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Article: Co-Development of Three Dietary Indices to Facilitate Dietary Intake Assessment of Pediatric Crohn's Disease Patients.

Harvey, Antonia / Mannette, Jessica / Sigall-Boneh, Rotem / Macintyre, Brad / Parrott, Matthew / Cahill, Leah / Connors, Jessica / Otley, Anthony / Haskett, Jennifer / van Limbergen, Johan / Grant, Shannan

Canadian journal of dietetic practice and research : a publication of Dietitians of Canada = Revue canadienne de la pratique et de la recherche en dietetique : une publication des Dietetistes du Canada

2024 , Page(s) 1–8

Abstract: Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric ... ...

Abstract	Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (
Language	English
Publishing date	2024-04-18
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1472222-7
ISSN	1486-3847
ISSN	1486-3847
DOI	10.3148/cjdpr-2024-005
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Article: The Role of Succinate in the Regulation of Intestinal Inflammation

Connors, Jessica / Dawe, Nick / Van Limbergen, Johan

Nutrients. 2018 Dec. 22, v. 11, no. 1

2018

Abstract: Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle within host cells. Succinate is also produced in large amounts during bacterial fermentation of dietary fiber. Elevated succinate levels within the gut lumen have been reported ... ...

Abstract	Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle within host cells. Succinate is also produced in large amounts during bacterial fermentation of dietary fiber. Elevated succinate levels within the gut lumen have been reported in association with microbiome disturbances (dysbiosis), as well as in patients with inflammatory bowel disease (IBD) and animal models of intestinal inflammation. Recent studies indicate that succinate can activate immune cells via its specific surface receptor, succinate receptor 1(SUCNR1), and enhance inflammation. However, the role of succinate in inflammatory processes within the gut mucosal immune system is unclear. This review includes current literature on the association of succinate with intestinal inflammation and the potential role of succinate–SUCNR1 signaling in gut immune functions.
Keywords	animal models ; dietary fiber ; dysbiosis ; fermentation ; immune response ; immune system ; inflammation ; inflammatory bowel disease ; intestines ; microbiome ; mucosal immunity ; patients ; tricarboxylic acid cycle
Language	English
Dates of publication	2018-1222
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu11010025
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Role of Succinate in the Regulation of Intestinal Inflammation.

Connors, Jessica / Dawe, Nick / Van Limbergen, Johan

Nutrients

2018 Volume 11, Issue 1

Abstract	Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle within host cells. Succinate is also produced in large amounts during bacterial fermentation of dietary fiber. Elevated succinate levels within the gut lumen have been reported in association with microbiome disturbances (dysbiosis), as well as in patients with inflammatory bowel disease (IBD) and animal models of intestinal inflammation. Recent studies indicate that succinate can activate immune cells via its specific surface receptor, succinate receptor 1(SUCNR1), and enhance inflammation. However, the role of succinate in inflammatory processes within the gut mucosal immune system is unclear. This review includes current literature on the association of succinate with intestinal inflammation and the potential role of succinate⁻SUCNR1 signaling in gut immune functions.
MeSH term(s)	Animals ; Bacteria/metabolism ; Dysbiosis ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/physiology ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/physiology ; Inflammatory Bowel Diseases ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; Intestines/immunology ; Intestines/microbiology ; Receptors, G-Protein-Coupled/physiology ; Signal Transduction/physiology ; Succinic Acid/metabolism ; Succinic Acid/pharmacology
Chemical Substances	Receptors, G-Protein-Coupled ; Succinic Acid (AB6MNQ6J6L)
Language	English
Publishing date	2018-12-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu11010025
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Article: Opinion: Are Organoids the End of Model Evolution for Studying Host Intestinal Epithelium/Microbe Interactions?

George, Michelle M / Rahman, Mushfiqur / Connors, Jessica / Stadnyk, Andrew W

Microorganisms

2019 Volume 7, Issue 10

Abstract: In the pursuit to understand intestinal epithelial cell biology in health and disease, researchers have established various model systems, from whole animals (typically rodents) with experimentally induced disease to transformed human carcinomas. The ... ...

