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Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis.

ABSTRACT: 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.

SUBMITTER: Lewin-Epstein O

PROVIDER: S-EPMC10372008 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis.

Lewin-Epstein Ohad O Jaques Yanabah Y Feldman Marcus W MW Kaufer Daniela D Hadany Lilach L

Communications biology 20230726 1

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 hos ...[more]

PMID: 37495841

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Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.

Dataset Information

Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis.

Publications

Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis.

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