Sunday 12 May 2024

The Role of Microbiome Research in Personalized Medicine


Image designed by Tim Sandle

The human microbiome contains trillions of microorganisms from thousands of species. Researchers still have a lot to learn, but they know aspects such as a person’s diet, environment and DNA can influence the body’s microbiota. Further work in this area could result in pharmaceutical companies making individualized drugs for specific patients rather than using mass-market approaches. What progress has happened so far?


By Emily Newton


Finding a Colorectal Cancer Connection

Mutated genes occur in 60% of colorectal patients, with over 20% of TP53-mutated tumor cases linked to shorter survival periods and more aggressive disease forms. Researchers have also learned that such mutations can disrupt the gut microbiome. Recently, a group made another valuable discovery that could further personalize medicine.


The team identified microbiota signatures associated with colorectal cancer and those mutations, believing the gut could contain non-invasive biomarkers identifying disease subtypes. Studying those might reveal new findings to support diagnostic methods and a clearer understanding of patients’ cancer progression.


The researchers used 16s rRNA sequencing to examine stool samples from 94 patients with colorectal cancer. Their approach revealed 24 samples containing the specific mutation — the rest had the non-mutated gene. The mutant sample group also had 24 gut microbiota types not present in the other specimens, while three were categorized as non-invasive colorectal cancer biomarkers.


Experts found that the non-mutated samples contained two microbes linked to probiotic activity. Although they will need to investigate further with a larger patient cohort, the team believed those two bacteria types could reduce a patient’s likelihood of developing the genetic mutation in their tumors. Such outcomes could support learning more about the disease’s progression and tailored treatments.

Improving Patients’ Response to Treatments

Some precision medicinal work has examined patient response to particular treatments, which could significantly reduce severe side effects or ineffective therapies. The information could also tell medical practitioners what preliminary steps to take so that interventions get the best results.


Specialized equipment has undoubtedly spurred microbiome research. Some types can show high-resolution images of specimens as thin as 1 nanometer in width, helping scientists observe on the molecular level. Such advancements also support large-scale studies featuring data collected from multiple locations.


In one 2022 study, researchers gathered biome data from five sites in three countries to learn about patient responses to melanoma treatments. The results showed that patients with three specific bacteria types in their guts responded better to immunotherapy than those without.


The experts also discovered potential links between external factors like patients’ diets, proton pump inhibitors and the microbiome makeup. The team eventually hopes to determine which microbiome characteristics most impact immunotherapy responses. Capitalizing on those could enable pharmaceutical companies to create personalized treatments.


This study reinforces the importance of gut health and a good diet, as the researchers determined patients who had both were nearly 50% as likely to survive after five years. This outcome could also encourage doctors to prescribe dietary changes or probiotic supplements before patients’ treatments.

Developing a Microbiome Research Approach

Scientists have become more interested in metabolomics, the study of a system’s small molecules. As they learn more about molecular interactions with human cells, the takeaways could influence the future of microbiome research. However, metabolomic studies can usually only characterize about 10% of the molecular microbiome data from each sample.


In December 2023, a team of microbiome experts introduced a pioneering approach they call “reverse metabolomics,” which provides an improved understanding of the microbiome’s impact on human health. This new approach combines data science, mass spectrometry and organic synthesis.


The team’s first application of their method allowed them to observe hundreds of molecules for the first time. They used those insights to identify a new metabolomic signature associated with inflammatory bowel disease, believing it could improve diagnostics and treatments for people with the condition.


Reverse metabolomics allows for checking samples for specific molecules and predicting which microbes produce them. These findings facilitate efforts to find links between health and disease.


In one example, the team examined a synthesized class of microbial molecules called bile amidates and found potential inflammatory bowel disease markers across multiple cohorts. However, some variations existed.


For example, active Crohn’s disease symptoms caused specific bile amidate elevations in patients, but researchers did not see the same results in those with ulcerative colitis. Additional experiments suggested several bile amide compounds could disrupt T-cell function and inflame the gut. 


Once scientists learn more about such patterns, they can use them to diagnose specific medical issues and customize treatments. These researchers envision a future where patients receive live microbe-containing pills that secrete particular molecules. Alternatively, new drugs could work by inhibiting the enzymes associated with disease-linked molecular interactions.

A Fascinating Time for Personalized Medicine

Although researchers are in the early stages of understanding the human microbiome, these examples show significant improvements. As such innovations progress, patients can look forward to instances where they get tailor-made medicine for their specific symptoms and conditions. Such interventions could dramatically enhance their quality of life and reduce the likelihood of disease complications resulting in hospitalizations or emergency care.


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