Cross-kingdom dialogs in the gut: Integrating bacterial pathogens, helminths, and microbiota interactions for immune homeostasis

The interactions between bacterial pathogens, helminths, and commensal microbiota in the gut form a complex ecological network that profoundly impacts host immunity and health. Pathogens employ strategies such as type VI secretion systems (T6SS) and inflammation induction to evade colonization resistance, disrupt microbial balance, and establish self-benefit ecological niches. These interactions involve competition with commensal bacteria and helminths, which play a critical role in maintaining gut homeostasis by occupying ecological niches, competing for nutrient, and supporting the mucus barrier. Meanwhile, helminths can modulate commensal bacterial gene expression, metabolic activity, and survival by secreting excretory–secretory products. In addition, by inducing a Th2 immune response, helminths can enhance the intestinal mucosal barrier, alter the gut microbiota composition, and thereby inhibit bacterial pathogen colonization. Interestingly, helminths and pathogens can exhibit synergistic or competitive relationships. For instance, Ascaris lumbricoides may provide a survival niche for Vibrio cholerae, while helminths can also indirectly inhibit pathogenic bacteria through immune modulation. These intricate interactions influence gut microbial composition, digestion, and immune function, and are closely associated with diseases. Future research should focus on elucidating the molecular mechanisms underlying these interactions. Understanding the interactions between pathogens, helminths, and commensal microbiota not only provides novel insights into maintaining host immune homeostasis but also establishes a theoretical foundation for future development of gut health intervention strategies.