Abstract
Simulated human gastrointestinal (GI) tract systems are important for their applications in the fields of probiotics, nutrition and health. To date, various in vitro gut systems have been available to study GI tract dynamics and its association with health. In contrast to in vivo investigations, which are constrained by ethical considerations, in vitro models have several benefits despite the challenges involved in mimicking the GI environment. These in vitro models can be used for a range of research, from simple to dynamic, with one compartment to several compartments. In this review, we present a panoramic development of in vitro GI models for the first time through an evolutionary timeline. We tried to provide insight on designing an in vitro gut model, especially for novices. Latest developments and scope for improvement based on the limitations of the existing models were highlighted. In conclusion, designing an in vitro GI model suitable for a particular application is a multifaceted task. The bio-mimicking of the GI tract specific to geometrical, anatomical and mechanical features remains a challenge for the development of effective in vitro GI models. Advances in computer technology, artificial intelligence and nanotechnology are going to be revolutionary for further development. Besides this, in silico high-throughput technologies and miniaturisation are key players in the success of making in vitro modelling cost-effective and reducing the burden of in vivo studies.
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The data collected to write this review will be made available by the authors without undue reservation to any qualified researchers.
References
Sensoy I (2021) A review on the food digestion in the digestive tract and the used in vitro models. Curr Res Food Sci 4:308–319. https://doi.org/10.1016/j.crfs.2021.04.004
Fournier E, Roussel C, Dominicis A, Ley D, Peyron M, Collado V et al (2022) In vitro models of gut digestion across childhood: current developments, challenges and future trends. Biotechnol Adv 54:107796. https://doi.org/10.1016/j.biotechadv.2021.107796
Lucas-González R, Viuda-Martos M, Pérez-Alvarez JA, Fernández-López J (2018) In vitro digestion models suitable for foods: opportunities for new fields of application and challenges. Food Res Int 107:423–436. https://doi.org/10.1016/j.foodres.2018.02.055
Nissen L, Casciano F, Gianotti A (2020) Intestinal fermentation in vitro models to study food-induced gut microbiota shift: an updated review. FEMS Microbiol Lett 367:fnaa097. https://doi.org/10.1093/femsle/fnaa097
Ahire JJ, Kashikar MS, Madempudi RS (2020) Survival and germination of Bacillus clausii UBBC07 spores in in vitro human gastrointestinal tract simulation model and evaluation of clausin production. Front Microbiol 11:1010. https://doi.org/10.3389/fmicb.2020.01010
Ahire JJ, Neelamraju J, Madempudi RS (2020) Behavior of Bacillus coagulans Unique IS2 spores during passage through the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model. LWT-Food Sci Technol 124:109196. https://doi.org/10.1016/j.lwt.2020.109196
Ahire JJ, Mokashe NU, Kashikar MS, Madempudi RS (2022) Survival of Limosilactobacillus reuteri UBLRu-87 during passage through the in vitro gut model system. LWT-Food Sci Technol 164:113652. https://doi.org/10.1016/j.lwt.2022.113652
Pham VT, Mohajeri MH (2018) The application of in vitro human intestinal models on the screening and development of pre-and probiotics. Benef Microbes 9:725–742. https://doi.org/10.3920/BM2017.0164
Kostewicz ES, Abrahamsson B, Brewster M, Brouwers J, Butler J, Carlert S et al (2014) In vitro models for the prediction of in vivo performance of oral dosage forms. Eur J Pharm Sci 57:342–366. https://doi.org/10.1016/j.ejps.2013.08.024
Li C, Yu W, Wu P, Chen XD (2020) Current in vitro digestion systems for understanding food digestion in human upper gastrointestinal tract. Trends Food Sci Technol 96:114–126. https://doi.org/10.1016/j.tifs.2019.12.015
Minekus M, Alminger M, Alvito P, Ballance S, Bohn T, Bourlieu C et al (2014) A standardised static in vitro digestion method suitable for food – an international consensus. Food Funct 5:1113–1124. https://doi.org/10.1039/C3FO60702J
Minekus M, Marteau P, Havenaar R, Veld J (1995) A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern Lab Anim 23:197–209. https://doi.org/10.1177/026119299502300205
Clark RL, Connors BM, Stevenson DM, Hromada SE, Hamilton JJ, Amador-Noguez D et al (2021) Design of synthetic human gut microbiome assembly and butyrate production. Nat Commun 12:1–16. https://doi.org/10.1038/s41467-021-22938-y
Morrison AB, Campbell JA (1960) The relationship between physiological availability of salicylates and riboflavin and in vitro disintegration time of enteric coated tablets. J Am Pharm Assoc 49:473–478. https://doi.org/10.1002/jps.3030490717
Cressman WA, Janicki CA, Johnson PC, Doluisio JT, Braun GA (1969) In vitro dissolution rates of aminorex dosage forms and their correlation with in vivo availability. J Pharm Sci 58:1516–1520. https://doi.org/10.1002/jps.2600581220
