Translating priority effects and niche engineering into rational microbiome therapeutics across the gut-lung axis

Area of Science:

• Microbiome ecology
• Host-microbe interactions
• Translational medicine

Background:

• The human microbiome maintains homeostasis via colonization resistance, a defense disrupted by antibiotics.
• Antibiotic-induced dysbiosis creates a pathogen-permissive state, a 'dysbiotic trap,' hindering recovery and increasing susceptibility to infections, including respiratory infections via the gut-lung axis.

Purpose of the Study:

• To propose a framework for 'rational microbiome engineering' to overcome the limitations of current empirical therapies.
• To outline strategies for durable microbiome restoration and host immune homeostasis.

Main Methods:

• Systematic review of ecological principles governing microbiome stability and disruption.
• Analysis of mechanisms linking gut dysbiosis to systemic immune impairment (e.g., gut-lung axis).
• Proposal of targeted interventions: precision niche clearing with bacteriophages, harnessing priority effects, and engrafting synthetic microbial consortia (SMCs).

Main Results:

• Dysbiosis, triggered by perturbations like antibiotics, leads to a stable but detrimental 'dysbiotic trap.'
• Gut metabolite depletion (e.g., short-chain fatty acids) impairs immune cell function in distal sites (e.g., alveolar macrophages).
• Current empirical therapies like fecal microbiota transplantation (FMT) often fail due to the difficulty in reversing dysbiosis.

Conclusions:

• Microbiome medicine must shift from empirical approaches to rational engineering for effective treatment.
• Precision niche clearing, strategic timing (priority effects), and rationally designed synthetic microbial consortia (SMCs) are key components.
• This engineered approach promises to durably resolve dysbiosis and restore systemic immune homeostasis.