Disease and symptoms

Hereditary fructose intolerance (HFI) is an uncommon and possibly life-threatening inherited condition. If left undiagnosed, continued ingestion of fructose and other fructose-containing sugars (like sucrose) lead to hepatic and renal failure and growth retardation (Ali et al, 1998), manifesting itself in symptoms like nausea, vomiting, diffuse abdominal pain and hypoglycemia even after the uptake of smallest amounts of sugars (Yasawy et al, 2009). The patient will eventually begin to avoid all kinds of sweet food including most of fruit and vegetables. A particular problem is posed by the nowadays common usage of sucrose and fructose in all kinds of industrial food, therefore it becomes hard to avoid the consumption of small amounts of fructose.

Molecular mechanism

HFI is caused by the catalytic deficiency of Aldolase B, a specialized enzyme of the fructose metabolism catalyzing the cleavage of fructose-1-phosphate into dihydroxyacetone phosphate and glycerine aldehyde. If malfunctioning, fructose-1-phosphate accumulates in liver and renal cells and inhibits various enzymes of glycolysis, gluconeogenesis and glycogen metabolism, leading to hypoglycemia and other symptoms mentioned above.

The project

Our project is based on the idea to give HFI patients their quality of life back by giving them the opportunity to eat fructose-containing food again. We genetically modified the probiotic Lactobacillus johnsonii to metabolize fructose and sucrose instead of glucose by knocking out enzymes involved in glucose metabolism and increasing the uptake and metabolism of sucrose and fructose. The aim was to create a probiotic therapeutic, which effectively removes these metabolites concurrent with digestion and thereby alleviates the symptoms of HFI patients. Therefore, our Lactobacillus johnsonii is an approach to help people suffering from HFI by giving them our probiotic to multiply their former limited options of healthy and delicious food.