H2020 PROGRAM | GoC-MM

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Goc-MM – Gut-On-a-Chip Model and Microbiome

 

GUT MICROBIOTA IN PHYSIOLOGY AND PATHOLOGY

The gut is a structure derived by the embryonic endoderm, dividing during the fetal life into foregut, midgut and hindgut. These primitive gut segments specialize further into the components of the gastrointestinal tract, which has the main function of digesting food, absorbing the nutrients and eliminating the substances not useful for the body. However, the gastrointestinal system is more complex considering its endocrinology, its immunological functions – mainly played by the gut-associated lymphoid tissue (GALT)- and the enteric nervous system also called our “second brain”.

Trillions of microorganisms habit the human gut and their genes (microbioma) is over 100 times more than the human genoma [1]. The human microbiota may undergo modifications throughout life and can be different depending on ethnicity and geography [24]. Microbiota participates in the modulation of intestinal motility, blood flow, immunity, digestions and secretions of metabolites, and perception of visceral signals [5]. In fact, human microbiota represents a sort of fingerprint of each individual participating in the organism homeostasis. Therefore, it is speculated that dysbiosis plays an important role in the pathogenesis and the therapeutic effects of prebiotics and probiotics not only gastrointestinal diseases but also in pathologies related to the cardiovascular system, kidney, liver, central nervous system, skin, eyes, autoimmune disease, diabetes and other metabolic disorders [69].

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GUT ON A CHIP: INSIGHT TO THE PROJECT

Gut-On-a-Chip Model and Microbiome study (Goc-MM) aims at developing a new gut-on-a-chip model, easy to industrialize and commercialize, in order to promote the diffusion of more powerful organ on a chip in vitro models in order to study digestive pathologies and for advanced drug testing. The biological proof of concept to validate this organ on a chip focuses on culturing and studying microbiota phyla composition of healthy subjects and patients with dysmetabolism [10,11]. Goc-MM would be a Gut-on-a-Chip experimental model that enables human intestine epithelial cells and microbiota to be cultured in the presence of physiologically relevant flow and controlling gas composition. Peristalsis-like mechanical deformations will be provided in order to promote and keep the proper phenotype of epithelial cell lineages of the small intestine. Gut-on-a-chip can be a relevant tool for personalized medicine aimed at fine-tunes treatments of microbiota-related diseases (Figure 1).

figure 1 gut on a chip

Figure 1: Representation of Gut-On-a-Chip Model and Microbiome study (Goc-MM) and its foreseeable applications. Goc-MM consists of a small intestine Gut-On-a-Chip perfused by a device able to control: temperature, gas and shear stress/flow while producing rhythmic deformation of the epithelial tissues. This Gut-On-a-Chip may: allow investigating chronic pathologies or specific small intestine physiological pathway; being more relevant than standard in vitro models during the drug development; and is also compatible with personalized medicine approach (from the correct diagnosis to the appropriate therapy).

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INFO

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SKILLS

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FIELD OF APPLICATIONS

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3D CELL ANALYSIS

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DRUG TESTING

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CLINICAL DIAGNOSIS

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TARGETS: DESIGNING A MULTIPURPOSE PLATFORM

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The main challenge in the research field related to the gut microbiota and microbioma is due to the lack of a realistic preclinical model. In fact, not all gut microbiota can be cultured in vitro [12] and because of the different diet and species-specific symbiotic bacteria, there is a big gap between the animal model and humans test [13, 14]. The long term goal of Goc-MM is to provide a clinical diagnostic tool based on microfluidic and 3D-cells co-culture, a kind of advanced cells culture known as Organ-on-a-Chip. The chip design is mainly intended to obtain highly reproducible miniaturized Gut-on-a-Chip to be used as an alternative to in vivo models; in vitro drug assessments; and as an in vitro tool for personalized medicine. Nevertheless, its design and versatility are also intended to facilitate the academic and translational research on gut physiology and pathology.

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BRIDGING THE GAP BETWEEN CLINIC RESEARCH AND INNOVATIVE INDUSTRIES

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Personalized medicine and translational research are in need of new tools to better understand in deep the pathophysiology of the gut as well as the role of the microbiota in preventing and protecting the host from specific diseases. The correlation between microbiota and both metabolic and neurological disorders is supported by the scientific literature[1, 15, 16]. Dr. Giulia Malaguarnera has experienced the unmet need for new and diagnostic tool in clinical research, translating the knowledge from preclinical test (Figure 2). In the frame of the European research plan H2020 much emphasis has been lighted on promoting the collaboration between Academia and Industries, the two sides of innovation. Moreover, the interdisciplinarity environment in which biomedical research meets the engineering will be the key aspects for the career development of Giulia. Establish sound consortium and goals are the key aspects to accelerate innovation which is true only when is available for the whole society.

figure 2 gut on a chip

Figure 2: Insights and targetted applications of Goc-MM.

Goc-MM is a microfluidic gut on a chip that mimics the physiological condition of the human intestine in a 3D in vitro model in what concerns the gut structure, function, physiology and pathology. In fact, this intestine chips may resemble enteropathies condition due to dysbiosis and thus it can be used for biochemical and molecular analysis, cellular culture in which test the mechanical parameters and the drug absorption and efficacy.

[/vc_column_text][vc_separator height_2=”0″ height=”25″ show_border=”no_border”][vc_column_text]The project manager: Dr. Giulia Malaguarnera

Dr. Giulia Malaguarnera is a Marie Curie Fellow. She has worked in pre-clinical and clinical research related to aging, neurodegeneration and dysmetabolism.

