Gut microbes modulate Helicoverpa armigera immunity and affect its susceptibility to microbial pathogens.

Emerging research underscores the critical roles of host-associated microbiota in modulating immunity and disease resistance in insects. However, the interplay between gut microbes and innate immune pathways remains incompletely understood in lepidopteran pests. This study investigates if manipulation of the gut microbiome affects immune responses and pathogen susceptibility in Helicoverpa armigera larvae. To do this, the gut microbiome of the larvae was removed using antibiotic treatment. Subsequently, the expression of antimicrobial peptides (AMPs) including attacin and defensin, and antioxidant genes including superoxide dismutase (SOD), dual oxidase (DUOX) and NADPH oxidase (NOX)were assessed following challenge with Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb). Our results revealed that microbiome depletion reduced the expression of attacin and defensin in fat body and gut, and suppressed SOD gene expression in the gut. The bioassay tests showed that depletion of microbiota resulted in increased larval vulnerability to the pathogens compared to the control larvae. We also tested whether microbial infection affects gut microbiota and found that intrahemocoelic microbial injection induced both humoral and gut immunity, resulting in suppression of gut microbiota, highlighting a crosslink between humoral and gut immunity. Together, these results underscore a conserved requirement for microbiota-derived signals in priming specific innate immune pathways and provide insight into how microbiome manipulation may impact the success of biological control strategies. These findings suggest that targeted manipulation of the gut microbiome could be harnessed to enhance pest susceptibility to biocontrol agents, thereby offering a promising avenue for improving microbial pest control.