PhD Scientific Days 2024

Theoretical and Translational Medicine II.

The role of dietary interventions associated microbiome changes and immunotherapy outcomes

Text of the abstract

Introduction
In recent years, cancer patients' survival has shown gradual enhancement due to immune checkpoint inhibitors (ICIs). Several studies have brought to light a notable association between the intestinal microbiome and ICI efficacy. Strategies for modifying the composition of the gut microbiome encompass various types of dietary interventions, which can have varied impacts on the outcomes of ICI-treated patients.
Aims
Our aim was to validate the beneficial effect of dietary intervention on intestinal microbiome and ICI efficacy.
Methods
The outcomes in the observed studies were overall response rate or overall survival in the human studies, and tumor size change in mouse studies. The comparator attributions were dietary interventions, including high fiber, sugar, protein intake, and fasting. Nineteen articles (6 human and 12 mouse studies) met the inclusion criteria, and were marked as eligible for the review.
Results
Human data shows that high fiber intake is associated with ICI efficacy as well as low sugar consumption. In mice, limited accessibility of certain amino acids like Met, and low amounts of Leu and Gln favor cancer progression. Intermittent fasting and fast-mimicking diet also affect treatment efficacy beneficially. In humans, a high relative abundance of short-chain fatty acid (SCFA), and lactic acid producers correlated with good ICI response, as well as the presence of Faecalibacterium prausnitzii and Akkermansia muciniphilia. This was confirmed in mouse models regarding increased levels of SCFA and lactic acid producers, showing that dietary restrictions might affect the composition of intestinal microbiome, and their metabolic potential. Mouse studies highlight the direct, causal connection between dietary fiber intake and greater microbial diversity, as well as the presence of fermentative bacteria, which is assumed by human studies.
Conclusion
The alterations in microbiota composition linked to diet, observed in human research, appear to be confirmed in animal models, particularly regarding the production of SCFAs and lactic acid, as well as modifications in the overall diversity of microbial populations.
Funding
Hungarian National Research, Development and Innovation Office ((#146775)