Giulia will do a full immersion in the young and dynamic CherryBiotech SAS environment to achieve new expertise and get a deep insight on the fundamental requirements of the future of European innovative industries thus acquiring the vision to promote stronger and more efficient research consortium reducing the gap between academic and industries.

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SPREADING THE MESSAGE

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The European Commission is actively promoting innovation throughout a significant amount of economic efforts. Nevertheless, those are often unreported or poorly understood by the general community outreach. Considering the potential impact of Goc-MM in the field with high ethical significance, as the possibility to replace/reduce animal tests, the meaning and the results achieved by the project will be disseminated to the general outreach trough selected articles in magazines as well as promoting a dedicated symposium in a scientific festival.

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CONSORTIUM

[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_team title=”Dr. DARIO FASSINI” subtitle=”INNOVATION MANAGER” image=”8087″]
[/vc_team][/vc_column_inner][vc_column_inner width=”1/4″][vc_team title=”Dr. GIULIA MALAGUARNERA” subtitle=”R&D project manager” image=”16734″]
[/vc_team][/vc_column_inner][vc_column_inner width=”1/4″][vc_team title=”Dr. ANTONI HOMS CORBERA” subtitle=”CTO (Chief Technology Officer)” image=”17103″]
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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 845036

Disclaimer: this content reflects only the author’s view and the EU Agency is not responsible for the information it contains.

[/vc_column_text][/vc_column][vc_column width=”1/1″][vc_separator height_2=”0″ height=”50″ show_border=”no_border”][vc_column_text]References

  1. Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration.J Physiol. 2017 Jan 15;595(2):489-503. doi: 10.1113/JP273106. Epub 2016 Dec 4.
  2. Amir Bein, Woojung Shin, Sasan Jalili-Firoozinezhad, Min Hee Park, Alexandra Sontheimer-Phelps, Alessio Tovaglieri, Angeliki Chalkiadaki, Hyun Jung Kim, Donald E. Ingber. Microfluidic Organ-on-a-Chip Models of Human Intestine. Cell Mol Gastroenterol Hepatol. 2018; 5(4): 659–668. Published online 2018 Apr 24. doi: 10.1016/j.jcmgh.2017.12.010

  3. Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: What does the future hold? World J Gastroenterol. 2019 Feb 7;25(5):552-566. doi: 10.3748/wjg.v25.i5.552.

  4. Rajilić-Stojanović M, Heilig HG, Tims S, Zoetendal EG, de Vos WM. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012

  5. Gaulke, C.A.; Sharpton, T.J. The influence of ethnicity and geography on human gut microbiome composition. Nat. Med. 2018, 24, 1495–1496

  6. Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment Pharmacol Ther. 2012;35:403–413

  7. Tang WHW, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol. 2019 Mar;16(3):137-154. doi: 10.1038/s41569-018-0108-7.

  8. Malaguarnera G, Giordano M, Nunnari G, Bertino G, Malaguarnera M. Gut microbiota in alcoholic liver disease: pathogenetic role and therapeutic perspectives. World J Gastroenterol. 2014 Nov 28;20(44):16639-48. doi: 10.3748/wjg.v20.i44.16639. 

  9. Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A. Sela, Alexander J. Muller, James M. Mullin, Korin Albert, John P. Gilligan, Katherine DiGuilio, Rima Dilbarova, Walker Alexander, George C. Prendergast. The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists. Cancer Res. 2017 Apr 15; 77(8): 1783–1812. Published online 2017 Mar 14. doi: 10.1158/0008-5472.CAN-16-2929
  10. Pranjul Shah, Joëlle V. Fritz, Enrico Glaab, Mahesh S. Desai, Kacy Greenhalgh, Audrey Frachet, Magdalena Niegowska, Matthew Estes, Christian Jäger, Carole Seguin-Devaux, Frederic Zenhausern, Paul Wilmes. A microfluidics-based in vitro model of the gastrointestinal human–microbe interface. Nat Commun. 2016; 7: 11535. Published online 2016 May 11. doi: 10.1038/ncomms11535

  11. H. J. Kim, D. Huh, G. Hamilton and D. E. Ingber. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip, 2012, 12, 2165–2174.

  12. McGaughey KD, Yilmaz-Swenson T, Elsayed NM, Cruz DA, Rodriguez RR, Kritzer MD, Peterchev AV, Gray M, Lewis SR, Roach J, Wetsel WC, Williamson DE.Comparative evaluation of a new magnetic bead-based DNA extraction method from fecal samples for downstream next-generation 16S rRNA gene sequencing. PLoS One. 2018 Aug 23;13(8):e0202858. doi: 10.1371/journal.pone.0202858. eCollection 2018. Erratum in: PLoS One. 2019 Feb 19;14(2):e0212712.
  13. Hugenholtz F, de Vos WM. Mouse models for human intestinal microbiota research: a critical evaluation.Cell Mol Life Sci. 2018 Jan;75(1):149-160. doi: 10.1007/s00018-017-2693-8. Epub 2017 Nov 9.
  14. Turner PV.The role of the gut microbiota on animal model reproducibility. Animal Model Exp Med. 2018 Jul 28;1(2):109-115. doi: 10.1002/ame2.12022. eCollection 2018 Jun.
  15. Noce A, Marrone G, Di Daniele F, Ottaviani E, Wilson Jones G, Bernini R, Romani A, Rovella V. Impact of Gut Microbiota Composition on Onset and Progression of Chronic Non-Communicable Diseases. Nutrients. 2019 May 14;11(5). pii: E1073. doi: 10.3390/nu11051073.
  16. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 2016 Apr 20;8(1):42. doi: 10.1186/s13073-016-0303-2.

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