The WHO estimates that more than 300 million people worldwide suffer from depression. It is also the world's leading cause of disability (WHO, 2020). Patients nowadays get drugs like antidepressants prescribed to combat these feelings, whereas only one-third of all patients get the desired release of depression and anxiety. Research has shown that the intestinal microbiome alterations play a crucial role in a person's stress reactivity and influences anxiety-like and depression-like behaviors. They called it the (microbiome-)gut-brain axis. The relative abundance of Bacteroidetes species (f.i. Prevotella ) is increased, and the relative abundance of Firmicutes (f.i. Faecalibacterium and Ruminococcus ) is decreased in patients with depression (Liang et al., 2018).
Therefore, we could offer relief to other patients by modulating their intestinal microbiome. This is where the product of our iGEM projects comes into the picture! We present you with an edible pearl with three main components:
Naringenin: A flavonoid with, amongst others, anti-cancer, anti-oxidative and anti-obesity activity (Bugianesi et al. 2002);
Kojibiose: A prebiotic sugar with low caloric value and sweet taste (Beerens et al., 2017);
Vitamin B12: a vitamin for which many people are deficient (Sukumar & Saravanan, 2019).
Acid-resistant layer: protects the active components from getting destructed by gastric enzymes and low pH.
In brief, if we can alter the gut microbiome's functionality, the bidirectional communication might shift and lead to less anxiety and depression-like behaviors.
Our primary goal is to produce naringenin recombinantly in Cupriavidus necator as it seems to be a more ideal host compared to Escherichia coli. Secondly, in order to develop an ideal bubble, we wished to quantitatively investigate the naringenin's diffusion process in a simulation of the human small intestine. We planned to perform dissolution tests to analyze the naringenin release. Due to the COVID-19 pandemic, we were not able to do such experiments because we barely had access to the lab. Nevertheless, we replaced these dissolution experiments by setting up three types of diffusion models. These models approximate the dissolution experiments, whereas they do not consider specific factors as intestinal motility and pH.
We also thought about the business side of our bubble. It could be sold as an independent food supplement, or it also could be added to prebiotic foods like kombucha, yogurt, and kimchi. First of all, this will make it easier for the user to consume the product, and it creates a kind of superfood, whereas its probiotic properties are combined with a prebiotic and vitamins. At the end of the ride we came up with a rough idea for a business model which we can work out and test critically after iGEM. We are truly inspired to study this project further, possibly in partnership with the Ghent University.
Beerens K, De Winter K, Van de Walle D, Grootaert C, Kamiloglu S, Miclotte L L, Van de Wiele T, Van Camp J, Dewettinck K, Koen & Desmet T. (2017) Biocatalytic Synthesis of the Rare Sugar Kojibiose: Process Scale-Up and Application Testing J. Arg and Food Chem. 65(29): 6030-6041. Available at https://pubs.acs.org/doi/abs/10.1021/acs.jafc.7b02258.
Bugianesi R, Catasta G, Spigno P, D’Uva A & Maiani G (2002) Naringenin from cooked tomato paste is bioavailable in men. J. Nutr. 132: 3349–3352 Available at: https://pubmed.ncbi.nlm.nih.gov/12421849/ [Accessed October 10, 2020]
Liang S, Wu X, Hu X, Wang T & Jin F (2018) Recognizing depression from the microbiota–gut–brain axis. Int. J. Mol. Sci. 19: Available at: /pmc/articles/PMC6032096/?report=abstract [Accessed October 5, 2020]
Sukumar N, Saravanan P. (2019). Investigating vitamin B12 deficiency. BMJ 365:I1865. doi: 10.1136/bmj.l1865
WHO (2020) Depression. Available at: https://www.who.int/news-room/fact-sheets/detail/depression [Accessed October 11, 2020]