Exploiting metabolic shifts: gut colonization strategies of the microaerophilic pathogen Campylobacter jejuni

Campylobacter jejuni is a microaerophilic, gram-negative bacterium and one of the leading causes of bacterial gastroenteritis worldwide, most commonly transmitted through contaminated poultry products. The organism exhibits striking host-specific behavior, persisting as a harmless commensal in the chicken intestine while causing inflammatory disease and rapid proliferation in the human gut. Despite its clinical importance, the mechanisms underlying nutrient acquisition, metabolic adaptation, and fitness during infection remain incompletely understood. The ferret model of campylobacteriosis closely reproduces the colonic pathology observed in humans and has provided important insights into how C. jejuni modifies and exploits the intestinal environment during infection. Inflammation induced by infection alters gut physiology, increasing luminal oxygen availability and concentrations of metabolites such as L-lactate. Elevated L-lactate serves as a key nutrient source that enhances C. jejuni growth in vivo, illustrating the broader concept of host-pathogen metabolic crosstalk in which immune-mediated inflammation unintentionally creates nutrient-rich conditions favorable for pathogen expansion. Within the altered redox landscape of the inflamed intestine, redox-responsive signaling pathways may further regulate genes involved in lactate utilization and metabolic adaptation. Although many enteric pathogens produce virulence factors that manipulate host physiology to promote colonization, similar mechanisms in C. jejuni remain poorly defined. This review explores the potential contribution of the cytolethal distending toxin in reshaping the host environment to support bacterial growth and persistence. Understanding these metabolic and regulatory adaptations provides new insight into C. jejuni pathogenesis and highlights potential targets for therapeutic intervention.