bluuebunny/crossref_metadata_2025_split huggingface dataset:
A8 DIETARY TRYPTOPHAN MODULATES KYNURENINE AND INDOLE PRODUCTION IN HEALTHY INDIVIDUALS
Authors: Rueda G H , Causada-Calo N , Borojevic R , Nardelli A , Constante M , Loonen L , Wells J , Sokol H , Verdu E , Bercik P 
Published: March 2021

Abstract

Background
Tryptophan is an essential amino acid that is transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity, mood and circadian rhythms. In particular, indoles, produced by gut bacterial metabolism of tryptophan, have recently gained central attention. Indoles are activators of the aryl hydrocarbon receptor (AhR), which is crucial for the maintenance of intestinal homeostasis and immunity. Tryptophan supplementation in fortified foods have been advocated to prevent chronic inflammatory conditions, from autism to chronic inflammation. However, whether dietary tryptophan supplementation affects immune function, tryptophan metabolic pathways and gastrointestinal symptoms in healthy subjects, is unknown.

Aims
To assess whether tryptophan supplementation, in healthy subjects on a low tryptophan diet, induces changes in microbiota-derived metabolites (indoles), host cytokine production or gut symptoms.

Methods
We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy individuals, between 18 and 75 years old, following a regular diet. Subjects were instructed to start a standardized low tryptophan diet and were randomly assigned to a 3-week tryptophan supplement (3gr/day) or placebo. After a 2-week washout period, subjects were crossed over to the opposite 3-week intervention arm. Self-administered questionnaires (GSRS, DASS21 and HADS) were used to assess gastrointestinal symptoms and mood/anxiety/stress. Stool, urine and blood samples were collected to measure tryptophan metabolites (kynurenine pathway and indoles) and cytokines.

Results
Supplementation of tryptophan was well tolerated and no changes in gastrointestinal symptoms or mood/anxiety were found. Compared with placebo, tryptophan supplementation increased urinary and plasma levels of indoleamine 2,3-dioxygenase (p= 0.002 and p= 0.02, respectively), a key enzyme in the kynurenine pathway, and of several indoles (p= 0.0008 and p= 0.01, respectively), suggestive of activation of microbial and host metabolic pathways. However, there were no measurable changes in the host cytokine production. There was a positive correlation between fecal kynurenine levels and anxiety and depression scores, suggesting that microbial metabolites may impact host behavior in humans.

Conclusions
Dietary tryptophan supplementation in healthy individuals was safe and had a measurable effect on microbial and host metabolism, mainly kynurenine and indole pathways, with known immunomodulatory properties. Although no effects on cytokine production were found, further studies are warranted to investigate tryptophan supplementation in disorders with altered AhR pathway, such as inflammatory bowel disease, metabolic syndrome and celiac disease.

Funding Agencies
None
A32 EMPAGLIFOZIN IMPROVES GASTROINTESTINAL INFLAMMATION IN A MOUSE MODEL OF COLITIS
Authors: Madsen K , Dang H , Hotte N , Mocanu V , Ferdaoussi M , Thiesen A , Dyck J 
Published: March 2021

Abstract

Background
Empagliflozin (EMPA) is a highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor and is increasingly being utilized as an antihyperglycemic agent in the management of type 2 diabetes. Interestingly, it has been demonstrated in human trials that EMPA treatment exerts potent cardioprotective effects by reducing cardiac inflammation independently of glycemic control. Further, EMPA has also been shown to suppress LPS-induced renal and systemic inflammation in an animal model. Based on these findings, we hypothesized that EMPA treatment may also be effective in reducing gut inflammation.

Aims
The aim of this study was to examine the effects of treatment with EMPA on gastrointestinal inflammation in an animal model of inflammatory bowel disease and to determine mechanistic insights regarding its direct effects on gut cytokine secretion.

