Gut microbiome found to play key role in chronic disease progression

First Hospital of Jilin UniversityNov 15 2024

The gut microbiome, an ecosystem of trillions of microorganisms in the human digestive tract, has been increasingly linked to chronic diseases. Research led by Dr. Connor Prosty and his team at McGill University consolidates recent findings that demonstrate a causal role for the gut microbiome in the progression of multiple diseases, ranging from gastrointestinal conditions to immune-related and psychiatric disorders. Published in eGastroenterology, this narrative review examines how manipulating the gut microbiome may open new therapeutic avenues.

The study draws on recent randomized controlled trials (RCTs) and preclinical evidence that reveal substantial advances in understanding how the gut microbiome affects human health. The most promising findings come from studies on Clostridioides difficile infection (CDI), where fecal microbiota transplantation (FMT)-;a process involving the transfer of stool from a healthy donor into the gastrointestinal tract of a patient-;has shown efficacy in significantly reducing infection recurrence rates. CDI, a severe bacterial infection often triggered by antibiotic use, remains difficult to treat due to its high relapse rate. FMT has emerged as a groundbreaking therapy, with studies showing that it can restore gut microbial balance and reduce recurrence rates by up to 93%.

In addition to CDI, the review highlights the potential role of microbiome-based interventions in cancer immunotherapy and ulcerative colitis (UC). Recent trials suggest that the composition of the gut microbiome may influence how well patients respond to immunotherapy, particularly in cancers such as melanoma and renal cell carcinoma. Findings indicate that individuals with specific gut microbiota profiles, including higher levels of Akkermansia muciniphila and Bifidobacterium, experience better outcomes when undergoing immunotherapy, likely due to the microbiome's role in modulating immune responses. Supplementation with microbiome agents in cancer treatment may thus enhance the body's natural ability to fight tumors.

In UC, a chronic inflammatory condition of the colon, FMT and other microbiome therapies have demonstrated potential as alternatives to conventional, often immunosuppressive treatments. Several trials reveal that FMT can improve symptoms, induce remission, and increase the gut microbial diversity of patients with UC, who typically have less diverse gut bacteria than healthy individuals. This evidence supports the potential of microbiome-altering therapies to modulate the immune response and reduce the need for prolonged use of corticosteroids and other immunosuppressive drugs.

Interestingly, the microbiome's role in obesity is more complex. Although animal studies have shown that changes in gut bacteria can influence weight and metabolic health, RCTs in humans have so far been inconclusive. Trials testing microbiome therapies in patients with obesity and metabolic disorders have not demonstrated significant weight loss or changes in body mass index (BMI), suggesting that while the microbiome plays a role in metabolism, it may not act as a stand-alone solution for weight management.

The review also addresses the challenges and limitations in linking the microbiome to chronic diseases. Factors such as diet, age, and lifestyle contribute to microbiome variability, which can complicate causal analysis. Additionally, differences in microbiome profiles between animal models and humans make it challenging to apply findings directly to human populations. The team suggests that further research is needed to determine the best formulations, dosages, and delivery methods for microbiome therapies, as well as the long-term safety and efficacy of these treatments.

Despite these challenges, Dr. Prosty and his colleagues emphasize the transformative potential of microbiome-targeted therapies.

The gut microbiome is increasingly recognized not only as a biomarker but as a target for therapeutic intervention. These findings validate the microbiome's role in disease development and pave the way for safe, non-invasive treatments that can enhance patient outcomes."

Dr. Connor Prosty, McGill University

With two FDA-approved microbiome therapies already on the market for CDI and multiple ongoing clinical trials exploring microbiome interventions for other conditions, the future of microbiome medicine is promising. Researchers are now focusing on optimizing treatments to ensure patient safety, exploring the impact of diet and lifestyle on microbiome health, and examining how personalized microbiome therapies can be developed to treat or even prevent chronic diseases.

This research positions the gut microbiome as a frontier in healthcare, providing a foundation for therapeutic innovation that could dramatically impact millions of lives worldwide.