Giardia Alters Commensal Microbial Diversity throughout the Murine Gut

Abstract

Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. 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. Giardia colonization 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 of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia. We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. 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 variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.KEYWORDS Giardia, microbiome, parasite, pathogenesis G iardia lamblia is a microaerophilic protozoan parasite of humans and animals that causes significant morbidity and diarrheal disease worldwide (1, 2). Giardiasis is a zoonotic disease with diverse animal reservoirs. Parasites infect and complete their life cycle in mammalian hosts, and infected animals shed Giardia cysts into water supplies. Over 200 million people are estimated to have acute or chronic giardiasis, and rates of giardiasis approach 90% in areas where it is endemic (3, 4). When prevalent, giardiasis has been implicated as a primary cause of growth restriction for children, resulting in long-term consequences, such as stunting, failure to thrive, malnutrition, and cognitive disabilities (1, 2, 5). In addition, Giardia has been associated with substantial postclearance irritable bowel symptoms in both children and adults (1, 6-8). The significant and adverse impact of giardiasis on global human health contrasts with a considerable lack of resea...

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis

“…Since microbiota were shown to influence the outcome of infection, our lab and the Dawson group conducted the first culture-independent assessment of the intestinal microbiota during Giardia infections and found that infections influence both the architecture and abundance of the intestinal microbiota in the small intestine [37]. While this report emphasizes data using Giardia -infected mice that were pre-treated with antibiotics, and although antibiotic treatment itself causes a shift in the microbiota composition, the overall shift in microbial ecology was still present in infected mice that had not been treated with antibiotics.…”

“…While this report emphasizes data using Giardia -infected mice that were pre-treated with antibiotics, and although antibiotic treatment itself causes a shift in the microbiota composition, the overall shift in microbial ecology was still present in infected mice that had not been treated with antibiotics. A decrease in the diversity and abundance of the obligate anaerobic Firimicutes taxa occurred, while an increase in the diversity of the taxa of aerobic Rhodocyclaceae, Moraxellaceae , Flavobacteriales , and Comomonadaceae was reported [37]. These enriched taxa are all considered to be metabolically flexible, and prosper with increased oxygen tension, lipid availability, and competition for arginine.…”

“…However, this result must be further examined as the data was provided from 12 year-frozen samples and were taken from a study that was not designed to examine the intestinal microbiota composition [38]. The two latest studies identifying the taxa of duodenal microbiota during murine Giardia infections both use samples extracted from intestinal segments for sequencing rather than fecal samples [30, 37]. However, bacterial community analysis derived from fecal samples of non-antibiotic treated, infected mice were indistinguishable when compared to uninfected control mice [30].…”

“…Furthermore, this effect also appears to be Giardia strain dependent [25]. As Giardia can alter intestinal microbial communities [37] it would be interesting to understand the link between intestinal microbial diversity, Giardia , and immune cells leading to subsequent immunopathology.…”

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

“…Although some cross-domain research aims to gain closer insight into apparently pathogenic protists (e.g. Giardia) and their relationships with bacterial microbiota in producing host disease (Barash et al 2017), many studies explore more positive interactions. In many such cross-domain analyses, distribution patterns are used to formulate hypotheses about the evolved nature of these interactions, such as the lower abundances of fungi being seen as a "reservoir" for certain functional interactions in particular contexts (Huffnagle and Noverr 2013).…”