Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface

Marc Mac Giolla Eain, Joanna Baginska, Kacy Greenhalgh, Joëlle V. Fritz, Frederic Zenhausern, Paul Wilmes

Engineering ›› 2017, Vol. 3 ›› Issue (1) : 60-65.

PDF(1780 KB)
PDF(1780 KB)
Engineering ›› 2017, Vol. 3 ›› Issue (1) : 60-65. DOI: 10.1016/J.ENG.2017.01.011
Research
Research

Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface

Author information +
History +

Abstract

Host-microbe interactions at the gastrointestinal interface have emerged as a key component in the governance of human health and disease. Advances in micro-physiological systems are providing researchers with unprecedented access and insights into this complex relationship. These systems combine the benefits of microengineering, microfluidics, and cell culture in a bid to recreate the environmental conditions prevalent in the human gut. Here we present the human-microbial cross talk (HuMiX) platform, one such system that leverages this multidisciplinary approach to provide a representative in vitro model of the human gastrointestinal interface. HuMiX presents a novel and robust means to study the molecular interactions at the host-microbe interface. We summarize our proof-of-concept results obtained using the platform and highlight its potential to greatly enhance our understanding of host-microbe interactions with a potential to greatly impact the pharmaceutical, food, nutrition, and healthcare industries in the future. A number of key questions and challenges facing these technologies are also discussed.

Keywords

Microbiome / Microfluidics / Organ-on-a-chip / HuMiX

Cite this article

Download citation ▾
Marc Mac Giolla Eain, Joanna Baginska, Kacy Greenhalgh, Joëlle V. Fritz, Frederic Zenhausern, Paul Wilmes. Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface. Engineering, 2017, 3(1): 60‒65 https://doi.org/10.1016/J.ENG.2017.01.011

References

[1]
Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016;14(8):e1002533.
CrossRef Pubmed Google scholar
[2]
Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol 2015;31(1):69–75.
CrossRef Pubmed Google scholar
[3]
Pflughoeft KJ, Versalovic J. Human microbiome in health and disease. Annu Rev Pathol 2012;7(1):99–122.
CrossRef Pubmed Google scholar
[4]
Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007;104(34):13780–5.
CrossRef Pubmed Google scholar
[5]
Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012;13(10):701–12.
CrossRef Pubmed Google scholar
[6]
Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et alMicrobial dysbiosis in colorectal cancer (CRC) patients. PLoS One 2011;6(1):e16393.
CrossRef Pubmed Google scholar
[7]
Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 2015;26:26191.
CrossRef Pubmed Google scholar
[8]
Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013;34(1):39–58.
CrossRef Pubmed Google scholar
[9]
Naseer MI, Bibi F, Alqahtani MH, Chaudhary AG, Azhar EI, Kamal MA, et alRole of gut microbiota in obesity, type 2 diabetes and Alzheimer’s disease. CNS Neurol Disord Drug Targets 2014;13(2):305–11.
CrossRef Pubmed Google scholar
[10]
Azcárate-Peril MA, Sikes M, Bruno-Bárcena JM. The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol 2011;301(3):G401–24.
CrossRef Pubmed Google scholar
[11]
Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, et alGut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 2015;30(3):350–8.
CrossRef Pubmed Google scholar
[12]
Panzer AR, Lynch SV. Influence and effect of the human microbiome in allergy and asthma. Curr Opin Rheumatol 2015;27(4):373–80.
CrossRef Pubmed Google scholar
[13]
Roume H, Muller EE, Cordes T, Renaut J, Hiller K, Wilmes P. A biomolecular isolation framework for eco-systems biology. ISME J 2013;7(1):110–21.
CrossRef Pubmed Google scholar
[14]
Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et alMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009;106(10):3698–703.
CrossRef Pubmed Google scholar
[15]
Heintz-Buschart A, May P, Laczny CC, Lebrun LA, Bellora C, Krishna A, et alIntegrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes. Nat Microbiol 2016;2:16180.
CrossRef Google scholar
[16]
Fritz JV, Desai MS, Shah P, Schneider JG, Wilmes P. From meta-omics to causality: experimental models for human microbiome research. Microbiome 2013;1(1):14.
CrossRef Pubmed Google scholar
[17]
Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M, Heikenwalder M, et alReversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 2010;328(5986):1705–9.
CrossRef Pubmed Google scholar
[18]
Parlesak A, Haller D, Brinz S, Baeuerlein A, Bode C. Modulation of cytokine release by differentiated CACO-2 cells in a compartmentalized coculture model with mononuclear leucocytes and nonpathogenic bacteria. Scand J Immunol 2004;60(5):477–85.
CrossRef Pubmed Google scholar
[19]
Nguyen TLA, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research? Dis Model Mech 2015;8(1):1–16.
CrossRef Pubmed Google scholar
[20]
Arnold JW, Roach J, Azcarate-Peril MA. Emerging technologies for gut microbiome research. Trends Microbiol 2016;24(11):887–901.
CrossRef Pubmed Google scholar
[21]
Sung JH, Yu J, Luo D, Shuler ML, March JC. Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip 2011;11(3):389–92.
CrossRef Pubmed Google scholar
[22]
Kim HJ, Huh D, Hamilton G, Ingber DE. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 2012;12(12):2165–74.
CrossRef Pubmed Google scholar
[23]
Kim HJ, Li H, Collins JJ, Ingber DE. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci USA 2016;113(1):E7–15.
CrossRef Pubmed Google scholar
[24]
Marzorati M, Vanhoecke B, De Ryck T, Sadaghian Sadabad M, Pinheiro I, Possemiers S, et alThe HMI™ module: a new tool to study the host-microbiota interaction in the human gastrointestinal tract in vitro. BMC Microbiol 2014;14:133.
CrossRef Pubmed Google scholar
[25]
Shah P, Fritz JV, Glaab E, Desai MS, Greenhalgh K, Frachet A, et alA microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat Commun 2016;7:11535.
CrossRef Pubmed Google scholar
[26]
Roume H, Muller EE, Cordes T, Renaut J, Hiller K, Wilmes P. A biomolecular isolation framework for eco-systems biology. ISEM J 2013;7(1):110–21.
CrossRef Google scholar
[27]
Sheridan WG, Lowndes RH, Young HL. Intraoperative tissue oximetry in the human gastrointestinal tract. Am J Surg 1990;159(3):314–9.
CrossRef Pubmed Google scholar
[28]
Schmidt TM, Kao JY. A little O2 may go a long way in structuring the GI microbiome. Gastroenterology 2014;147(5):956–9.
CrossRef Pubmed Google scholar
[29]
Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9(5):313–23.
CrossRef Pubmed Google scholar
[30]
Lee PJ, Hung PJ, Lee LP. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 2007;97(5):1340–6.
CrossRef Pubmed Google scholar
[31]
Jang KJ, Suh KY. A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 2010;10:36–42.
CrossRef Google scholar
[32]
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010;328(5986):1662–8.
CrossRef Pubmed Google scholar

