Giardiaalters commensal microbial diversity throughout the murine gut

Abstract

Giardia lamblia is 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. 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 use culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the entire 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 bacterial taxa. Specifically, giardiasis 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. 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.

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

“…It was therefore concluded that the microbiota determined the outcome of infection. These studies have recently been complemented with more in-depth investigations of the microbial community, showing changes in the amount of microbiota and its composition upon G. duodenalis infection in mice (Barash et al, 2016). Hence, not only do microbiota influence infection outcome but the parasite in turn alters the gut microbiota.…”

Probiotics enhance susceptibility of mice to cryptosporidiosis

“…Cryptosporidiosis is an enteric infection caused mostly by two species of Cryptosporidium parasites, C. parvum and C. hominis. Transmission occurs when infectious oocysts are ingested, 35 either with contaminated food and water (1,2), by fecal-oral contact and possibly by inhalation (3). Recent surveys have revealed the high prevalence of cryptosporidiosis among infants living in developing nations, where it causes substantial morbidity and mortality in infants less than 2 years of age.…”

“…A characteristic of many intestinal pathologies of infectious or other causes is an increase in the proportion of Gammaproteobacteria (32). Although exceptions to this trend have been reported (33), a shift towards facultative anaerobes reflecting increased permeability of the gut epithelium is a hallmark of infectious(26, 27,34,35), inflammatory(36)(37)(38) and other intestinal pathologies (39). The abundance of 305 Gammaproteobacteria in the distal gut of mice heavily infected with C. parvum is significant because it indicates a shift in the luminal oxygen gradient (40) creating conditions favoring multiplication of Gammaproteobacteria.…”