Abstract	In the pursuit to understand intestinal epithelial cell biology in health and disease, researchers have established various model systems, from whole animals (typically rodents) with experimentally induced disease to transformed human carcinomas. The obvious limitation to the ex vivo or in vitro cell systems was enriching, maintaining, and expanding differentiated intestinal epithelial cell types. The popular concession was human and rodent transformed cells of mainly undifferentiated cells, with a few select lines differentiating along the path to becoming goblet cells. Paneth cells, in particular, remained unculturable. The breakthrough came in the last decade with the report of conditions to grow mouse intestinal organoids. Organoids are 3-dimensional ex vivo "mini-organs" of the organ from which the stem cells were derived. Intestinal organoids contain fully differentiated epithelial cells in the same spatial organization as in the native epithelium. The cells are suitably polarized and produce and secrete mucus onto the apical surface. This review introduces intestinal organoids and provide some thoughts on strengths and weaknesses in the application of organoids to further advance our understanding of the intestinal epithelial-microbe relationship.
Language	English
Publishing date	2019-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms7100406
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Article: Opinion: Are Organoids the End of Model Evolution for Studying Host Intestinal Epithelium/Microbe Interactions?

George, Michelle M / Rahman, Mushfiqur / Connors, Jessica / Stadnyk, Andrew W

Microorganisms. 2019 Sept. 29, v. 7, no. 10

2019

Abstract	In the pursuit to understand intestinal epithelial cell biology in health and disease, researchers have established various model systems, from whole animals (typically rodents) with experimentally induced disease to transformed human carcinomas. The obvious limitation to the ex vivo or in vitro cell systems was enriching, maintaining, and expanding differentiated intestinal epithelial cell types. The popular concession was human and rodent transformed cells of mainly undifferentiated cells, with a few select lines differentiating along the path to becoming goblet cells. Paneth cells, in particular, remained unculturable. The breakthrough came in the last decade with the report of conditions to grow mouse intestinal organoids. Organoids are 3-dimensional ex vivo “mini-organs” of the organ from which the stem cells were derived. Intestinal organoids contain fully differentiated epithelial cells in the same spatial organization as in the native epithelium. The cells are suitably polarized and produce and secrete mucus onto the apical surface. This review introduces intestinal organoids and provide some thoughts on strengths and weaknesses in the application of organoids to further advance our understanding of the intestinal epithelial–microbe relationship.
Keywords	carcinoma ; goblet cells ; humans ; intestinal mucosa ; mice ; models ; mucus ; stem cells
Language	English
Dates of publication	2019-0929
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms7100406
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Bacterial Taxa and Functions Are Predictive of Sustained Remission Following Exclusive Enteral Nutrition in Pediatric Crohn's Disease.

Jones, Casey M A / Connors, Jessica / Dunn, Katherine A / Bielawski, Joseph P / Comeau, André M / Langille, Morgan G I / Van Limbergen, Johan

Inflammatory bowel diseases

2020 Volume 26, Issue 7, Page(s) 1026–1037

Abstract: Background: The gut microbiome is extensively involved in induction of remission in pediatric Crohn's disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ ... ...

Abstract	Background: The gut microbiome is extensively involved in induction of remission in pediatric Crohn's disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks. Methods: A total of 139 fecal samples were obtained from 22 patients (8-15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn's Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels. Results: Microbial diversity did not change after EEN, but species richness was lower in low-FCP samples (<250 µg/g). An RF model using microbial abundances, species richness, and Paris disease classification was the best at classifying treatment response (area under the curve [AUC] = 0.9). KEGG Pathways also significantly classified treatment response with the addition of the same clinical data (AUC = 0.8). Top features of the RF model are consistent with previously identified IBD taxa, such as Ruminococcaceae and Ruminococcus gnavus. Conclusions: Our machine learning approach is able to distinguish SR and non-SR samples using baseline microbiome and clinical data.
MeSH term(s)	Adolescent ; Bacteria/classification ; Bacteria/genetics ; Bacterial Typing Techniques/methods ; Bacterial Typing Techniques/statistics & numerical data ; Child ; Crohn Disease/microbiology ; Crohn Disease/therapy ; Enteral Nutrition ; Feces/chemistry ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/genetics ; Humans ; Leukocyte L1 Antigen Complex/analysis ; Machine Learning ; Male ; Metagenome ; Predictive Value of Tests ; Prospective Studies ; RNA, Ribosomal, 16S ; Recurrence ; Remission Induction ; Severity of Illness Index
Chemical Substances	Leukocyte L1 Antigen Complex ; RNA, Ribosomal, 16S
Language	English
Publishing date	2020-01-20
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1340971-2
ISSN	1536-4844 ; 1078-0998
ISSN (online)	1536-4844
ISSN	1078-0998
DOI	10.1093/ibd/izaa001
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Article ; Online: Infectious Complications Are Associated With Alterations in the Gut Microbiome in Pediatric Patients With Acute Lymphoblastic Leukemia.

