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Problem Overview

Diet influences both energy balance and microbiota directly. The microbial composition is affected by determining which nutrients become available to the microbes residing in the gut and thus which microbes thrive or regress (Fluitman, 2017). According to the Food and Agricultural Organisation (FAO) , unhealthy diets are at the root of the global obesity and diet-related non-communicable disease (NCD) pandemic (FAO, 2019).

Unhealthy diets account for a large share of the burden of non-communicable diseases in Europe, accounting for an estimated 86% of deaths and 77% of the disease burden in the region which represents 70- 80% of European healthcare costs (WHO, 2020).

Currently, one in three people worldwide is malnourished while 1,9 billion and 462 million are overweight and underweight, respectively. (Fluitman, 2017). Malnutrition affects health, well-being, and ability to work. Elderly people with chronic disease, poorer population groups and socially isolated individuals are at a particular risk (European Commision, 2020) In order to properly prevent or treat malnutrition, a thorough understanding of all contributing factors is needed.

If a disrupted microbial composition is indeed instrumental in the development of malnutrition, microbial manipulation would pose an appealing topic of further investigation, contributing in the development of a wide range of innovative of therapeutic and preventive strategies (Fluitman, 2017).

Gut Microbiome: Establishing The Missing
Link Between NCDs And Nutrition

The gastrointestinal (GI) tract harbors trillions of microorganisms (CCFA, 2014). The gut microbiome plays a critical role in the integrity of the intestinal barrier, nutrient absorption, metabolic homeostasis, and immune maturity, particularly in the early stages of life (Robertson, 2020).

Dietary components can alter the intestinal microenvironment favoring some bacteria over others. That can affect the microbe–microbe interactions involved in the fermentation of indigestible nutrients, and thus the modulation of energy extraction (Xiao, 2019) (Fluitman, 2017).

Dysbioses are correspondingly not simply structural changes in the gut microbiota, but are instead associated with major impairments in many fundamental microbial metabolic functions with potential impact on the host (Morgan, 2012). During disease, GI microbiomes are characterized by shifts in bacterial populations that are highly functionally coordinated (FAO, 2019).

Our Solution

AMALTHEA aims to develop a complete prevention toolkit able to Detect, Evaluate, and Ameliorate Gut Dysbiosis.

We developed a bio-capsule to quantify the existence of Short Chain Fatty Acids (SCFAs) in the gut flora. The data is digitized and transmitted to a mobile application, where a multidisciplinary team of health experts can evaluate the data received. If dysbiosis is detected, we aim to alleviate it by the usage of a living biotherapeutic, synbiotic nutritional supplement.

Detect

Gut flora is an emerging therapeutic target for functional bowel disorders, a variety of metabolic diseases and neuropsychiatric disorders. A growing body of research implicates Short Chain Fatty Acids (SCFAs) , derived from gut flora, as the mechanistic basis to positively affect various pathological processes. These SCFAs are produced through bacterial fermentation of otherwise indigestible polysaccharides, oligosaccharides, and proteins (Xiao, 2019) (Fluitman, 2017).

One commonly reported alteration associated with GI disorders is a decrease in short-chain fatty acid (SCFA)–producing bacteria, and particularly butyrate-synthesizing species such as Roseburia and Faecalibacterium prausnitzii (Ferrer-Picón, 2019).

That’s why we developed AMALTHEA, a bio-electronic ingestible capsule that detects the absence of SCFAs. Our non-invasive encapsulated detection device consists of two modules, a genetically engineered bacteria-based module, and an electronic module. Through AMALTHEA, we are enabling real-time monitoring and site-specific measurement of the SCFAs production in the colon.

Evaluate

After the detection device completes its scan of the gut flora, it is important to receive this valuable data for further analysis and evaluate the condition of the user. But how?

Throughout those two years, the COVID-19 pandemic has highlighted even more the need for access to e-health services. The use of digital applications is becoming increasingly present in our daily lives as a way of organizing and managing the effective delivery of health services (European Commission, 2016). In order to live up to the global modernization and increase data accessibility and security , we’ve developed e-AMALTHEA, a digital application that receives the data from the microcapsule through Bluetooth, after transforming the signal from biological to electrochemical. We’re exploiting a bio-electronic interface to enable real- time monitoring on the patient’s smartphone. With e-AMALTHEA, users can monitor their health, adapt their lifestyle, and interact with a multidisciplinary team of health professionals that provide feedback on their condition. Through integrated and personalized care, gathers the benefits of e-health services in one application, to benefit both the patients and the health system. (European Commission, 2017) (European Commission, 2018).

Ameliorate

If shortage of SCFAs is detected and gut dysbiosis is on the rise, our team proposes a two-way solution to stop dysbiosis on its tracks: Nutrition assessment and personalization, accompanied with a living bio-therapeutic synbiotic supplement.