Methods
Adult male and female IL-10-/- mice with established colitis were treated with a daily gavage of EMPA (10mg/kg; n=10) or vehicle (n=10) for 14 days. Disease activity was assessed by measurement of mouse weight, colonic weight and length, histological score, cytokine levels in colonic homogenate and lipocalin-2 levels in stool. To examine for possible direct effects of EMPA, colonic explants from wild-type (n=8) and IL-10-/- (n=8) mice were incubated with increasing doses of EMPA (0.1–5 µM) ± LPS (10µg/ml) for 2 hours and tissue levels of IL-1β and TNFα protein measured by ELISA.

Results
After 14 days EMPA treated IL-10-/- mice had a significant improvement in colonic inflammation as evidenced by decreased colonic weight to length ratio (p=0.019), decreased fecal lipocalin-2 (p=0.03), as well as decreased enterocyte injury (p=0.01), decreased lamina propria neutrophils (p=0.01) and decreased total histological score (p=0.006). EMPA treated mice also maintained their weight over the 14 days while untreated mice continued to lose weight (p=0.04). There were no significant differences in colonic homogenate levels of TNFα, IL-1β, or IL-6 or in blood glucose levels between EMPA-treated mice and controls. In addition, EMPA did not suppress levels of basal or LPS-induced TNFα and IL-1β in colonic explants from either wild-type or IL-10-/- mice suggesting that the beneficial effects in IL-10-/- mice were not due to direct effects of EMPA on colonic TNFα or IL-1β cytokine levels.

Conclusions
EMPA treatment dramatically improved histologic and fecal inflammatory markers and maintained body weight in adult IL-10-/- mice with established colitis. These findings suggest further investigations into the effects of EMPA in treating gut inflammation are warranted.

Funding Agencies
CAG, CIHR
A34 ANTIBIOTIC TREATMENT AND ORAL IRON SUPPLEMENTATION SHAPE THE COMPOSITION, RECOVERY AND FUNCTION OF THE GUT MICROBIOTA
Authors: Cuisiniere T , Oliero M , Hajjar R , Calve A , Fragoso G , Santos M M 
Published: March 2021

Abstract

Background
Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. However, the combined effect of antibiotics and luminal iron in the gut on the microbiota and intestinal homeostasis remains unknown.

Aims
We aim to characterize the dynamics of gut microbiota composition and recovery from antibiotic exposure under iron-sufficient and iron-supplemented diets in mice. We will investigate how microbial shifts induced by antibiotics and iron influence the function of the gut microbiota and metabolites in the gut.

Methods
Mice were subjected to antibiotic treatment with different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA sequencing before and after antibiotic exposure and during the recovery period. Gut microbiota functions were inferred by using the PICRUSt2 prediction tool, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry.

Results
Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Four bacterial species characterized as CRC markers and/or CRC initiators were significantly more abundant, and nitrogen and pentose phosphate metabolism were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate, and was independent of luminal iron concentration. For mice recovering from antibiotics under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut.

Conclusions
Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota and may lead to modifications in the management of anemia in patients with CRC.

Funding Agencies
CIHR Bourse de Mérite Rougier-Armandie en recherche médicale de la Faculté de médecine
A42 INULIN PROMOTES POLYPS DEVELOPMENT IN APC
MIN/+ MOUSE COLONIZED BY ESCHERICHIA COLI NC101
Authors: Oliero M , Cuisiniere T , Hajjar R , Fragoso G , Calve A , Santos M M 
Published: March 2021

Abstract

Background
Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and facilitate the progression of colorectal cancer through cellular senescence and chromosomal abnormalities.

Aims
In this study, we investigated the impact of inulin, a prebiotic able to modulate bacterial metabolism, in a colorectal cancer model, ApcMin/+mice, colonized by colibactin-producing E. coli strain NC101.

