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Intestinal parasitic nematodes live in intimate contact with the host microbiota which poses the question of an interaction of intestinal nematodes with the microbial environment. We used Ascaris suum infection of pigs and Heligmosomoides polygyrus infection in mice to study the triangle relationship between the intestinal nematodes, the host immune response and the gut microbiota. We asked whether the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. Our data show that H. polygyrus-infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3+RORgt+ regulatory T cells and decreased parasite fecundity. In addition, we asked whether the small intestinal parasites produce factors with antimicrobial activity. We detected native, unconcentrated nematode excretory/secretory (ES) products from larvae and adult worms to display broad-spectrum antibacterial activities. In addition, adult A. suum ES products interfered with biofilm formation of Escherichia coli, and caused bacterial agglutination. Mass spectrometry analyses displayed several proteins with known and predicted antimicrobial activities, indicating A. suum to use a variety of factors with broad-spectrum antibacterial activity to affirm itself within a microbe-rich environment. Thus, intestinal nematodes release antimicrobials and benefit from microbiota-driven host immune regulation.