Western Diet Increases the Severity of Giardia Infection in Association with Gut Microbiota Dysbiosis
Authors: Allain Thibault , de Lamache Dimitri Desmonts , Sosnowski Olivia , Fekete Elena , Motta Jean-Paul , Feener Troy D. , Reimer Raylene , Buret Andre G. 
Published: April 2020

AIMSGiardia duodenalis is a protozoan parasite responsible for giardiasis, a leading cause of diarrheal disease worldwide. Giardia sp. infection disrupts the host’s intestinal barrier, leading to acute, chronic, and post‐infectious gut disorders. Giardia infections are prevalent in countries with poor sanitation as well in developed countries, although disease manifestations may vary. Western diet (WD), characterized by a high intake of fat, is known to promote the development of gut inflammatory conditions. In this context, we investigated the impact of short‐term consumption of a WD on the severity and duration of giardiasis. We hypothesized that WD may contribute to the persistence of Giardia in the gut, in association with increased disease severity and microbiota dysbiosis.METHODSC57/BL6 mice were fed for two weeks with 5TJN Western high fat diet (WD) or 5TJS low‐fat (LF) diet prior to infection with Giardia duodenalis GS/M (human isolate). Gut motility and stool water content were assessed before sacrifice at day 7 post infection (PI). Small intestine and colonic sections were collected at day 7 PI for parasite burden and histopathological study. Hypoxia in the colon was assessed by injecting pimonidazole prior to euthanasia. Gut microbiota composition was determined by Illumina Mi‐Seq 16S RNA sequencing. The effect of oleic and palmitic acids (characteristic of HF diets) on Giardia trophozoite metabolic activity was determined by resazurin assay (0.1–0.25 mM). Tight junction disruption in the small intestinal cell line SCNB (dog) infected with G. duodenalis Assemblage A (NF strain) and Assemblage B (GS/M strain) in presence of oleic or palmitic acid (0.3 mM) or both was determined by immunofluorescence.RESULTSGiardia infected C57/BL6 mice fed with WD exhibited a higher trophozoite burden 7 days PI compared to LF infected mice (p<0.001). Giardia infected mice also exhibited enhanced mucosal damage (villus‐crypt ratio) when fed with WD compared to LF infected mice (p<0.01). Increased gut motility (p<0.01) and increased water stool content (p<0.05) were observed in WD infected mice. Giardia infected WD mice exhibited microbiota dysbiosis, with fecal microbiota analysis indicating an increase of Verrucomicrobia and decrease of Firmicutes. Giardia infection caused colonic mucosal normoxia only in mice given a WD. Giardia trophozoite metabolic activity was enhanced in the presence of oleic acid and palmitic acid. Oleic and palmitic acids worsened the disruption of tight junctional proteins (ZO‐1, Claudin‐1 and 4) in non‐transformed intestinal epithelial SCBN cell monolayers infected with G. duodenalis (NF and GS/M isolates).CONCLUSIONThis study gives new insight into how diet may influence the outcome of parasitic diseases. The findings suggest that short term consumption of WD may increase the severity of giardiasis by, at least in part, promoting the growth of Giardia through fatty acid supplementation, predisposing to loss of epithelial integrity, and facilitating microbiota modulation. Therefore, diet intervention such as low‐dietary fat may be beneficial during parasitic enteritis.Support or Funding InformationNSERC