Material & methods
Apc Min/+ mice were subjected to oral gavage with PBS (control) or 108 cfu of E. coli NC101 after a week of receiving a 2% dextran sulfate sodium solution in drinking water. Mice were fed a diet supplemented with 10% cellulose (control) or 10% inulin for 4 weeks. During necropsy, the number of polyps in the duodenum, jejunum, ileum, and colon was counted. Tumors in the colon were graded and the erythroid parameters were measured.

Results
We showed that the inulin diet increased the number of polyps in the ileum compared to cellulose. Moreover, mice colonized with E. coli NC101 and on the inulin diet presented severe anemia associated with an increasing number of polyps in the duodenum, jejunum, and ileum compared to mice supplemented with cellulose.

Conclusions
Our results suggest that, in vivo, inulin promotes polyp development in the small intestine of ApcMin/+ mice colonized by pks+ E. coli strain NC101.

Funding Agencies
CIHRNSERC
A65 ENDOSCOPIST-TARGETED INTERVENTIONS TO OPTIMIZE ADENOMA DETECTION RATE - A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Arora A , McDonald C , Iansavitchene A , Brahmania M , Sey M 
Published: March 2021

Abstract

Background
Adenoma detection rate (ADR) has emerged as the strongest quality assurance metric that has consistently been shown to be inversely associated with the development of colorectal cancer after colonoscopy. Unfortunately, marked variability in ADR exists among endoscopists. A multitude of interventions targeted at endoscopists to optimize their ADR have been reported, including but not limited to withdrawal time, in room observers, physician report cards, and quality improvement and training programs. However, it is unclear which of them are truly effective.

Aims
We performed a systematic review and meta-analysis of the literature to evaluate the effectiveness of endoscopist-targeted interventions to improve adenoma detection rate (ADR) or polyp detection rate (PDR).

Methods
Systematic searches of major databases were conducted through to March 2018 to identify potentially relevant studies. Both randomized controlled trials and observational studies were included. Data for ADR and PDR were analyzed on the log-odds scale using a random-effects meta-analysis model using restricted maximum likelihood (with Mantel-Haenszel fixed-effect meta-analysis used for fewer than 4 studies). Statistical effect-size heterogeneity was assessed using a Chi2 test and quantifying the relative proportion of variation using the I2 statistic. Publication bias was assessed by the Harbord regression test.

Results
From 4299 initial studies, 24 were included in the systematic review and 13 were included in the meta-analysis representing a total of 55,090 colonoscopies. Physician report card interventions (7 studies) and withdrawal time focused interventions (6 studies) were meta-analyzed. The pooled odds ratio for ADR for report card interventions was 1.31 (95% CI: 1.15, 1.50; p&lt;0.0001), favoring report cards to detect more adenomas. Statistical heterogeneity was detected with substantial relative effect-size variability (Chi2, p&lt;0.0001; I2=80.1%). No statistical evidence of publication bias was found. 6 studies reported data for PDR using withdrawal time focused interventions, with 3 of these reporting data on ADR. The pooled odds ratio for ADR was 1.02 (95% CI: 0.86, 1.22; p=0.81) and for PDR was 1.07 (95% CI: 0.88, 1.31; p=0.51) which were not statistically significant. Statistical heterogeneity was detected in both groups (Chi2, p&lt;0.001; I2=82.2% for ADR and I2=89.4% for PDR) and there was statistical evidence of publication bias. Figures 1 and 2 represent Forest plots for the effect of pre-and post-report card and withdrawal time focused interventions on ADR.

Conclusions
Our study provides evidence that the distribution of colonoscopy quality report cards to physicians significantly improves overall ADR and should strongly be considered as part of quality improvement programs aimed at optimizing colonoscopy performance.

