Intestinal worms beneficially influence the composition of gut microbiota in the presence of inflammatory bowel disease, a new study suggests. The findings provide important insights into how intestinal worms, or helminths, manipulate the gut microbiota in a way that is beneficial for its host. Building upon previous research, Deepshika Ramanan and colleagues found that mice deficient in the gene Nod2, which are used to model Crohn's disease, develop abnormalities in their small intestines, including a compromised layer of mucus and changes to intestinal cell morphology. These alterations allowed for greater colonization by the bacteria Bacteroides vulgatus. The team found that chronic infection of these mice with the helminth Trichuris muris restored the mucus and cell morphology within the small intestines. A closer look at inflammatory markers revealed that the parasitic worms help inhibit B. vulgatus via the immune signaling molecules, interleukin (IL)-4 and IL-13, which was confirmed by knocking out a relevant transcription factor. Similar and even more profound results were found with a second type of helminth. Monitoring the gut microbiota of the mice over the course of infection revealed that the parasites help increase the colonization of strains of a different family of bacteria, Clostridiales, at the expense of B. vulgatus. Inflammatory bowel disease is less prevalent in regions where helminth infection is very common. Therefore, Ramanan et al. studied an indigenous population in Malaysia that has a very high rate of infection of intestinal worms, analyzing stool samples collected from individuals before and after deworming treatment. They detected significant changes in gut microbiota composition, where Clostridiales was the most significantly reduced order, and Bacteroidales was significantly expanded following treatment. These results reveal an intriguing and beneficial facet of a symbiotic relationship between helminths and humans.