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Microbiome. 2021 Nov 03;9(1):215. doi: 10.1186/s40168-021-01161-3.

Utilizing a reductionist model to study host-microbe interactions in intestinal inflammation.

Microbiome

Amy M Tsou, Jeremy A Goettel, Bin Bao, Amlan Biswas, Yu Hui Kang, Naresh S Redhu, Kaiyue Peng, Gregory G Putzel, Jeffrey Saltzman, Ryan Kelly, Jordan Gringauz, Jared Barends, Mai Hatazaki, Sandra M Frei, Rohini Emani, Ying Huang, Zeli Shen, James G Fox, Jonathan N Glickman, Bruce H Horwitz, Scott B Snapper

Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. [email protected].
  2. Harvard Medical School, Boston, MA, USA. [email protected].
  3. Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, NY, USA. [email protected].
  4. Division of Pediatric Gastroenterology and Nutrition, Weill Cornell Medical College, New York, NY, USA. [email protected].
  5. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
  6. Harvard Medical School, Boston, MA, USA.
  7. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  8. Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China.
  9. Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, NY, USA.
  10. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
  11. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  12. Division of Emergency Medicine, Boston Children's Hospital, Boston, MA, USA.
  13. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. [email protected].
  14. Harvard Medical School, Boston, MA, USA. [email protected].
  15. Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA. [email protected].

PMID: 34732258 PMCID: PMC8565002 DOI: 10.1186/s40168-021-01161-3

Abstract

BACKGROUND: The gut microbiome is altered in patients with inflammatory bowel disease, yet how these alterations contribute to intestinal inflammation is poorly understood. Murine models have demonstrated the importance of the microbiome in colitis since colitis fails to develop in many genetically susceptible animal models when re-derived into germ-free environments. We have previously shown that Wiskott-Aldrich syndrome protein (WASP)-deficient mice (Was

RESULTS: Was

CONCLUSIONS: These studies indicate that the effect of a microbe on the immune system can be context dependent, with the same bacteria eliciting a tolerogenic response under homeostatic conditions but promoting inflammation in immune-dysregulated hosts. Furthermore, in inflamed environments, some bacteria up-regulate genes that enhance their fitness and immunogenicity, while other bacteria are less able to adapt and decrease in abundance. These findings highlight the importance of studying host-microbe interactions in different contexts and considering how the transcriptional profile and fitness of bacteria may change in different hosts when developing microbiota-based therapeutics. Video abstract.

© 2021. The Author(s).

Keywords: Defined consortium; Gut microbiota; Immune dysregulation; Intestinal inflammation; Pathobiont; Wiskott-Aldrich syndrome

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