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The plenary session by Jack Gilbert, PhD, professor of microbial oceanography at the University of California San Diego, focused on translational microbiome therapeutics and their potential applications in various medical conditions, highlighting recent advancements and the importance of microbiome research in clinical practice. While Gilbert’s PhD research focused on ecology in Antarctica, a serendipitous email from a surgeon motivated him to understand the relationship between the human microbiome and health ─ and apply that knowledge on a clinical scale.
In his talk, Gilbert emphasized his concept of 3 Ms: mechanisms, metrics, and modifiers. He discussed how understanding the microbiome’s influence on health can lead to better diagnostics, treatments, and modifications for depression, cardiometabolic health, and colorectal cancer, among other conditions. He also addressed the complexity of the microbiome and its potential for diagnostics driven by artificial intelligence (AI) and personalized medicine.
Gilbert discussed the challenges of applying ecological principles to clinical practice, particularly in the field of microbiome research. As he explained, a microbial enzyme can exacerbate the risk of colorectal cancer recurrence after surgery, whereas traditional treatments like antibiotics are ineffective on those microbes, making it difficult to address these complex issues in clinical settings.
He presented studies on collagenolytic bacteria, which have been linked to an increase in the risk of surgery-associated cancer in individuals with obesity and those who consume Western diets. Other ongoing studies are investigating the impact of removing collagenolytic bacteria with diet in patients with serrated polyposis syndrome.
Using microbiome metrics can help with diagnosing diseases as well as predicting disease risk and treatment responses. For instance, the skin microbiome impacts surgical site infections, while oral bacteria in the gut can help predict inflammatory bowel disease and colorectal cancer.
A large microbiome study found that residents of Ghana have higher alpha microbial diversity than people in the United States — which is likely due to the high fiber content in Ghanian diets. Alpha diversity in microbiomes is positively correlated with short-chain fatty-acid concentrations in feces and thus a reduction in metabolic-disease risk.
Specific microbiomes can be used to modify therapies. For example, fecal microbial transplants can enhance the efficacy of immunotherapy for cancers and improve general immune and gut health. Phage therapies are currently under investigation for cystic fibrosis patients with infections.
Gilbert uses multi-“omic” approaches in microbiome studies, including metagenomics, metatranscriptomics, metaproteomics, and metabolomics. He also integrates AI to create a comprehensive picture of microbial and molecular activity. He described a device called GutLab developed by Biome Sense, which allows for the continuous, noninvasive collection of stool samples with high reproducibility and efficiency.
Additionally, he emphasized the importance of developing diagnostic biomarkers, which have the potential to reduce bias and costs while increasing reliability through the integration of robotics and standardized assays.
Despite the need for more diverse research, significant progress is being made in developing diagnostic tools and microbiome-based therapies. Two FDA-approved microbiome therapeutics are currently available for C. diff (Clostridioides difficile), and several ongoing clinical trials are under way for various indications, including fatty liver and kidney diseases, according to Gilbert. Predicting disease risk or treatment response is the future of precision microbiome medicine!
