Giardiaalters commensal microbial diversity throughout the murine gut

Abstract

ABSTRACTGiardia lambliais the most frequently identified protozoan cause of intestinal infection. Over one billion people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in endemic areas. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear as the parasite neither produces a known toxin nor induces a robust inflammatory response.Giardiacolonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact ofGiardiainfection on the host microbiota, we use culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the entire gastrointestinal tract in mice infected withGiardia. We discovered thatGiardia’scolonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic bacterial taxa. Specifically, giardiasis is typified by both expansions in aerobicProteobacteriaand decreases in anaerobicFirmicutesandMelainabacteriain the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murineGiardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Thus giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite’s unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variation in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.