Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Haberman, Yael; Tickle, Timothy L.; Dexheimer, Phillip; Kim, Miok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N.; Noe, Joshua D.; Rosh, Joel R.; Markowitz, James; Heyman, Melvin B.; Griffiths, Anne M.; Crandall, Wallace; Mack, David R.; Baker, Susan S.; Huttenhower, Curtis; Keljo, David J.; Hyams, Jeffrey S.; Kugathasan, Subramaniam; Walters, Thomas D.; Aronow, Bruce J.; Xavier, Ramnik J.; Gevers, Dirk; Denson, Lee A.

doi:10.1172/jci75436

Cited by 453 publications

(469 citation statements)

References 47 publications

(68 reference statements)

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“…A previous report by the same group also showed a reduction in F. prausnitzii in patients with Crohn's disease with ileal involvement but not in isolated colonic disease 129. Both the twin study by Willing et al 129 and the large study in children126 and adolescents132 did however show differences between the mucosa-associated microbiota in isolated colonic Crohn's disease and UC. 16sRNA pyrosequencing of mucosal samples131 confirms the increase in E. coli and reduced F. prausnitzii in Crohn's disease with ileal involvement with milder changes in isolated colonic disease, although the latter did show some reduction in F. prausnitzii compared with healthy controls.…”

Section: Microbiotamentioning

confidence: 82%

Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD?

Subramanian

Ekbom

Rhodes

2016

Gut

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Section: Microbiotamentioning

confidence: 82%

Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD?

Subramanian

Ekbom

Rhodes

2016

Gut

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“…Interestingly, in a recent CD patient-based study combining host transcriptomic and microbial profiling, it was found that APOA1 , APOA4 and APOC3 gene expression levels within the CD ileum were downregulated and associated with abundances of specific Firmicutes and Bacteroidetes taxa 55. Although the expression of APOA5 gene was not determined, our results are in line with their findings in that apolipoproteins in the APOA1/C3/A4/A5 gene cluster are associated with specific gut microbial taxa, and that this association is important for gut microbiota-related diseases.…”

Section: Discussionmentioning

confidence: 99%

The effect of heritability and host genetics on the gut microbiota and metabolic syndrome

Lim

You

Yoon

et al. 2016

Gut

295

211

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“… Genes exhibiting upregulation or downregulation in each SILP phagocyte population upon apoptotic IEC sampling were overlapped with IBD susceptibility loci, which were downloaded from the GEO (accession number GSE57945, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57945) 25 . Genes in bold are shared.…”

Section: Figurementioning

confidence: 99%

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs

Cummings

Barbet

Bongers

et al. 2016

Nature

172

214

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Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies1,2. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions3, are not merely extruded to maintain homeostatic cell numbers4, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria5,6. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common ‘suppression of inflammation’ signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease7. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.

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Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Cited by 453 publications

References 47 publications

Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD?

Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD?

The effect of heritability and host genetics on the gut microbiota and metabolic syndrome

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs

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