Acknowledgements

The authors acknowledge the support from all staff members at the Luxembourg Center for Systems Biomedicine (LCSB) at the University of Luxembourg and at the Center for Applied Nanobioscience and Medicine (ANBM) at the University of Arizona, in particular the contributions of Audrey Frachet (LCSB) and Linda Wampach (LCSB) for illustrations and Matthew Barrett (ANBM). The work of Marc Mac Giolla Eain and Joanna Baginska is supported by a proof-of-concept grant (PoC/15/11014639) to Paul Wilmes and Joëlle V. Fritz through the CORE programme (CORE/14/BM/8066232). The proof-of-concept work on HuMiX was supported by an ATTRACT programme grant (ATTRACT/A09/03), a CORE programme grant (CORE/11/BM/1186762), a European Union Joint Programming in Neurodegenerative Diseases grant (INTER/JPND/12/01), a proof-of-concept grant (PoC15/11014639), an Accompany Measures mobility grant (12/AM2c/05), and an Aide à la Formation Recherché (AFR) postdoctoral grant (AFR/PDR 2013-1/BM/5821107), all funded by the Luxembourg National Research Fund (FNR).

Compliance with ethics guidelines

Authors Frederic Zenhausern and Paul Wilmes have corresponding patent applications, which are currently pending PCT Pub. Nos. WO2013EP055712, WO2013EP065718, and WO201344253; US Provisional App. No. 62/166940; and PCT App. NO. PTC/EP2016/062024.
Marc Mac Giolla Eain, Joanna Baginska, Kacy Greenhalgh, Joëlle V. Fritz, Frederic Zenhausern, and Paul Wilmes declare that they have no conflict of interest or financial conflicts to disclose.
Funding
 

RIGHTS & PERMISSIONS

2017 2017 THE AUTHORS. Published by Elsevier LTD on behalf of the Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
AI Summary AI Mindmap
PDF(1780 KB)

Accesses

Citations

Detail

Sections
Recommended

/