Team:Thessaly/Description
Project Description
Overview
Malnutrition is a global phenomenon that affects a major part of humanity. According to a World Health Organization (WHO) report (WHO, 2016), today, nearly one in three people globally suffer from at least one form of malnutrition: wasting, stunting, vitamin and mineral deficiency, overweight or obesity and diet-related non-communicable diseases. Inability to absorb nutrients can lead to chronic diseases, such as Inflammatory Bowel Diseases (IBDs), causing a variety of symptoms, such as diarrhea, anemia, fever, high heart rate and many more, that further aggravate the problem. IBDs are a multifactorial family of interrelated diseases that affect the human gut, which affects that 1 in 1000 people worldwide in 2020 (Crohn's & Colitis Foundation,2020). To tackle this complicated issue, we develop a personalized platform for diagnosis and treatment of IBDs, using modular Synthetic Biology tools.
Inspiration from the World
Creating a team was a difficult task…
Finding our cause was a challenge...
What was that cause, which concerned all of us in one way or another? What was the problem that our society, friends, family were facing?
As we had friends and family who suffer because of chronic inflammation of the digestive tract, IBDs, we understood that this was the era of our mission.
Malnutrition is a modern and global health challenge, causing and/or inducing many chronic diseases. After contacting specialists the need to fight this problem became clear to us. Read more
Inspiration from iGEM projects
iGEM is about creating innovative ideas by building upon existing knowledge, so we wanted to utilize the efforts of previous iGEM teams to build our project. During the journey of our research, studying iGEM projects was one of our main concerns, as we wanted to get inspired by the work of previous iGEMers. Our research led us to projects that tackle IBD or malnutrition, but most of them, without a common link to connect them. We got inspired by TU_Eindhoven 2015 for the diagnosis, since they wanted to use aptamers as recognition elements to sense virtually Calprotectin, as a biomarker that is associated with Crohn’s disease and Colitis. However, they didn’t get to test their idea for that specific target. Considering this, we decided to use their biosensor that can be implemented in the intestines and use Calprotectin as a biomarker for diagnosis of inflammation, using a different form of sample that isn’t commonly used; saliva. We, also, got inspired by Team NEU_CHINA 2018/2019 and Team SHSBNU China that created the biosensor for the intestinal tract of patients with IBD using as a biomarker, Nitric oxide, which is a natural signaling molecule of inflammation. We used their approach to tackle this issue considering a way to evaluate the microbiome, as a way of understanding and relieving the problem in this area. Moreover, the work of Team UFlorida 2018 was an inspiring project, because they introduce us to the healing properties of butyrate, which we chose as one of the Short-Chain Fatty Acids, SCFAs, that we use as our four therapeutic modules. Finally Team Duesseldorf, created a biosensor sensing free fatty acids, giving us the idea of using pFliC, a butyrate- induced, as a part of our system. Taking everything into consideration we combined our ideas with our newfound inspiration and we developed our project; Amalthea. For more information about our project design Click here
Facts
Malnutrition is one of the common problems that afflict the poor in low- and middle-income countries, presenting as a major concern in the era of Sustainable Development Goals (SDGs) in which achieving the goals is imperative (Adebisi et al., 2019). According to a World Health Organization (WHO) report (WHO, 2016), today, nearly one in three people globally suffer from at least one form of malnutrition: wasting, stunting, vitamin and mineral deficiency, overweight or obesity and diet-related non-communicable diseases. Moreover, WHO refers to deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients.
An aspect of malnutrition-induced immunological deficiency is the comorbidity with Inflammatory Bowel Diseases (IBDs), being prevalent in up to 70% of patients with active disease and up to 38% of patients in remission. IBDs have been associated with increased hospitalizations and poor clinical outcome (Balestrieri et al., 2020), as well as being connected to changes in gut microbiota (Lim et al., 2018). In IBD patients, malnutritional deficits are mostly manifested with vitamin A, B, D & K, zinc, and iron deficiencies (Jayawardena et al., 2020). IBDs consist a heterogeneous and multifactorial class of chronic, relapsing inflammatory disorders that affect the Gastrointestinal (GI) tract, with Crohn's Disease (CD) and Ulcerative Colitis (UC) being the principal representatives of this family of syndromes (Balestrieri et al., 2020).
