School of Plant Sciences and Food Security, Tel Aviv University, Tel Aviv, 6997801, Israel.
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Commun Biol. 2023 Jul 26;6(1):782. doi: 10.1038/s42003-023-05099-0.
Recent studies revealed mechanisms by which the microbiome affects its host's brain, behavior and wellbeing, and that dysbiosis - persistent microbiome-imbalance - is associated with the onset and progress of various chronic diseases, including addictive behaviors. Yet, understanding of the ecological and evolutionary processes that shape the host-microbiome ecosystem and affect the host state, is still limited. Here we propose that competition dynamics within the microbiome, associated with host-microbiome mutual regulation, may promote dysbiosis and aggravate addictive behaviors. We construct a mathematical framework, modeling the dynamics of the host-microbiome ecosystem in response to alterations. We find that when this ecosystem is exposed to substantial perturbations, the microbiome may shift towards a composition that reinforces the new host state. Such a positive feedback loop augments post-perturbation imbalances, hindering attempts to return to the initial equilibrium, promoting relapse episodes and prolonging addictions. We show that the initial microbiome composition is a key factor: a diverse microbiome enhances the ecosystem's resilience, whereas lower microbiome diversity is more prone to lead to dysbiosis, exacerbating addictions. This framework provides evolutionary and ecological perspectives on host-microbiome interactions and their implications for host behavior and health, while offering verifiable predictions with potential relevance to clinical treatments.
最近的研究揭示了微生物组影响宿主大脑、行为和健康的机制,并且微生物组失衡——持续的微生物组失衡——与各种慢性疾病的发生和进展有关,包括成瘾行为。然而,对于塑造宿主-微生物组生态系统并影响宿主状态的生态和进化过程的理解仍然有限。在这里,我们提出微生物组内的竞争动态,以及与宿主-微生物组相互调节相关的动态,可能会促进微生物组失衡并加重成瘾行为。我们构建了一个数学框架,对宿主-微生物组生态系统对这些变化的动态进行建模。我们发现,当这个生态系统受到实质性的干扰时,微生物组可能会朝着一种强化新宿主状态的组成方向转变。这种正反馈循环加剧了扰动后的失衡,阻碍了回到初始平衡的尝试,促进了复发发作并延长了成瘾。我们表明,初始微生物组组成是一个关键因素:多样化的微生物组增强了生态系统的弹性,而较低的微生物组多样性更容易导致微生物组失衡,从而加重成瘾。这个框架为宿主-微生物组相互作用及其对宿主行为和健康的影响提供了进化和生态视角,同时提供了具有潜在临床治疗相关性的可验证预测。