| Summary: | The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in <i>Helicobacter pylori</i> (<i>Hp</i>)-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to <i>Hp</i> and participate in conservative co-evolution with an intricate microbiome. β-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during <i>Hp</i> infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to β-defensins in <i>Hp</i>-associated infections. In microbial infections, mostly in precancerous lesions induced by <i>Hp</i> infection, these modifications could lead to different outcomes.
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