Funding Agencies
None
A69 THE EFFECT OF COVID-19 PANDEMIC ON CURRENT AND FUTURE ENDOSCOPIC PERSONAL PROTECTIVE EQUIPMENT PRACTICES: A NATIONAL SURVEY OF 77 ENDOSCOPISTS
Authors: Sun W , El Hafid M , Dang J , Mocanu V , Lutzak G , Sultanian R , Wong C , Karmali S 
Published: March 2021

Abstract

Background
Personal protective equipment (PPE) guidelines serve to protect healthcare providers and patients from harmful biohazards. With the rise of the 2019 SARS-CoV-2 disease (COVID-19), many institutions have mandated strictly enforced endoscopic PPE guidelines. We currently do not know how current practitioners perceive these mandates or how they will influence their practice long-term.

Aims
We aimed to survey the PPE practices among endoscopists across Canada and compare their perceived differences in practice between the pre- and post-COVID-19 pandemic eras. We hypothesize that the PPE guidelines during the pandemic will influence changes in PPE practices in endoscopy.

Methods
A 74-item questionnaire was emailed from June 2020 to September 2020 to all members of the Canadian Association of Gastroenterologists and the Canadian Association of General Surgeons through newsletters. The survey was created by expert consensus and distributed using the REDCap software. Survey questions collected basic demographics and differences between PPE practices pre- and post-COVID-19 pandemic eras. PPE practices were categorized into four endoscopic procedure types: diagnostic or therapeutic, and upper or lower gastrointestinal endoscopy. Individual outcomes were reported as rates, or ranges when evaluating for all procedure types.

Results
A total of 77 respondents completed the survey with the majority of respondents aged 40–49 (34 [44.2%]) and identifying as Gastroenterologists (54 [70.1%]). Gender was evenly split (38 females [49.4%] versus 39 males [50.6%]). In the pre-pandemic era, the majority of endoscopists wore gowns (91.0–93.9%) and all endoscopists wore gloves (100%). However, the majority of endoscopists did not wear surgical masks (20.9%-31.3%), N95 respirators (1.5%-3.2%), face shields (13.4%-33.9%), eye protection (13.4%-21.3%), or hair protection (11.1%-12.5%).
In the post-pandemic era, endoscopists reported a plan to dramatically change their pre-pandemic practices and adopt current PPE mandates. All endoscopists reported a plan to fully gown and glove (100%) with the majority reporting they will continue wearing surgical masks (87.7%-90.5%), face shields (57.8%-75.0%), and hair protection (50.8%-53.8%). However, the majority reported a plan to decrease universal use of N95 respirators (6.5%-23.7%) or eye protection (36.5%-40.0%). Over half of the respondents reported changing their practice from no masking pre-pandemic to implementing routine masking.

Conclusions
The COVID-19 pandemic has changed the attitudes of many endoscopists regarding future PPE use in routine endoscopy. Ongoing studies comparing the rates of transmission of hospital-acquired infections in the setting of endoscopy are needed to develop a new post-pandemic PPE consensus.

Funding Agencies
None
A93 VOLUME OF EMR EXPOSURE IN TRAINING IS CORRELATED WITH POLYPECTOMY COGNITIVE COMPETENCE AMONGST RECENT GASTROENTEROLOGY GRADUATES
Authors: Jeyalingam T , Walsh C M , Grover S C , Heitman S , Mosko J 
Published: March 2021

Abstract

Background
Competence in performing polypectomy is increasingly appreciated as a colonoscopy quality metric, as incomplete resection can lead to post-colonoscopy colorectal cancer, particularly for polyps removed using piecemeal endoscopic mucosal resection (EMR). The relationship between training experiences and cognitive competence in polypectomy has not been previously described.

Aims
We aimed to examine associations between training and assessment experiences, self-reported comfort, and cognitive competence in polypectomy amongst recent graduates of Canadian gastroenterology training programs.

