慢性炎症:腸における進化(Chronic inflammation: evolution in the gut)

2024-11-262024-12-02

2024-11-25 マックス・プランク研究所

慢性炎症性腸疾患(IBD)の治療において、進化医学の視点が新たなアプローチを提供する可能性があります。進化医学は、進化の過程で人間の生理や免疫系がどのように形成され、現代の疾患に影響を与えているかを研究します。この視点から、IBDの発症や進行に関与する要因を再評価し、より効果的な治療法の開発が期待されています。

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腸の慢性炎症性疾患に対する進化医学: 臨床的ファンタジー以上のもの?
Evolutionary Medicine for Chronic Inflammatory Diseases of the Gut: More Than a Clinical Fantasy?

Nadia Andrea Andreani∗ ∙ Daniel Unterweger∗ ∙ Stefan Schreiber ∙ John F. Baines
Gastroenterology Published:October 17, 2024
DOI:https://doi.org/10.1053/j.gastro.2024.10.016

Figure 1 Bacterial evolution in an inflamed intestine and its clinical relevance. Bacteria in the intestine are exposed to a different environment after the onset of inflammation. Natural selection favors bacterial variants that differ in their genotype from other bacteria in the population and have an increased fitness in the inflamed host environment. Differently colored bacteria depict genetic diversity within the population. Examples for clinically relevant phenotypes of bacteria evolving in an inflamed environment are 1) increased virulence by higher motility and 2) more invasion into host cells. Novel treatment approaches could prevent the evolution of adaptive traits with the use of vitamin B₆ or specifically target evolved bacteria based on their collateral sensitivity to antibiotics.

Evolutionary medicine applies the principles of evolution to improve patient health.¹^,² Several clinical disciplines^3–5 already incorporate evolution, and it has begun to receive attention in gastroenterology.⁶ Four recent experimental studies show evolutionary adaptation of gut bacteria to intestinal inflammation within weeks,^7–10 and an analysis of the intestinal microbiome of patients with inflammatory bowel disease (IBD) identified inflammation-adapted bacterial lineages that evolved over millions of years.¹¹ These findings lay the foundation for evolutionary medicine in patients with chronically inflamed intestines. We see the rise of a new era in gastroenterology therapy with the potential for novel, evolution-informed treatment options ahead.

Changes in an individual’s microbiota can be attributed to bacterial evolution. The human microbiota been subject to macroevolutionary processes on scales of millions of years,¹² and an individual’s lifetime is sufficient for microevolutionary changes in host-associated bacteria, as observed even in healthy volunteers.¹³ The genetic diversity constantly generated by replicating bacteria may give rise to a bacterial variant with a fitness advantage over its ancestor (Figure 1). The variant’s increase in frequency in the bacterial population owing to selection is an example of adaptation by natural selection. Mutations occur both within and between genes, with either direct effects on protein function or on gene expression.