Microbiota modulate Doxorubicin induced cardiotoxicity.

Area of Science:

• Cardiology
• Microbiology
• Toxicology

Background:

• Chemotherapy, like Doxorubicin, can cause life-threatening adverse effects.
• Doxorubicin-induced cardiac dysfunction is a significant clinical concern.
• The role of gut microbiome imbalance and intestinal damage in Doxorubicin's cardiotoxicity is under investigation.

Purpose of the Study:

• To investigate the hypothesis that Doxorubicin-induced microbiome imbalance and intestinal damage contribute to cardiac dysfunction.
• To evaluate the therapeutic potential of fecal microbiota transplantation (FMT) in mitigating Doxorubicin's cardiotoxic effects.

Main Methods:

• Mice were administered varying doses of Doxorubicin.
• Cardiac function was assessed using echocardiography.
• Gut microbiome composition was analyzed via 16S rRNA sequencing.
• Fecal microbiota transplantation (FMT) was performed to assess its impact on Doxorubicin-induced toxicity.

Main Results:

• Doxorubicin induced a dose-dependent increase in mortality and cardiac dysfunction.
• A 5 mg/kg dose of Doxorubicin significantly impaired cardiac function (reduced LVEF and FS), increased cardiac fibrosis, inflammation, and oxidative stress.
• This dose also caused significant intestinal damage, including reduced colorectum length, goblet cell loss, ulcers, decreased ZO-1 expression, and increased plasma endotoxin.
• 16S rRNA analysis revealed Doxorubicin-induced gut dysbiosis with reduced microbial diversity.
• FMT significantly improved cardiac function, reduced cardiac fibrosis, ameliorated intestinal damage, and restored gut microbiota composition and diversity.

Conclusions:

• Doxorubicin-induced cardiac dysfunction is associated with gut microbiome imbalance and intestinal damage.
• Fecal microbiota transplantation (FMT) can effectively improve cardiac function and mitigate Doxorubicin-induced cardiotoxicity and gut injury.
• The gut microbiota plays a crucial role in the heart-gut interaction and Doxorubicin's adverse effects.