Effects of giardiasis on iron, hepcidin, and gut microbiota metabolites in young rats: Evidence for systemic inflammation and malabsorptive metabolic reprogramming.

BACKGROUND: Giardiasis is one of the most common intestinal parasites affecting young mammals, birds, and humans. Giardiasis is also frequently associated with the malabsorption of nutrients, particularly iron. However, the effects of Giardia lamblia on iron metabolism and overall inflammation in the host have not been fully understood.

AIM: This study aimed to investigate giardiasis in experimentally infected young rats and its impact on the systemic response of the host following the parasite clearance from the intestine. More specifically, this study focuses on the body's iron regulation, the response of the protein hepcidin, and the body's metabolites.

METHODS: A total of 36 weaned, young male Wistar rats were assigned to one of the following three groups: uninfected control, infected with G. lamblia in the acute phase (day 7), and post-infected phase (day 21). All rats in the infected groups received 1 × 106 G. lamblia trophozoites by oral gavage. Biochemical parameters of interest in the blood and serum of all rats were determined. These were iron, total iron binding capacity, transferrin saturation (TSAT), ferritin, hepcidin, erythropoietin (EPO), C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-α, albumin, and prealbumin. The metabolites of interest were kynurenine, citrulline, trimethylamine oxide (TMAO), lactate, succinate, and short-chain fatty acids (SCFAs). The metabolites were determined by high-performance liquid chromatography and gas chromatography-mass spectrometry.

RESULTS: The infected groups had significantly lower serum iron, TSAT, albumin, and citrulline (p < 0.01). Levels of ferritin and hepcidin decreased significantly post-infection (p < 0.001) and were associated with increased IL-6 and CRP levels. The metabolites kynurenine and TMAO were significantly increased, whereas the SCFAs (especially butyrate and acetate) were significantly lower. These results suggest an imbalance in the gut microbiota and metabolic reprogramming. A drop in EPO levels was also observed, which, together with the lower levels of Mean corpuscular volume and Mean Corpuscular Hemoglobin, indicates that the host was in the early stages of anemia.

CONCLUSION: Infection with G. lamblia in younger rats causes systemic inflammation, and the iron in the body is sequestered. Significant disruption of the host's microflora and the metabolites derived from the host and the microbes is also observed. These findings support the role of post-infectious metabolic dysregulation in giardiasis and the risk of damage restricted to the intestinal tract alone.