Nearing, Jacob T / Connors, Jessica / Whitehouse, Scott / Van Limbergen, Johan / Macdonald, Tamara / Kulkarni, Ketan / Langille, Morgan G I

Frontiers in cellular and infection microbiology

2019 Volume 9, Page(s) 28

Abstract: Acute lymphoblastic leukemia is the most common pediatric cancer. Fortunately, survival rates exceed 90%, however, infectious complications remain a significant issue that can cause reductions in the quality of life and prognosis of patients. Recently, ... ...

Abstract	Acute lymphoblastic leukemia is the most common pediatric cancer. Fortunately, survival rates exceed 90%, however, infectious complications remain a significant issue that can cause reductions in the quality of life and prognosis of patients. Recently, numerous studies have linked shifts in the gut microbiome composition to infection events in various hematological malignances including acute lymphoblastic leukemia (ALL). These studies have been limited to observing broad taxonomic changes using 16S rRNA gene profiling, while missing possible differences within microbial functions encoded by individual species. In this study we present the first combined 16S rRNA gene and metagenomic shotgun sequencing study on the gut microbiome of an independent pediatric ALL cohort during treatment. In this study we found distinctive differences in alpha diversity and beta diversity in samples from patients with infectious complications in the first 6 months of therapy. We were also able to find specific species and functional pathways that were significantly different in relative abundance between samples that came from patients with infectious complications. Finally, machine learning models based on patient metadata and bacterial species were able to classify samples with high accuracy (84.09%), with bacterial species being the most important classifying features. This study strengthens our understanding of the association between infection and pediatric acute lymphoblastic leukemia treatment and warrants further investigation in the future.
MeSH term(s)	Child ; Child, Preschool ; Cluster Analysis ; DNA, Ribosomal/chemistry ; DNA, Ribosomal/genetics ; Dysbiosis/complications ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Male ; Metagenomics ; Microbiota ; Opportunistic Infections/microbiology ; Phylogeny ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA
Chemical Substances	DNA, Ribosomal ; RNA, Ribosomal, 16S
Language	English
Publishing date	2019-02-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2019.00028
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Article ; Online: The relationship between fecal bile acids and microbiome community structure in pediatric Crohn's disease.

Connors, Jessica / Dunn, Katherine A / Allott, Jennifer / Bandsma, Robert / Rashid, Mohsin / Otley, Anthony R / Bielawski, Joseph P / Van Limbergen, Johan

The ISME journal

2019 Volume 14, Issue 3, Page(s) 702–713

Abstract: Gut microbiome community structure is associated with Crohn's disease (CD) development and response to therapy. Bile acids (BAs) play a central role in modulating intestinal immune responses, and changes in gut bacterial communities can profoundly alter ... ...

