Chemotherapy induced gastrointestinal toxicities

Area of Science:

• Gastroenterology and Oncology
• Microbiome Research
• Neurogastroenterology

Background:

• Chemotherapy frequently causes gastrointestinal (GI) dysfunction, including mucositis and diarrhea, impacting treatment adherence and patient safety.
• The rapidly dividing cells of the GI epithelium are a primary target for chemotherapeutic agents, leading to high incidences of toxicity.
• Current treatment options for chemotherapy-induced GI toxicities are limited, often relying on palliative care, highlighting a significant unmet clinical need.

Purpose of the Study:

• To review current knowledge on mechanisms underlying chemotherapy-induced diarrhea and mucositis.
• To explore emerging mechanisms involving the enteric nervous system, smooth muscle, and immune cells in GI toxicity.
• To discuss the role of gut dysbiosis and oxidative stress in chemotherapy-related GI adverse effects and peripheral neuropathy.

Main Methods:

• Literature review synthesizing current understanding of chemotherapy-induced GI toxicities.
• Analysis of emerging mechanisms including the enteric nervous system, immune cells, and gut microbiome.
• Examination of the role of oxidative stress and post-translational modifications in neuronal function.

Main Results:

• Chemotherapy-induced GI toxicity is a prevalent and severe complication, affecting 60%-100% of patients on high-dose regimens.
• Emerging evidence implicates the gut microbiome, enteric nervous system, smooth muscle cells, and immune cells in GI pathogenesis.
• Oxidative stress contributes to altered ion channel function and neuronal excitability, exacerbating GI symptoms.

Conclusions:

• Understanding the interplay between chemotherapy, the gut microbiome, and the enteric nervous system is crucial for developing novel therapeutic strategies.
• Targeting the gut- microbiome axis and oxidative stress pathways offers potential for mitigating severe gastrointestinal toxicities.
• Further research into these mechanisms is essential for discovering new drug targets to improve patient outcomes during chemotherapy.