THERAPY OF ADALIMUMAB BIOSIMILAR, IDACIO, IN INFLAMMATORY BOWEL DISEASES
Authors: Cheung S , Kudaeva F , Heidari P , Truong D 
Published: February 2024

Abstract

Background
For post marketed medicine, drug persistence could be used as an indication for effectiveness and safety in routine clinical care over time. Non-adherence and non-persistence to treatment are associated with disease flares and may lead to disease progression among patients with inflammatory bowel diseases (IBD) in real-life.

Aims
The aim of this analysis was to explore drug persistence with an adalimumab biosimilar, Idacio, in IBD patients using the data collected by Fresenius Kabi patient support program (KabiCare) in Canada.

Methods
Patients with IBD enrolled in KabiCare and received at least one dose of adalimumab biosimilar, Idacio, were followed up from February 2021 to September 2023 in Canada. Medication initiation date and stop date, disease types (Crohn’s disease [CD], and ulcerative colitis [UC]) and patient treatment (categorized by naïve to biologic,or switched from other biologics) were recorded in the database. The stop date was the date when KabiCare was informed that medication was discontinued. The patients continuing medication were censored at the maximal follow-up date of analysis, September 12, 2022. Log-rank tests were used for KM (Kaplan-Meier) plot comparison to examine if there were differences in medication adherence between CD and UC, and between naïve group vs. switch group by disease.

Results
The study sample consisted of 1049 patients: 830 (79.1%) had CD, and 338 (32.2%) were in naïve group. KabiCare followed patients with CD for a median time of 512 days (interquartile range: 285-673 days; maximum: 895 days), and followed patients with UC for a median time of 492 days (interquartile range: 183-672 days; maximum: 925 days). At 800 days after starting the medicine, the drug persistence probability was similar for patients with CD and UC (At day-800: 76.6% vs. 67.6%, p=0.07). Among patients with CD, the drug persistence probability was higher in the switch group compared to naïve group (At day-800: 78.9% vs. 71.7%, p=0.0028). Among patients with UC, the drug persistence probably was similar in the switch group compared to naïve group (At day-800: 78.4% vs. 62.3%, p=0.34).

Conclusions
The drug persistence of adalimumab biosimilar, Idacio, was over 76% in patients with CD and over 67% in patients with UC 800 day after therapy initiation. Compared to patients in the naïve group, patients in the switch group were more likely to stay on adalimumab therapy.

Funding Agencies
None
A241 CORRELATION BETWEEN PLASMA IGA LEVEL AND BIOLOGICAL THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Lee B , Hsu J , Tsai T 
Published: February 2024

Abstract

Background
IgA is the predominant antibody class secreted by intestinal immune cells. However, the level of plasma IgA in Inflammatory Bowel Disease (IBD) patients under medical treatment remains unknown. Therefore, our study aimed to investigate the relationship between plasma IgA concentration in IBD patients under biological therapy.

Aims
To assess the correlation between plasma IgA level in IBD patients under biological therapy.

Methods
We collected data from outpatient clinics at our hospital, including 12 IBD patients, comprising 4 patients with Crohn's disease (CD) and 8 patients with Ulcerative Colitis (UC). Data was collected between 2020 and 2023. We measured plasma IgA concentrations both before initiating biologic therapy and at the 14th week of biological treatment (4 under Adalimumab and 8 under Vedolizumab). Additionally, we compared baseline plasma IgA levels between 24 IBD patients (7 CD and 17 UC) and 24 healthy individuals. Student T test was used for statistical analyze.

Results
The average baseline plasma IgA level was significantly higher in IBD patients (2134±187.2 ug/ml, mean ± standard error) when compared to healthy individuals (1346± 114.8 ug/ml, p=0.0008). In the view of CD and UC, the baseline plasma IgA level was 2179±439.4 ug/ml and 2116±203.1 ug/ml, respectively. Baseline plasma IgA level also showed statistical significantly higher in CD and UC compared to healthy individuals (p=0.0063, p=0.0005, respectively), and without difference between UC and CD patients (p=0.8824) (Figure 1A).
Furthermore, we investigated the impact of biological therapy on plasma IgA levels in IBD patients, finding a significant decrease in plasma IgA levels after biological therapy (2182±254.7 ug/ml to 1824±135.5 ug/ml, p=0.0181). Similar trend was noted in UC patients under biological therapy with borderline statistical significant (2141± 307.7ug/ml to1809±173.3ug/ml, p=0.0561), but not found in CD patients (2265±518.3 ug/ml to 1855±247.5 ug/ml, p= 0.1333)(Figure 1B).

Conclusions
We found that baseline plasma IgA level was higher in IBD patients compared to healthy individuals. Besides, plasma IgA level decreased after biological therapy in IBD patients, especially in UC patients. These findings suggest that plasma IgA level may be a potential biomarker for IBD patients.

