Research project GUT MICROBES AS MODULATORS OF CHEMOTHERAPY TOXICITY

Gut microbes as a regulator of intestinal recovery

The gut microbiota continuously interacts with cells in the intestinal lining and with immune cells throughout the body. Beneficial microbes produce a wide range of molecules that can influence inflammation, tissue repair, immune-cell development, and metabolic processes. Our previous research has shown that probiotic bacteria such as Limosilactobacillus reuteri and Bifidobacterium longum, as well as bacterial products including extracellular membrane vesicles, can strengthen epithelial barrier function and modulate immune responses (1-2). We recently demonstrated that specific microbial signals may help protect tissues and support recovery following harsh exposures such as chemotherapy (3).

Understanding epithelial repair after chemotherapy

One focus of the project is to understand how the intestinal barrier repairs itself after chemotherapy-induced injury (3). Chemotherapy remains a cornerstone of cancer treatment and has dramatically improved survival rates for many malignancies. However, it also causes substantial collateral damage to the intestinal epithelium, the gut microbiota, and the immune system. Damage to the intestinal epithelium can increase permeability, disrupt tissue homeostasis, and promote inflammation. These effects may persist long after treatment has ended and can contribute to long-term health complications. This is particularly relevant for children and young adults, whose immune system and gut microbiome are still developing.

Using advanced intestinal organoid models and epithelial cell cultures, we investigate how microbial products influence the cellular and molecular pathways involved in tissue regeneration. We are particularly interested in identifying the transcriptional and metabolic programs that enable epithelial cells to recover and restore barrier integrity.

How microbial signals shape immune function

Chemotherapy causes profound changes in immune-cell populations and can result in long-term impairment of immune function. While much is known about its effects on lymphocytes (4-7), far less is understood about how chemotherapy influences innate immune cells such as monocytes and macrophages.

Our research examines how signals originating from damaged intestinal tissue affect immune-cell development and whether beneficial microbes can redirect these responses toward immune regulation rather than excessive inflammation. By studying interactions between epithelial cells, immune cells, and microbial products, we aim to uncover mechanisms that promote long-term immune resilience after treatment.

Immune recovery in children and young adults

To ensure that our findings are clinically relevant, experimental studies are complemented by research involving children and young adults undergoing cancer treatment. We follow changes in immune-cell populations during and after chemotherapy and explore how these changes relate to long-term recovery. By identifying immune signatures associated with successful recovery, we hope to improve our understanding of the long-term consequences of cancer therapy and contribute to better follow-up and supportive care for young cancer survivors