Recent years
In recent years, the science community has turned its focus on the gut microbiota in search of a different approach to the diagnosis of IBDs, leading to SCFAs. SCFAs have been utilized as metabolites possessing both diagnostic and therapeutic value. The gut microbiota ferments indigestible carbohydrates (e.g. dietary fibers) and produces mainly SCFAs, such as acetate, propionate, and butyrate (Müller et al., 2019). Among them, the fermentation of undigested dietary components is of paramount importance for the physiology and metabolism of the host. The subsequent microbial released metabolites have a key role in the interplay between bacterial producers and other gut inhabitants as well as with the host cells (Rios-Covian et al., 2020).
What is our goal?
Amalthea: A modular platform for monitoring gastrointestinal health
We aim to fight malnutrition and IBDs from a different angle, trying to improve the gut environment and essentially provide a chance for people to eat whatever their hearts desires.
Amalthea is a complete, personalized, modular platform, which monitors the function of gut microbiota for non-invasive diagnosis and tailored treatment of IBDs. This year, we build the monitoring system, a capsule hosting a bio-electronic interface. Bacteria engineered to detect the molecular footprint of gut microbiota are combined with an electronic module to digitalize and transmit the data.
Amalthea is designed to support a balanced way of living with less dietary restrictions and improved well-being.
How ?
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Cell-free salivary Calprotectin detection
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Bio-electronic ingestible detection capsule
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Alleviation of Symptoms
Consequently, fecal Calprotectin has proven to be useful in the diagnostic work-up of patients with suspected IBDs, but can also be used as a surrogate marker for the presence of endoscopic inflammation, as well as an early prognostic marker for upcoming disease activity in patients in remission, thus holding the potential to monitor the disease over time. A different approach to this matter is the use of the potential of salivary Calprotectin to reflect disease activity and treatment response using serum concentrations as a positive control. Investigating effects on salivary Calprotectin was found that Calprotectin in the saliva is elevated in IBD patients and is related to IBD activity and treatment (Majster M, et. al., 2019)
The non-invasive encapsulated detection device consists of two modules, a genetically engineered bacteria-based module, and an electronic module. Succeeding in the communication between our inner world and the one outside of it, through the understanding of our body’s needs. This will be possible by identifying metabolite deficiencies directly correlated to IBD, exploiting a bio-electronic interface to enable real- time monitoring on the patient’s smartphone. Concluding, the micro-bio-electronic ingestible device will support physicians in better assisting and accommodating to what their patients require, primarily those who suffer from IBDs, contributing to the improvement of their well-being and quality of life.
The therapeutic module has the form of a bacteria-based system capable of producing SCFAs. SCFAs can be used in multiple ways, including therapeutics, considering their anti-inflammatory properties and their effect on the gut microbiota. The microbiome plays a substantial role in controlling the normal function of the intestine and contributes to the deflection of inflammation and systemic disease (Ho SM, et. al., 2019). A crucial aspect of our project is to create personalized treatments for the patients by replenishing the missing amount of SCFAs, which will be provided by probiotics that will initiate their production (Markowiak-Kopeć et al., 2020).
Safety
Due to various parameters, the interaction among the capsule, the genetically engineered bacteria, and human cells faces many safety, security, and ethical risks. The first barrier that protects us and the environment is the capsule itself that acts as a mechanical barrier. We designed a “kill switch”, as a second barrier, in order to ensure that we can keep the patients safe (Aizenman et al., 1996).
In that context, we have integrated double layer biosafety and biocontainment levels into our final product, not only to ensure that it can be consumed by the patient without any risk or fear, but also to protect the natural dynamics of the ecosystem from artificial forms of life.
