The gut micro-environment
Enteric viruses and hypoxia
The intestinal lumen is characterized by low oxygen levels (hypoxia). This hypoxic gut environment is known to be critical for maintaining a healthy microbiota. However, the impact of this gut-specific hypoxic environment on the interaction between intestinal epithelial cells and enteric viruses remains poorly understood.
To investigate how hypoxia affects the host-enteric virus interface, we use rotavirus as a model enteric pathogen. Our research has revealed that hypoxia renders cells more permissive to viral infection by modulating antiviral immunity in the gut. We are now addressing the underlying mechanisms and investigating whether manipulation of the signaling pathways leading to hypoxia-mediated immune dampening in the gut could be exploited to treat patients with chronic enteric virus infections.
The importance of hypoxia in regulating intestinal epithelium stemness.
The intestinal epithelium maintains homeostasis through a balance of stem cell proliferation and differentiation. Within the crypt-villus structures, an oxygen gradient is created with low-oxygen levels at the villus tips (hypoxia) and normoxic levels of oxygens at the crypt-containing stem cells. Using patient-derived organoids, we explore the molecular mechanisms connecting oxygen availability to stem cell function and epithelial homeostasis.
Cryptosporidium parvum and hypoxia
The enteric protozoan parasites Cryptosporidium parvum (C. parvum) causes acute gastroenteritis leading to abdominal pain and watery diarrhea. In immunocompromised individuals, infections can become prolonged and potentially fatal. Our research focuses on how the gut’s low-oxygen environment influences C. parvum infection. To investigate this, we culture intestinal epithelial cells under normoxic and hypoxic conditions and study infections with the enteric pathogen C. parvum.
