In a recent review published in BJC reports, researchers investigated the complex relationship between gut bacteria, diet, and patient nutrition, aiming to discern how these combined elements impact responses to immune checkpoint inhibitor (ICI) cancer treatment and identify patients most likely to benefit from such therapy.
Study: Gut microbiome and nutrition-related predictors of response to immunotherapy in cancer: making sense of the puzzle. Image Credit: SewCreamStudio/Shutterstock.com
Background
ICI treatment is a groundbreaking anticancer approach that has revolutionized cancer management. It thwarts tumor evasion of immune surveillance, making tumor cells susceptible to the host's immune system.
Predictive tumor biomarkers, like programmed cell death ligand 1 (PD-L1) expression, mutational burden, and microsatellite instability, help identify candidates likely to respond to ICI treatment.
However, overall response rates remain variable across cancer types. The gut microbiome's influence on the host immune system suggests its potential as an efficacy modulator and predictive biomarker for immunotherapy.
While nutrition-related factors, like body weight, impact ICI outcomes, their independent prognostic significance and integration with gut microbiome data for patient selection need further exploration.
Gut bacteria boost the immune system
Human bodies protect against cancer using their immune system, and the bacteria in the gut, known as the gut microbiome, help this process significantly.
For example, mice without these bacteria have fewer immune cells, but adding the bacteria back can fix this. Additionally, gut bacteria help make some cancer drugs more effective.
Role of gut bacteria in ICI cancer treatment
Some gut bacteria help make a cancer treatment like ICI more effective against different cancers. However, taking antibiotics, which can cause dysbiosis in the gut microbiome, might make ICI treatments less effective.
More research is needed to understand the role of specific bacteria in this process.
Cancer's effect on gut bacteria
Cancer patients' gut microbiome differs from those without cancer. For example, certain bacteria like Veillonella are more common in people with untreated lung, pancreatic, and colorectal cancer.
Serious cancer often causes people to eat less due to loss of appetite and side effects from treatment. Changes in eating, bowel movement, and the condition of the intestines can greatly affect the gut microbial composition.
Further, some bacteria are connected to weight loss in cancer patients, suggesting that inflammation might cause changes in how the body uses food. The relationship between gut bacteria and cancer isn't fully understood, but it's clear that cancer affects gut bacteria.
Diet determines microbiome composition
The type of dietary intake greatly affects the kind of bacteria in the gut because these bacteria feed on the food and nutrients in the intestines.
Different foods promote the growth of various bacteria. Dietary modification can cause temporary changes in the gut microbiome composition, but other individual factors also greatly affect how gut bacteria respond to diet.
Body weight, nutrition, and ICI treatment
Weight loss and low body weight often signal worse cancer outcomes. The effect of weight loss on ICI treatment varies between various studies.
A high body mass index (BMI) is associated with better survival rates after ICI treatment in some cancers, but it's unclear how BMI relates to disease-free survival. Body shape, especially muscle mass, is a good indicator of how cancer treatment will go.
People with more subcutaneous (under the skin) fat tend to live longer without disease progression when treated with ICI for various cancers.
However, the type of fat and the state of other tissues may play a role in this. More research is needed to understand this relationship fully.
Using combined factors for better predictions of cancer treatment response
ICI treatment is a powerful weapon against cancer. However, knowing who will respond well to it remains a challenge. Research shows gut bacteria and a patient's nutrition can predict ICI response in lung cancer. Incorporating these factors with existing tumor markers could improve predictions.
Nutritional status could impact the link between gut bacteria and the immune response against cancer. High-tech analysis methods that blend statistics and machine learning can help find the best indicators.
However, the complex relationships between these factors mean changes in one (like body fat) could be offset by others (like gut bacteria). Exploring these combinations may offer insights into improving ICI responses.
Conclusions
Many studies in this review reveal that the individual's gut microbiome profile and nutrition-related characteristics offer extra prognosis information. However, the best method of utilizing these data points to enhance ICI treatment strategies remains unclear.
A blend of statistical modeling and machine-learning techniques, like archetypal analysis, is proposed to identify patterns or feature combinations associated with better post-ICI treatment outcomes.
This strategy for pattern recognition could help highlight important dependencies between nutritional data and gut microbiome, laying the groundwork for potential future interventions to improve treatment results.
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