The first barrier that protects us and the environment is the capsule itself that acts as a mechanical barrier. The second level of biosafety is based on a standardized methodology, which utilizes “kill switches”. For more information Click here
Some objections to our product are expected, due to the misinformation of the general public, and the aversion towards trying new methods to solve problems in new innovative and unknown ways. The key is to inform people about our project and encounter the patients with honesty and determination to redefine the human body as an ecosystem and the human being as a superorganism, rather than being a single individual. This re- understanding of ourselves will be necessary, in order to create a mindset that the human microbiome is considered as an important factor to the general function of the human body. For more information Click here
References
Adebisi, Y. A., Ibrahim, K., Lucero-Prisno, D. E., Ekpenyong, A., Micheal, A. I., Chinemelum, I. G., & Sina-Odunsi, A. B. (2019). Prevalence and Socio-economic Impacts of Malnutrition Among Children in Uganda. Nutrition and Metabolic Insights, 12, 117863881988739. https://doi.org/10.1177/1178638819887398
Aizenman, E., Engelberg-Kulka, H., & Glaser, G. (1996). An Escherichia coli chromosomal “addiction module” regulated by 3′,5′-bispyrophosphate: A model for programmed bacterial cell death. Proceedings of the National Academy of Sciences of the United States of America, 93(12), 6059–6063. https://doi.org/10.1073/pnas.93.12.6059
Al Mijan, M., & Lim, B. O. (2018). Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends. World Journal of Gastroenterology, 24(25), 2673–2685.https://doi.org/10.3748/wjg.v24.i25.2673
Balestrieri, P., Ribolsi, M., Guarino, M. P. L., Emerenziani, S., Altomare, A., & Cicala, M. (2020). Nutritional aspects in inflammatory bowel diseases. Nutrients, 12(2). https://doi.org/10.3390/nu12020372
Crohn's & Colitis Foundation,(2020), TAKE ACTION FOR WORLD IBD DAY!, https://www.crohnscolitisfoundation.org/WorldIBDDay
Day, R. L. J., Harper, A. J., Woods, R. M., Davies, O. G., & Heaney, L. M. (2019). Probiotics: Current landscape and future horizons. Future Science OA, 5(4). https://doi.org/10.4155/fsoa-2019-0004
Hafezi H, Robertson TL, Moon GD, Au-Yeung KY, Zdeblick MJ, Savage GM. An ingestible sensor for measuring medication adherence. IEEE Trans Biomed Eng. 2015;62(1):99-109. doi:10.1109/TBME.2014.2341272
Ho SM, Lewis JD, Mayer EA, et al. Challenges in IBD Research: Environmental Triggers [published correction appears in Inflamm Bowel Dis. 2019 Nov 14;25(12):e171]. Inflamm Bowel Dis. 2019;25(Suppl 2):S13-S23. doi:10.1093/ibd/izz076
JACOBSON B, MACKAY RS. A pH-endoradiosonde. Lancet. 1957;272(6981):1224. doi:10.1016/s0140-6736(57)91792-0
Jayawardena, D., & Dudeja, P. K. (2020). Micronutrient Deficiency in Inflammatory Bowel Diseases: Cause or Effect? Cmgh, 9(4), 707–708. https://doi.org/10.1016/j.jcmgh.2019.12.009
Kourosh Kalantar-zadeh, Nam Ha, Jian Zhen Ou, and Kyle J. Berean, (2017), Ingestible Sensors, ACS Sensors 2017 2 (4), 468-483 https://doi.org/10.1021/acssensors.7b00045
Lim, H.-S., Kim, S.-K., & Hong, S.-J. (2018). Food Elimination Diet and Nutritional Deficiency in Patients with Inflammatory Bowel Disease. Clinical Nutrition Research, 7(1), 48. https://doi.org/10.7762/cnr.2018.7.1.48
Majster M, Almer S, Boström EA. Salivary calprotectin is elevated in patients with active inflammatory bowel disease, 2019, Arch Oral Biol.,107:104528. https://doi.org/10.1016/j.archoralbio.2019.104528
Manceau H, Chicha-Cattoir V, Puy H, Peoch K. Fecal calprotectin in inflammatory bowel diseases: update and perspectives. Clin Chem Lab Med. 2017;55(4):474-483. https://doi.org/10.1515/cclm-2016-0522
Markowiak-Kopeć P. , Śliżewska K. The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome. Nutrients. 2020;12(4):1107. Published 2020 https://doi.org/10.3390/nu12041107
Parada Venegas D, De la Fuente MK, Landskron G, et al. Short Chain Fatty Acids (SCFAs)- Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases [published correction appears in Front Immunol. 2019 Jun 28;10:1486]. Front Immunol. 2019;10:277. Published 2019 Mar 11. https://doi.org/10.3389/fimmu.2019.00277
Spray C., Debelle G., and Murphy M., (2001) Current diagnosis, management and morbidity in paediatric inflammatory bowel disease, Acta Paediatrica, vol. 90, no. 4, pp. 400–405. Majster M, Almer S, Boström EA. Salivary calprotectin is elevated in patients with active inflammatory bowel disease, 2019, Arch Oral Biol.,107:104528.
Rios-Covian D, González S, Nogacka AM, et al. An Overview on Fecal Branched Short-Chain Fatty Acids Along Human Life and as Related With Body Mass Index: Associated Dietary and Anthropometric Factors. Front Microbiol. 2020;11:973. Published 2020 May 27. https://doi.org/10.3389/fmicb.2020.00973
UNICEF, Malnutriton, New York, March 2020
World Health Organization. (2016). The double burden of malnutrition: policy brief. World Health Organization. https://apps.who.int/iris/handle/10665/255413. License: CC BY-NC-SA 3.0 IGO
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