Funding Agencies
None
A251 GUT-SPECIFIC DOWNREGULATION OF INTERFERON-LAMBDA RESPONSES OCCURS IN INFLAMMATORY BOWEL DISEASES
Authors: Ogungbola O , Mahmood R , Ouyang J , Vu V , Nguyen N , Liu X , Bittorf K , Lamb S , El-Matary W , Bernstein C , Wine E , Tyrrell L D , Armstrong H K , Santer D 
Published: February 2024

Abstract

Background
Inflammatory bowel diseases (IBD) affect 1:140 Canadians, resulting in significant inflammation and gut damage. Unlike type I and II interferons (IFNs), the most recently discovered IFNs, interferon-lambdas (IFN-λs), uniquely downregulate gut inflammation and promote gut healing in mouse models. However, it remains unknown if the important anti-inflammatory IFN-λ signaling pathways induced downstream of the IFN-λR1/IL-10RB heterodimeric receptor are altered in IBD.

Aims
To compare intestinal and peripheral IFN-λR levels and responses in people with active or remission IBD and those without IBD. We hypothesized that intestinal IFN-λR1 levels and downstream activities are decreased in people living with IBD, which could contribute to IBD pathology (gut inflammation and mucosal damage).

Methods
During routine colonoscopy, uninflamed biopsy samples were obtained from the terminal ileum and sigmoid colon. IFN-λR1 levels were quantified in intestinal biopsy and blood samples from persons with or without IBD (n=12 adults and n=12 pediatric) by immunohistochemistry and flow cytometry. Fresh intestinal biopsies were also cultured ex vivo for 24 hr in media +/- IFN-λ3 and gene expression was quantified by RT-qPCR.

Results
In IBD gut tissues, a significant decrease in IFN-λR1+ cells was more prominent in IBD patients with active disease (pampersand:003C0.01, 30-50% reduction). The decrease was more prominent in IBD patients with active disease. Consequently, there was a significantly lower IFN-λ-driven upregulation of genes such as IFIT1 and MX1 in IBD as compared to non-IBD tissues (pampersand:003C0.05, 4-7-fold reduction). Interestingly, IFN-λR1 levels were not decreased in peripheral blood immune cells, indicating the dysregulation of IFN-λR responses is likely gut-specific.

Conclusions
Our findings demonstrate that people living with IBD have dysregulated IFN-λ responses in the gut which could lead to the lower induction of key anti-inflammatory pathways. This work supports the further study of mechanisms regulating the IFN-λ system to develop strategies to restore and promote IFN-λ responses as a novel potential future IBD therapy.

Funding Agencies
University of Manitoba, Weston Family Foundation, The Children's Hospital Research Institute of Manitoba.
A253 BEHAVIOUR CHANGE CONSIDERATIONS TO IMPROVE PHYSICAL ACTIVITY PARTICIPATION AMONG INDIVIDUALS WITH QUIESCENT AND MILDLY ACTIVE IBD – A QUALITATIVE STUDY
Authors: Oketola B , Webber S , Singh H , Kredentser M , Reynolds K , Restall G 
Published: February 2024

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Please acknowledge all funding agencies listed below
Funding Agencies
CAGPfizer
A254 CANAGLIFLOZIN EXACERBATES CHEMICALLY INDUCED COLITIS WHEN COMBINED WITH A HIGH SUGAR DIET
Authors: Madsen K , Omeltchenko T , Hotte N , Thiesen A , Villaflor B , Cheng C 
Published: February 2024

Abstract

Background
Consumption of high-sugar diets exacerbates inflammation and hinders the healing process in animal models of acute colitis. Canagliflozin (CANA) is a sodium glucose cotransporter-2 (SGLT2) inhibitor primarily used for the management of type 2 diabetes and cardiovascular disease. CANA has demonstrated the ability to suppress human T cell and macrophage effector function and to improve inflammation in rat colitis models. Based on these findings, we hypothesized that CANA would mitigate the deleterious effects of a high sugar diet in a DSS colitis model through its effects on immune effector cells.

Aims
The aim of this study was to examine the effects of a high sugar diet and CANA administration on colonic inflammation in an animal model of acute colitis.

Methods
Adult wild-type male and female 129/SvEv mice were placed on standard chow or a high-sugar diet (HSD) containing 50% sucrose (AIN76A) ± CANA (10mg/kg) gavaged daily (n=4-6 for each group). Following three days on the respective diet, mice received 1.8-2% dextran sodium sulfate (DSS) in their drinking water for 5 days, followed by water alone for 4 days. Disease Activity Index (DAI) was computed daily based on changes in animal weight, stool consistency, and blood in stool. Colonic tissues were evaluated for histological changes, weight-to-length ratio, and cytokine levels using the MesoScale discovery platform.

Results
Mice on the HSD had increased severity of colitis compared with chow fed mice as evidenced by enhanced DAI, increased weight loss, and increased levels of colonic TNFα (pampersand:003C0.02). Response to CANA treatment was both sex and diet dependent. Contrary to our hypothesis, CANA treatment increased severity of colitis in male mice on the HSD as evidenced by increased DAI and delayed healing with increased enterocyte injury and increased levels of lamina propria neutrophils and lymphocytes. CANA treatment did not exacerbate disease severity in females on the HSD but did delay healing as evidenced by increased lamina propria neutrophils and lymphocytes and worse enterocyte injury. These effects were not observed in mice that were fed standard chow diets with CANA.

Conclusions
A high-sugar diet significantly exacerbates chemically induced colitis and delays healing. This effect is intensified when combined with CANA, especially in male mice. These findings indicate that effects of SGLT2 inhibitors on colonic inflammation can be modulated by both dietary intake and sex.

Funding Agencies
CCC