SYMBIO-THERAPY TARGETING INFLAMMATION AND MICROBIOTA IN ULCERATIVE COLITIS
Résumé
Reciprocal microbiota-host influences constitute the basis for the establishment of a remarkably stable equilibrium in the intestinal ecosystem. We show that this equilibrium can take different forms, representing alternative stable states. A rapid, catastrophic, transition to a different state may be triggered when conditions change beyond a tipping point, and hard or impossible to reverse due to alternative stable state properties. This becomes important when different stable states condition health or chronic diseases like UC: a patient could become “locked” in a disease state.
Our analyses of pediatric UC data show that even after one year of conventional, anti-inflammatory, treatments only 36% of the patients reached a nonpathological host inflammation state, and only about half of these reached the least inflammation-prone microbiota state. The probability of clinical remission depended on the microbiota state before treatment. We postulate that remaining (low level) inflammation or unfavorable microbiota composition may lead to the re-activation of a vicious cycle of microbiota-host interactions and relapse.
We integrated our observations in an innovative conceptual model, which indicates that combined action on inflammation and microbiota (symbio-therapy) should increase chances of restoration of a healthy symbiosis and remission.
We provide the first formal proof for the existence of disease-associated alternative stable states of the human intestinal ecosystem, taking host and microbiota into account. While affecting disease course, knowledge about their behavior opens conceptually new avenues for prevention and therapy. To this end, we propose a fecal sample based non-invasive diagnostic method as an aid in decision making.