학술논문
Coordinated elimination of bacterial taxa optimally attenuates alloimmunity and prolongs allograft survival.
Document Type
Academic Journal
Author
Sepulveda M; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Rasic M; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.; Lei YM; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Kwan M; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Chen L; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Chen Y; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.; Perkins D; Department of Nephrology, University of Illinois at Chicago, Chicago, Illinois, USA.; Alegre ML; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA. Electronic address: malegre@uchicago.edu.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 100968638 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-6143 (Electronic) Linking ISSN: 16006135 NLM ISO Abbreviation: Am J Transplant Subsets: MEDLINE
Subject
Language
English
Abstract
This study aimed to dissect the relationship between specific gut commensal bacterial subgroups, their functional metabolic pathways, and their impact on skin allograft outcome and alloimmunity. We previously showed that oral broad-spectrum antibiotic (Abx) pretreatment in mice delayed skin, heart, and lung allograft rejection and dampened alloimmune responses. Here, rationally designed Abx combinations targeting major bacterial groups were used to elucidate their individual contribution to modulating alloimmune responses. Abx cocktails targeting intestinal gram-negative, gram-positive, or anaerobic/gram-positive bacteria by oral gavage, all delayed skin allograft rejection, and reduced alloreactive T cell priming to different extents. Notably, the most pronounced extension of skin allograft survival and attenuation of alloimmunity were achieved when all gut bacterial groups were simultaneously targeted. These results suggest a model in which the strength of the alloimmune response is additively tuned up by gut microbial diversity. Shotgun metagenomic sequencing enabled strain-level resolution and identified a shared commensal, Parabacteroides distasonis, as the most enriched following all Abx treatments. Oral administration of P.distasonis to mice harboring a diverse microbiota significantly prolonged skin allograft survival, identifying a probiotic with therapeutic benefit in transplantation.
Competing Interests: Declaration of competing interest The authors of this manuscript have no conflict of interest to disclose as described by the American Journal of Transplantation. Yuk Man Lei currently holds a position at Exelixis Inc, Alameda, California, USA and Yang Chen currently holds a position at Veracyte, Inc, South San Francisco, California, USA.
(Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors of this manuscript have no conflict of interest to disclose as described by the American Journal of Transplantation. Yuk Man Lei currently holds a position at Exelixis Inc, Alameda, California, USA and Yang Chen currently holds a position at Veracyte, Inc, South San Francisco, California, USA.
(Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)