New therapies could prevent the adjustments in intestinal bacteria that enable them to survive in inflamed regions
New studies suggest that evolutionary medicine could shape the future of gastroenterology. They pave the way for new approaches to treating inflammatory diseases, such as chronic inflammatory bowel diseases.
Will evolution in gut bacteria open roads to healing the gut microbiome?
© Daniela Leitner
Evolutionary medicine examines how evolutionary processes can influence health and disease. Insights from this research could be used to develop innovative approaches to treating chronic inflammatory bowel diseases. Recent studies by members of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” from the Max Planck Institute for Evolutionary Biology in Plön and Kiel University show that an evolutionary perspective has significant potential to expand treatment options for diseases like chronic inflammatory bowel diseases.
In a 2023 study, the research team demonstrated that gut bacteria, such as Escherichia coli, can rapidly adapt to inflammatory environments, becoming more mobile and aggressive. These adaptations enhance the survival and spread of the bacteria in the gut and could play a central role in patients with chronic inflammatory bowel diseases. In a recent review article, which compares this study with other work by international research groups, the researchers further highlight the potential of evolutionary medicine in treating chronic inflammatory diseases.
Rapid adaptation of gut bacteria
The current findings demonstrate how quickly gut bacteria can adapt to inflammatory environments. They change both their genetic makeup and their external characteristics-changes observed in laboratory experiments as well as in patients with chronic inflammatory bowel diseases. A key insight is that certain bacteria, such as Escherichia coli, undergo genetic adaptations when exposed to inflammatory conditions, making them more mobile and aggressive. These changes assist the bacteria in spreading and surviving better in the gut-traits that have also been identified in patients with chronic intestinal inflammation.
Additionally, bacteria develop stress-resistant properties in inflammatory environments, which are enhanced by genetic adaptations. This suggests that inflammation favors bacteria that are more resilient to harsh conditions. “Interestingly, experiments in mice showed that certain nutrients, such as vitamin B6, can prevent harmful bacterial adaptations,” says John Baines, board member of the Cluster of Excellence, head of the “Evolutionary Medicine” research group at the Max Planck Institute for Evolutionary Biology, and professor at Kiel University. In mice harboring inflammation-promoting gut bacteria, the administration of vitamin B6 led to the emergence of less aggressive, stress-resistant bacterial strains. These findings indicate that targeted nutrition could offer a way to control unwanted bacteria.
Another promising approach involves exploiting vulnerabilities that arise from the genetic adaptations of bacteria. Researchers have discovered that while adapted bacteria may thrive better in an inflamed gut, they also become more susceptible to certain antibiotics-a phenomenon known as “collateral sensitivity.” This opens new perspectives for targeted treatments that could alleviate symptoms of chronic inflammatory bowel diseases.
Evolutionarily Informed Strategies
Bacterial evolution in an inflamed intestine: Inflammation promotes genetic variants with higher fitness, such as increased virulence or cell invasion. New therapies could prevent adaptation (e.g., using vitamin B6) or specifically target evolved bacteria with antibiotics.
© John Baines
From the findings of the reviewed studies, researchers from Plön and Kiel have derived novel treatment approaches based on a better understanding of bacterial adaptation mechanisms. Through targeted strategies, it may be possible to prevent or even reverse harmful changes. In addition to the previously mentioned approach-using supplements like vitamin B6 to inhibit unfavorable bacterial adaptations-further innovative concepts are being tested.
One promising method is called Ancestral-State Restorative Therapy. This approach aims to introduce original, non-adapted bacterial strains into the gut to displace harmful, adapted variants. For patients in remission phases-meaning periods during which symptoms have decreased-the approach could offer a natural and safe treatment option.
Moreover, the new insights into bacterial adaptations motivate a reevaluation of existing antibiotics. Therapies specifically targeting bacteria that have adapted to inflammatory conditions could complement conventional treatment approaches and significantly reduce the severity of flare-ups of chronic inflammatory bowel diseases. “Despite promising progress, there are still significant knowledge gaps, particularly regarding the understanding of bacterial evolution in the gut. Previous studies have primarily focused on stool samples, leaving unclear how bacteria behave and adapt in different regions of the gut. Yet these differences are crucial, especially for different subtypes of chronic inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis”, explains John Baines. “Future research should therefore specifically investigate how bacteria develop in various regions of the gut and what role these adaptations play in the different disease forms,” adds Baines. The influence of other microbes, such as fungi and viruses, is also not fully explored and offers promising new avenues for research.
Towards a healthier future
Baines emphasizes: “We see these developments as the beginning of an era in which bacterial evolution in the gut is taken into account, enabling novel, evolutionarily informed therapies.” By applying evolutionary concepts, scientists and physicians hope to develop approaches that not only alleviate the symptoms of chronic inflammatory bowel diseases but also specifically target their causes. Current clinical studies by members of the Cluster of Excellence, such as the administration of vitamin B3 in chronic inflammatory bowel diseases, demonstrate that these innovative concepts have made the leap from the laboratory to clinical testing.
“The insights from evolutionary medicine regarding the adaptation and genetic development of bacteria in the human gut could mark a significant shift in the treatment of chronic inflammatory bowel diseases. With further research, this approach could lay the groundwork for genuine precision medicine, providing personalized, more effective, and sustainable therapies for patients with chronic inflammatory bowel diseases,” says Stefan Schreiber, spokesperson for the Cluster of Excellence, director at the University Hospital Schleswig-Holstein and Kiel University.
