Team:BOKU-Vienna
All bellies are beautiful, but not all of them are happy.
One in seven bellies suffers from a bowel disorder.
With Friendzyme we are taking oral enzyme therapy to the next level. We want to help people with irritable bowel syndrome (IBS), non-celiac gluten sensitivity (NCGS) and related disorders by implementing a novel therapeutic platform where bacteria are enclosed in a biocompatible, mucoadhesive capsule to deliver fructan-degrading enzymes medium-term and right where they are needed.
What are FODMAPs?
FODMAPs, short for fermentable oligo-, di-, monosaccharides, and polyols, are a diverse group of complex carbohydrates that cannot be broken down by human digestive enzymes.
They act as nutritional fiber and are metabolized to gas by our natural microbiome. However, in patients with irritable bowel syndrome (IBS) and non-celiac gluten sensitivity (NCGS), this process causes abdominal pain, diarrhea, bloating, headache and nausea and can also lead to psychological symptoms, like depression.
FODMAPs are found in high concentrations in a huge variety of foods like:
- Cereals (wheat, rye, …)
- Vegetables (onions, garlic, artichoke, …)
- Fruit (peaches, melon, apples, …)
- Dairy products (products with lactose, like milk and cheese)
- Processed foods (artifical sweeteners, added fiber, …)
Impact
Today, 15% of the general population suffer from bowel disorders like irritable bowel syndrome (IBS) and non-celiac gluten sensitivity (NCGS). These disorders are still poorly understood, and diagnosis as well as treatment options are limited.
Recent studies have shown that the symptoms of up to 70% of IBS patients could be relieved by the exclusion of FODMAPs from their diet. However, this diet is highly restrictive as FODMAPs are found in almost all groups of food, and patients often have long and complex lists of “forbidden” foods, which are hard to navigate.
As most restaurants do not accomodate the requirements of a low-FODMAPs diet, many patients face restrictions in their social life. In addition to the emotional stress, low-FODMAPs diets can lead to nutritional deficits if not planned correctly.
We want to change that by creating
Your buddy for your belly!
We are the iGEM 2021 team from Vienna, consisting of 25 students from diverse scientific disciplines, and we are creating Friendzyme to address neglected gastrointestinal diseases by tackling one of the most common FODMAPs groups: fructans. Fructans are fructose polymers that occur all over different groups of food and are, therefore, particularly hard to avoid.
How can this buddy actually help a belly?
Our project uses a three-fold approach:
- Genetically modified lactobacilli express and release enzymes for the degradation of fructans to fructose and its subsequent conversion to glucose.
- The bacteria are enclosed in a biocompatible scaffold that protects the bacteria from extreme pH values and digestive enzymes.
- The surface of the scaffold is designed to adhere to the mucosa of the gut and keep the capsule in the gut for 24 hours.
The three-step approach enables the site-directed delivery of fructan-degrading enzymes over a prolonged timespan instead of the short-term administration, as in current enzyme therapies.
In the lab, we used Golden Gate Cloning to engineer L.plantarum to express the enzymes endo-inulinase, levanase and invertase. We synthesized mucoadhesive scaffolds from cellulose sulfate and polyDADMAC for encapsulation and tested the toxicity of these capsules in vitro Caco-2 cells. Furthermore, we modeled the degradation of the two main fructans, inulin and levan, to fructose and, subsequently, to glucose.
Future Prospects
Our mission is to make the life of people suffering from IBS and related disorders easier. With one pill per day, our approach would allow patients to eat fructan-containing foods, while staying freem from symptoms.
We sincerely hope that out concept of site-directed, medium-term oral enzyme therapy will be taken up by other research projects and that such bacterial biofactories will one day help people with all kinds of problems, be it a food sensitivity, a different disorder or even hormone-free contraception!