Abstract	Gut microbiome community structure is associated with Crohn's disease (CD) development and response to therapy. Bile acids (BAs) play a central role in modulating intestinal immune responses, and changes in gut bacterial communities can profoundly alter the intestinal BA pool. The liver synthesizes and conjugates primary bile acids (priBAs) that are then deconjugated, epimerized, and dehydroxylated by gut bacteria to produce secondary bile acids (secBAs). We investigated the relationship between the gut microbiome and the fecal BA pool in stool samples obtained from a well-characterized cohort of pediatric CD patients undergoing nutritional therapy to induce disease remission. We found that fecal BA composition was altered in a sub-group of CD patients who did not sustain remission. The microbial community structures associated with priBA and secBA-dominant profiles were distinct. In addition, the fecal BA concentrations were correlated with the abundance of distinct bacterial taxonomic groups. Finally, priBA dominant samples were associated with community-level decreases in enzymes for dehydroxylation but not deconjugation.
MeSH term(s)	Adolescent ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; Bile Acids and Salts/metabolism ; Child ; Crohn Disease/metabolism ; Crohn Disease/microbiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/microbiology ; Liver/metabolism ; Male
Chemical Substances	Bile Acids and Salts
Language	English
Publishing date	2019-12-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2406536-5
ISSN	1751-7370 ; 1751-7362
ISSN (online)	1751-7370
ISSN	1751-7362
DOI	10.1038/s41396-019-0560-3
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Article ; Online: Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia.

Dunn, Katherine A / Forbrigger, Zara / Connors, Jessica / Rahman, Mushfiqur / Cohen, Alejandro / Van Limbergen, Johan / Langille, Morgan G I / Stadnyk, Andrew W / Bielawski, Joseph P / Penny, Susanne L / MacDonald, Tamara / Kulkarni, Ketan

Leukemia & lymphoma

2021 Volume 62, Issue 13, Page(s) 3244–3255

Abstract: Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine, consequentially affecting aspartate, glutamine and glutamate. The gut as a confounding source of ... ...

Abstract	Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine, consequentially affecting aspartate, glutamine and glutamate. The gut as a confounding source of these amino acids (AAs) and the role of gut microbiome metabolism of AAs has not been examined. We examined asparagine, aspartate, glutamine and glutamate in stool samples from patients over pegaspargase treatment. Microbial gene-products, which interact with these AAs were identified. Stool asparagine declined significantly, and 31 microbial genes changed over treatment. Changes were complex, and included genes involved in AA metabolism, nutrient sensing, and pathways increased in cancers. While we identified changes in a gene (
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Asparaginase/adverse effects ; Asparagine ; Aspartic Acid ; Child ; Genes, Bacterial ; Glutamic Acid/therapeutic use ; Glutamine/therapeutic use ; Humans ; Polyethylene Glycols/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Chemical Substances	Antineoplastic Agents ; Glutamine (0RH81L854J) ; Aspartic Acid (30KYC7MIAI) ; Glutamic Acid (3KX376GY7L) ; Polyethylene Glycols (3WJQ0SDW1A) ; Asparagine (7006-34-0) ; pegaspargase (7D96IR0PPM) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2021.1953006
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Zs.A 2997: Show issues

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Article: The Impact of Exclusive Enteral Nutrition (EEN) on the Gut Microbiome in Crohn’s Disease: A Review

MacLellan, Amber / Connors, Jessica / Grant, Shannan / Cahill, Leah / Langille, Morgan G. I / Van Limbergen, Johan

Nutrients. 2017 May 01, v. 9, no. 5

2017

Abstract: Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is thought to arise from a complex interaction of genetics, the gut microbiome, and environmental factors, such as diet. There is clear evidence that dietary intervention is successful in ... ...

Abstract	Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is thought to arise from a complex interaction of genetics, the gut microbiome, and environmental factors, such as diet. There is clear evidence that dietary intervention is successful in the treatment of CD—exclusive enteral nutrition (EEN) is able to induce remission in up to 80% of CD patients. While the mechanism of action of EEN is not clear, EEN is known to cause profound changes in the gut microbiome. Understanding how EEN modifies the gut microbiome to induce remission could provide insight into CD etiopathogenesis and aid the development of microbiome-targeted interventions to guide ongoing dietary therapy to sustain remission. This review includes current literature on changes in composition and function of the gut microbiome associated with EEN treatment in CD patients.
Keywords	Crohn disease ; diet ; enteral feeding ; environmental factors ; genetics ; intestinal microorganisms ; mechanism of action ; nutritional intervention ; patients ; remission
Language	English
Dates of publication	2017-0501
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu9050447
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