Helminth Infection, Gut Microbiome Alterations, and Their Impact on Pulmonary Tuberculosis Susceptibility

Helminth infections and pulmonary tuberculosis (TB) frequently coexist in low- and middle-income countries and interact through immune-mediated mechanisms that influence host susceptibility to Mycobacterium tuberculosis (Mtb). Beyond direct immunomodulation, increasing evidence indicates that helminth infections alter gut microbiome composition and microbial metabolite production, thereby shaping systemic and pulmonary immune responses through the gut-lung axis. Given the central role of the gut microbiome in regulating T-cell polarization, macrophage function, and inflammatory balance, microbiome-mediated pathways have emerged as a potential link between helminth infection and impaired host defense against pulmonary TB.

This narrative review examines current evidence on how helminth-induced immunological changes and gut microbiome alterations, within the context of the gut-lung axis, may influence susceptibility to pulmonary TB.

A narrative review approach was used to synthesize findings from experimental, observational, and clinical studies addressing helminth infection, gut microbiome dynamics, immune regulation, and TB.

Helminth infections are associated with Th2-skewed immune responses characterized by increased regulatory T-cell activity and anti-inflammatory cytokine production, which may attenuate Th1-mediated immunity essential for Mtb control. Helminths also modulate gut microbiome composition, with effects ranging from increased microbial diversity to dysbiosis, depending on helminth species and host context. These microbiome alterations may influence systemic immunity through microbial metabolites such as short-chain fatty acids (SCFAs). Importantly, SCFAs exhibit context-dependent effects, potentially supporting immune homeostasis while, under certain conditions, promoting regulatory pathways that may dampen protective antimycobacterial responses.

Current evidence suggests that helminth-associated immune modulation and gut microbiome alterations may influence pulmonary TB susceptibility, although most findings remain associative rather than causal. Further mechanistic and clinical studies are needed to clarify the role of the gut-lung axis in helminth-TB coinfection and to inform integrated disease management strategies in endemic regions.