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Title: Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis

Abstract

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin 15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and play a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). While the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S rRNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (v-IL-15tg mice) shows distinct changes in the composition of the intestinal bacteria. While some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum, and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota inducedmore » by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.« less

Authors:
; ; ; ; ; ; ; ORCiD logo; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
University of Chicago; National Institutes of Health (NIH)
OSTI Identifier:
1429905
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
The ISME Journal
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 1751-7362
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
autoimmunity; butyrate; dysbiosis; dysbiosis, interleukin-15, butyrate, inflammatory bowel disease, autoimmunity; inflammatory bowel disease; interleukin-­15

Citation Formats

Meisel, Marlies, Mayassi, Toufic, Fehlner-Peach, Hannah, Koval, Jason C., O'Brien, Sarah L., Hinterleitner, Reinhard, Lesko, Kathryn, Kim, Sangman, Bouziat, Romain, Chen, Li, Weber, Christopher R., Mazmanian, Sarkis K., Jabri, Bana, and Antonopoulos, Dionysios A. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis. United States: N. p., 2016. Web. doi:10.1038/ismej.2016.114.
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Meisel, Marlies, Mayassi, Toufic, Fehlner-Peach, Hannah, Koval, Jason C., O'Brien, Sarah L., Hinterleitner, Reinhard, Lesko, Kathryn, Kim, Sangman, Bouziat, Romain, Chen, Li, Weber, Christopher R., Mazmanian, Sarkis K., Jabri, Bana, & Antonopoulos, Dionysios A. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis. United States. doi:10.1038/ismej.2016.114.
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Meisel, Marlies, Mayassi, Toufic, Fehlner-Peach, Hannah, Koval, Jason C., O'Brien, Sarah L., Hinterleitner, Reinhard, Lesko, Kathryn, Kim, Sangman, Bouziat, Romain, Chen, Li, Weber, Christopher R., Mazmanian, Sarkis K., Jabri, Bana, and Antonopoulos, Dionysios A. Tue . "Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis". United States. doi:10.1038/ismej.2016.114.
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@article{osti_1429905,
title = {Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis},
author = {Meisel, Marlies and Mayassi, Toufic and Fehlner-Peach, Hannah and Koval, Jason C. and O'Brien, Sarah L. and Hinterleitner, Reinhard and Lesko, Kathryn and Kim, Sangman and Bouziat, Romain and Chen, Li and Weber, Christopher R. and Mazmanian, Sarkis K. and Jabri, Bana and Antonopoulos, Dionysios A.},
abstractNote = {Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin 15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and play a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). While the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S rRNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (v-IL-15tg mice) shows distinct changes in the composition of the intestinal bacteria. While some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum, and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.},
doi = {10.1038/ismej.2016.114},
journal = {The ISME Journal},
issn = {1751-7362},
number = 1,
volume = 11,
place = {United States},
year = {2016},
month = {9}
}
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Journal Article:
DOI:  10.1038/ismej.2016.114
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