Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways

Int J Mol Sci. 2021 Aug 31;22(17):9474. doi: 10.3390/ijms22179474.


Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40-100% of patients undergoing chemotherapy, can reduce the patients' quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.

Keywords: chemotherapy; intestinal microbiota dysbiosis; mucositis; toll-like receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Drug Therapy / methods
  • Drug-Related Side Effects and Adverse Reactions / microbiology*
  • Drug-Related Side Effects and Adverse Reactions / physiopathology
  • Dysbiosis / microbiology
  • Dysbiosis / physiopathology
  • Fluorouracil / pharmacology
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology
  • Homeostasis
  • Humans
  • Intestinal Mucosa / microbiology*
  • Intestines / microbiology
  • Microbiota / drug effects
  • Mucositis / chemically induced
  • Quality of Life
  • Signal Transduction / drug effects
  • Toll-Like Receptors / metabolism
  • Toll-Like Receptors / physiology


  • Antineoplastic Agents
  • Toll-Like Receptors
  • Fluorouracil