Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation

Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond...

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Published in:European journal of cancer (1990) 2021-08, Vol.153, p.27-39
Main Authors: Wardill, Hannah R., van der Aa, Stijn A.R., da Silva Ferreira, Ana R., Havinga, Rick, Tissing, Wim J.E., Harmsen, Hermie J.M.
Format: Article
Language:English
Subjects:
Antibiotics
Autografts
Chemotherapy
Complications
Diarrhea
Digestive system
Digestive tract
Disruption
Faecal microbiome transplantation
FMT
Gastrointestinal toxicity
Injury prevention
Intestinal microflora
Methotrexate
Microbiome
Microbiomes
Microbiota
Microenvironments
Microorganisms
Mucosa
Mucosal barrier injury
Mucositis
Toxicity
Transplantation
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container_title European journal of cancer (1990)
container_volume 153
creator Wardill, Hannah R.
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Harmsen, Hermie J.M.
description Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them. Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P 
doi_str_mv 10.1016/j.ejca.2021.05.015
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Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them. Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P &lt; 0.0001) whilst increasing diarrhoea severity (P = 0.0007) and treatment-related mortality (P = 0.0045). 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subjects Antibiotics
Autografts
Chemotherapy
Complications
Diarrhea
Digestive system
Digestive tract
Disruption
Faecal microbiome transplantation
FMT
Gastrointestinal toxicity
Injury prevention
Intestinal microflora
Methotrexate
Microbiome
Microbiomes
Microbiota
Microenvironments
Microorganisms
Mucosa
Mucosal barrier injury
Mucositis
Toxicity
Transplantation
title Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation
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