Evolutionary Medicine: A New Frontier in Treating Chronic Gut Inflammation

Evolutionary medicine, which applies theoretical evolutionary principles to clinical practice, has recently been applied in gastroenterology. New studies highlight the rapid adaptation of gut bacteria to intestinal inflammation, paving the way for novel, evolution-informed treatments for chronic inflammatory gut diseases like IBD.

Bacterial Evolution in the Gut: A Key to Understanding Chronic Inflammation

Changes in the gut microbiota can often be attributed to bacterial evolution. While the human microbiota has undergone macroevolutionary processes over millions of years, microevolutionary changes can occur within an individual's lifetime. This is due to genetic diversity in replicating bacteria, leading to variants with a fitness advantage. This adaptation can increase bacterial virulence and reveal potential therapeutic targets.

Recent studies have demonstrated genotypic and phenotypic changes in bacteria evolving in inflamed environments. These studies reveal common themes regarding bacterial adaptation, despite variations in experimental setups and inflammation triggers. Affected proteins are often involved in stress resistance and motility.

Key findings include:

• Increased Motility and Virulence:E. coli strains adapted to inflamed intestines showed increased motility and invasion into epithelial cells, similar to strains isolated from IBD patients.
• Stress Resistance and Mutation: Bacteria evolving in inflamed guts developed stress resistance and increased mutation rates.
• Vitamin B6 as a Preventative: Vitamin B6 prevented the rise of evolved B. thetaiotaomicron with a specific genetic variant in mice.
• Trade-offs in Adaptation: Adaptation to inflammation can result in sensitivity to certain antibiotics, presenting a therapeutic opportunity.

Implications for Treatment: Novel Targets and Strategies

The pathological relevance of bacterial evolution during inflammation is becoming clearer, with adaptation potentially leading to increased virulence. This knowledge opens doors to novel therapeutic strategies, including:

• Preventing Adaptation: Using interventions like vitamin B6 to prevent bacterial adaptation to inflammation.
• Targeting Adapted Bacteria: Exploiting vulnerabilities, such as antibiotic sensitivity, in inflammation-adapted bacteria.
• Restoring Ancestral State: Utilizing the differential fitness of ancestral bacteria to outcompete evolved strains in a healthier gut environment.

This new research on the intersection of gastroenterology and evolutionary medicine provides important insight into a potential new avenue for treating chronic gut inflammation.

References:

Bäckhed, F, & Elinav, E. Medicine for chronic inflammatory diseases of the gut: More than a clinical fantasy? Gastroenterology, 2025;168(2):439-443. https://doi.org/10.1053/j.gastro.2024.12.016