Hippocrates’ notion “Let food be thy medicine and medicine be thy food” is as timely as ever, since many studies nowadays confirm this claim: dietary intervention is essential micro-ecological homeostasis and then impact host physiology and health (Xiao, 2019). Mediterranean diet adherence particularly influences microbial plant polysaccharide degradation potential, SCFAs production and pectin metabolism. An acute, dietary switch can affect microbial composition within 24 h. However, this switch must be sustained for the microbial composition to remain stable. The microbiota likely adapt to a specific diet, optimizing fermentation and thus SCFA production. An integrated manner is key for improving human health via dietary modification because the gut microbiome explicitly engages in a bidirectional relationship with diet (Fluitman, 2017) (Wang, 2021).

However, since the world is looking for the best path towards nourishing 10 billion people (FAO, 2019) , food resources become vital and personalized nutrition is not enough. Microbiota-manipulating interventions aim to promote specific beneficial bacterial species or repress others. The ultimate goal of these interventions is to permanently alter the microbial composition, even after the intervention’s end.

With the advancements in synthetic biology, the probiotic engineering offers more flexibility and fine-tuning capacity than others (Aggarwal, 2021). That’s why we propose to ameliorate gut dysbiosis with CERAS, a living bio-therapeutic synbiotic supplement, that can act as a living, SCFA producing factory for the gut flora. We engineered a probiotic strain and encapsulated it in prebiotic fibers that produces SCFAs at a pinpoint location in the user’s gut. We alleviate gut dysbiosis in a personalized manner, ensuring continuing stability on the gut’s microbiome health.


For more technical details visit our Engineering page.

Through COVID-19 we understood what it means to be alone. While the majority of research funding was handed on COVID research, we observed a new wave of support for digital health applications and telemedicine to combat other major disorders safely, away from COVID spikes zones. Being in Greece, this newly found digital transformation has elevated the need to connect our capital of Athens with rural areas, mainland Greece with Greek islands and decentralise health care, making it available for everyone. Through Amalthea, we aim to bridge the gap between scatered health services and provide a tool for those suffering alone and in silence. We bring cutting-new technologies like microbiome manipulation and disease prevention back home!

References

  1. Aggarwal, N., Breedon, A. M. E., Davis, C. M., Hwang, I. Y., & Chang, M. W. (2020). Engineering probiotics for therapeutic applications: recent examples and translational outlook. Current Opinion in Biotechnology, 65, 171–179. doi:10.1016/j.copbio.2020.02.016

  2. Crohn’s & Colitis Foundation of America (CCFA, 2014), The Facts about Inflammatory Bowel DiseasesEuropean Commission, (2016), “eHealth: connecting health systems in Europe”.

  3. European Commission, (2017) “STATE OF HEALTH IN THE EU 2017”, Companion Report

  4. European Commission, (2018) “Digital Health and Care TRANSFORMATION OF HEALTH AND CARE IN THE DIGITAL SINGLE MARKET”

  5. European Commission (2020) FOOD 2030 Pathways for Action: HEALTHY, SUSTAINABLE AND PERSONALISED NUTRITION.

  6. FAO (2019) MICROBIOME: THE MISSING LINK? SCIENCE AND INNOVATION FOR HEALTH, CLIMATE AND SUSTAINABLE FOOD SYSTEMS

  7. Ferrer-Picón, E., Dotti, I., Corraliza, A. M., Mayorgas, A., Esteller, M., Perales, J. C., … Salas, A. (2019). Intestinal Inflammation Modulates the Epithelial Response to Butyrate in Patients With Inflammatory Bowel Disease. Inflammatory Bowel Diseases. doi:10.1093/ibd/izz119

  8. Kristina S. Fluitman, Nicolien C. De Clercq, Bart J.F. Keijser, Marjolein Visser, Max Nieuwdorp & Richard G. IJzerman (2017): The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids, Expert Review of Endocrinology & Metabolism, DOI: 10.1080/17446651.2017.1318060

  9. Morgan et al.: Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biology 2012 13:R79.

  10. Robertson R. (2020), The Gut Microbiome in Child Malnutrition

  11. Wang, D. D., Nguyen, L. H., Li, Y., Yan, Y., Ma, W., Rinott, E., … Huttenhower, C. (2021). The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nature Medicine, 27(2), 333–343. doi:10.1038/s41591-020-01223-3

  12. Xiao, S., Jiang, S., Qian, D., & Duan, J. (2019). Modulation of microbially derived short-chain fatty acids on intestinal homeostasis, metabolism, and neuropsychiatric disorder. Applied Microbiology and Biotechnology,104(2), 589–601. doi:10.1007/s00253-019-10312-4

igem.thessaly@gmail.com