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Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis
Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988921/ https://www.ncbi.nlm.nih.gov/pubmed/35401522 http://dx.doi.org/10.3389/fimmu.2022.737536 |
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author | Ray, Navin Jeong, Hoyoung Kwon, Dasom Kim, Juil Moon, Yuseok |
author_facet | Ray, Navin Jeong, Hoyoung Kwon, Dasom Kim, Juil Moon, Yuseok |
author_sort | Ray, Navin |
collection | PubMed |
description | Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy. Clinical transcriptome dataset-based evaluations demonstrated that levels of dysbiosis-responsive genes were elevated during renal distress, indicating pathological communications between gut and kidney. Experimentally, mucosal exposure to streptomycin aggravated platinum-induced renal tubular lesions in a mouse model. Moreover, antibiotic-induced dysbiosis increased susceptibility to gut mucosal inflammation, epithelial disruption, and bacterial exposure in response to cisplatin treatment. Further investigation of the luminal microbes indicated that antibiotic-induced dysbiosis promoted the dominance of Bacteroides species. Moreover, the functional assessment of dysbiotic microbiota predicted tryptophan metabolic pathways. In particular, dysbiosis-responsive Bacteroides acidifaciens was associated with the production of the uremic toxin indoxyl sulfate and renal injuries. The results of this study including bacterial community-based evaluations provide new predictive insights into the interorgan communications and interventions against dysbiosis-associated disorders. |
format | Online Article Text |
id | pubmed-8988921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89889212022-04-08 Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis Ray, Navin Jeong, Hoyoung Kwon, Dasom Kim, Juil Moon, Yuseok Front Immunol Immunology Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy. Clinical transcriptome dataset-based evaluations demonstrated that levels of dysbiosis-responsive genes were elevated during renal distress, indicating pathological communications between gut and kidney. Experimentally, mucosal exposure to streptomycin aggravated platinum-induced renal tubular lesions in a mouse model. Moreover, antibiotic-induced dysbiosis increased susceptibility to gut mucosal inflammation, epithelial disruption, and bacterial exposure in response to cisplatin treatment. Further investigation of the luminal microbes indicated that antibiotic-induced dysbiosis promoted the dominance of Bacteroides species. Moreover, the functional assessment of dysbiotic microbiota predicted tryptophan metabolic pathways. In particular, dysbiosis-responsive Bacteroides acidifaciens was associated with the production of the uremic toxin indoxyl sulfate and renal injuries. The results of this study including bacterial community-based evaluations provide new predictive insights into the interorgan communications and interventions against dysbiosis-associated disorders. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8988921/ /pubmed/35401522 http://dx.doi.org/10.3389/fimmu.2022.737536 Text en Copyright © 2022 Ray, Jeong, Kwon, Kim and Moon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ray, Navin Jeong, Hoyoung Kwon, Dasom Kim, Juil Moon, Yuseok Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title | Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title_full | Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title_fullStr | Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title_full_unstemmed | Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title_short | Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis |
title_sort | antibiotic exposure aggravates bacteroides-linked uremic toxicity in the gut-kidney axis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988921/ https://www.ncbi.nlm.nih.gov/pubmed/35401522 http://dx.doi.org/10.3389/fimmu.2022.737536 |
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