HS_China

Background

Lactose intolerance is a prevalent issue in our world that cannot be overlooked. As much as 75% of the world’s human population is intolerant to ingested dietary lactose. These individuals not only suffer from bloating and diarrhea when drinking milk, but also bear a much higher risk of bone diseases. Unfortunately, alternatives and supplements such as lactose-free milk and lactase drops are expensive and inaccessible to many. Available probiotics and prebiotic also have weak survivability.

Based on these findings, we came up with a syn-bio approach to solve lactose intolerance. We developed a strain of E. coli that can be safely transplanted to the intestines and secret lactase from within, breaking down any lactose that remains troublesome for the digestive system. Not only will this eliminate physical displeasure, but it also will unleash the nutritional value of milk for people who are once unable to digest it.

Our project

Firstly, we decided to use Escherichia coli strain Nissle 1917 as our chassis. E. coli has been the most popular chassis strand with high productivity and maneuverability. Its Nissle 1917 strain, originally discovered in the feces of German Soldiers during the First World War, is a widely used chassis for gastro-intestinal treatment. We aim to use this strand of E. coli to produce β-galactosidase LacZ in the small intestines, an enzyme that can effectively breakdown lactose into glucose and galactose, both degradable by the human digestive track. The produced enzymes will be transported to the extracellular environment through a signal peptide. This makes sure that the bacteria themselves won’t ingest the lactose to produce gasses, effectively stopping all forms of bloating, discomfort or diarrhea.

Second, we plan to use enteric coated pills to contain the freeze-dried bacteria for ingestion. When swallowed, enteric coated pills do not dissolve in the stomach like normal pills would, but only starts to break down in the small intestine. This helps the bacteria bypass the chemical barrier the gastric acid imposes and ensures a safe transport to the intestines.

Third, we aim to create a protective film using CAP, capsular polysaccharides surrounding Escherichia coli strain Nissle 1917, to ensure that the bacteria safely implants itself in the intestinal environment without damage. The gene for the CAP will be encoded in the bacteria so it will be spontaneously produced. The CAP helps the bacteria adapt to a wider range of temperature and pH, shuts out harmful chemicals and toxins, as well as assisting them to stick to the intestinal wall.