Methods
An online survey was distributed to recent GI graduates (≤5 years in independent practice). The survey comprised 4 sections: (1) demographics; (2) training and assessment experiences in colonoscopy, polypectomy, and EMR; (3) self-reported comfort in performing aspects of polypectomy outlined in the Direct Observation of Polypectomy Skills Assessment Tool; and (4) performance on a 22-item multiple choice quiz intended to assess cognitive competence in polypectomy (items and correct responses to which were determined a priori based on agreement of two experts). Data was analyzed using descriptive statistics and associations between predictors (demographics, training/assessment experiences, self-reported comfort) and outcomes (quiz score) were assessed using multiple linear regression.

Results
There were 28 survey respondents, comprising 13 (46%) who trained in advanced endoscopy, 5 (18%) in hepatology, 2 (7%) in motility, 1 (4%) in IBD, 1 (4%) in nutrition, and 6 (21%) with no advanced training. This cohort had a mean (SD) duration in independent practice of 29.0 (18.4) months. Their mean (SD) annual volume of colonoscopy, polypectomy, and EMR in independent practice was 530 (221), 182 (76), 28 (16), respectively and they had completed 525 (203) colonoscopies, 146 (92) polypectomies, and 23 (20) EMRs in their prior training. Their mean (SD) quiz score was 71.9% (13.2%). ANOVA revealed significant score differences based on fellowship history, with those trained in advanced endoscopy achieving the highest scores (81.1%, P=0.01). Multiple linear regression revealed that the number of EMRs completed during training was significantly correlated with quiz performance (B=0.60, P=0.03).

Conclusions
EMR experience during training appears to be associated with cognitive competence in polypectomy in independent practice. These results suggest increasing exposure to EMR in training may improve polypectomy quality amongst practicing endoscopists.

Funding Agencies
CAG
A94 BARRIERS TO ADVANCEMENT ALONG THE GASTROENTEROLOGY CAREER PATHWAY: A RESIDENT PERSPECTIVE
Authors: Pattni C , Jawaid N , Bollegala N 
Published: March 2021

Abstract

Background
GI residency training programs in Canada are comprised of approximately 30% females. Survey data from procedural specialities reveal gender related differences relating to work-life balance, parental obligations, access to role models, and workplace gender discrimination.

Aims
To determine gender specific differences affecting the choice of GI as a sub-specialty and the experience of GI as a career during residency and fellowship.

Methods
A 91-question mixed methods survey was electronically disseminated in two recruitment waves to PGY4-6 gastroenterology residents and fellows across Canada between May 7th-July 1st, 2020. The survey consisted of nine groups of questions aimed at understanding personal, professional, financial, and training characteristics. Comparisons were made between self-identified male and female genders. Wilcoxon (Mann Whitney U test) was used for continuous variables while chi-squared test and fisher’s exact test was applied for categorical variables using SAS software. Qualitative thematic analysis was applied for short answer responses with two independent reviewers.

Results
A total of 122 residents were surveyed with a response rate of 36% (44/122).There were 17 PGY4s, 15 PGY5s, and 12 PGY6s. Females comprised 41% (18/44) of respondents. Women were statistically more likely to take on a predominant caregiver role for children (p=0.012) and state that having children would slow their career advancement (p=0.046). Men were more likely to state that it is preferable to have children during residency (p=0.036) and that their partner’s preference factored into their subspecialty training choice (p=0.009) than women. Male PGY4/5 trainees were more likely to select therapeutic endoscopy for advanced training (p=0.033). No statistical difference was found regarding aspirations for administrative/leadership positions, desired future income, practice setting, academic pursuits, and perspectives on compromising marriage for career. Qualitative analysis suggests non-gender specific challenges related to achieving work-life balance, securing a desired location of practice, and obtaining financial stability are common resident and fellow concerns.

Conclusions
Our study is the first of its kind within the field of gastroenterology to focus on GI residents and fellows’ experiences within Canadian training programs. Our results show that there exist gender related differences in relation to work-life balance and career advancement. Women may benefit from supports to cope with increased caregiver demands in order to allow them to meet career goals which are similar to their male peers.

Funding Agencies
None