Davis RE, Hartman CW, Fincher JH (1971) Dialysis of ephedrine and pentobarbital from whole human saliva and simulated saliva. J Pharm Sci 60:429–432. https://doi.org/10.1002/jps.2600600318
Braybrooks MP, Barry BW, Abbs ET (1975) The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations. J Pharm Pharmacol 27:508–515. https://doi.org/10.1111/j.2042-7158.1975.tb09493.x
Miller TL, Wolin MJ (1981) Fermentation by the human large intestine microbial community in an in vitro semicontinuous culture system. Appl Environ Microbiol 42:400–407. https://doi.org/10.1128/aem.42.3.400-407.1981
Macfarlane GT, Cummings JH, Macfarlane S, Gibson GR (1989) Influence of retention time on degradation of pancreatic enzymes by human colonic bacteria grown in a 3-stage continuous culture system. J Appl Bacteriol 67:521–527. https://doi.org/10.1111/j.1365-2672.1989.tb02524.x
Molly K, Vande Woestyne M, Verstraete W (1993) Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl Microbiol Biotechnol 39:254–258. https://doi.org/10.1007/BF00228615
Van den Abbeele P, Roos S, Eeckhaut V, MacKenzie DA, Derde M, Verstraete W et al (2012) Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli. Microb Biotechnol 5:106–115. https://doi.org/10.1111/j.1751-7915.2011.00308.x
Possemiers S, Pinheiro I, Verhelst A, Van den Abbeele P, Maignien L, Laukens D et al (2013) A dried yeast fermentate selectively modulates both the luminal and mucosal gut microbiota and protects against inflammation, as studied in an integrated in vitro approach. J Agri Food Chem 61:9380–9392. https://doi.org/10.1021/jf402137r
Marzorati M, Vanhoecke B, De Ryck T, Sadaghian Sadabad M, Pinheiro I, Possemiers S et al (2014) The HMI™ module: a new tool to study the host-microbiota interaction in the human gastrointestinal tract in vitro. BMC Microbiol 14:1–14. https://doi.org/10.1186/1471-2180-14-133
Minekus M, Smeets-Peeters M, Bernalier A, Marol-Bonnin S, Havenaar R, Marteau P et al (1999) A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl Microbiol Biotechnol 53:108–114. https://doi.org/10.1007/s002530051622
Cordonnier C, Thévenot J, Etienne-Mesmin L, Denis S, Alric M, Livrelli V et al (2015) Dynamic in vitro models of the human gastrointestinal tract as relevant tools to assess the survival of probiotic strains and their interactions with gut microbiota. Microorganisms 3:725–745. https://doi.org/10.3390/microorganisms3040725
Wickham M, Faulks R (2007) WO/2007/010238 WIPO. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2007010238. Accessed 14 Nov 2022
Kong F, Singh RP (2010) A human gastric simulator (HGS) to study food digestion in human stomach. J Food Sci 75:E627–E635. https://doi.org/10.1111/j.1750-3841.2010.01856.x
Guerra A, Denis S, le Goff O, Sicardi V, François O, Yao AF et al (2016) Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine. Biotechnol Bioeng 113:1325–1335. https://doi.org/10.1002/bit.25890
Chen L, Xu Y, Fan T, Liao Z, Wu P, Wu X et al (2016) Gastric emptying and morphology of a ‘near real’ in vitro human stomach model (RD-IV-HSM). J Food Eng 183:1–8. https://doi.org/10.1016/j.jfoodeng.2016.02.025
Barroso E, Cueva C, Peláez C, Martínez-Cuesta MC, Requena T (2015) Development of human colonic microbiota in the computer-controlled dynamic SIMulator of the GastroIntestinal tract SIMGI. LWT-Food Sci Technol 61:283–289. https://doi.org/10.1016/j.lwt.2014.12.014
Wright ND, Kong F, Williams BS, Fortner L (2016) A human duodenum model (HDM) to study transport and digestion of intestinal contents. J Food Eng 171:129–136. https://doi.org/10.1016/j.jfoodeng.2015.10.013
Wang P, Rubio A, Duncan H, Donachie E, Holtrop G, Lo G et al (2020) Pivotal roles for pH, lactate, and lactate-utilizing bacteria in the stability of a human colonic microbial ecosystem. mSystems 5:e00645–20. https://doi.org/10.1128/mSystems.00645-20
Berner A, Fuentes S, Dostal A, Payne AN, Vazquez Gutierrez P, Chassard C et al (2013) Novel Polyfermentor Intestinal Model (PolyFermS) for controlled ecological studies: validation and effect of pH. PloS One 8:e77772. https://doi.org/10.1371/journal.pone.0077772
Fehlbaum S, Chassard C, Haug MC, Fourmestraux C, Derrien M, Lacroix C (2015) Design and investigation of PolyFermS in vitro continuous fermentation models inoculated with immobilized fecal microbiota mimicking the elderly colon. PLoS One 10:e0142793. https://doi.org/10.1371/journal.pone.0142793
Cieplak T, Wiese M, Nielsen S, Van de Wiele T, van den Berg F, Nielsen DS (2018) The smallest intestine (TSI)—a low volume in vitro model of the small intestine with increased throughput. FEMS Microbiol Lett 365:fny231. https://doi.org/10.1093/femsle/fny231
Wiese M, Khakimov B, Nielsen S, Sørensen H, van den Berg F, Nielsen DS (2018) CoMiniGut—a small volume in vitro colon model for the screening of gut microbial fermentation processes. PeerJ 6:e4268. https://doi.org/10.7717/peerj.4268
Ekins S, Rose J (2002) In silico ADME/Tox: the state of the art. J Mol Graph Model 20:305–309. https://doi.org/10.1016/S1093-3263(01)00127-9
Yamashita F, Hashida M (2004) In silico approaches for predicting ADME properties of drugs. Drug Metab Pharmacokinet 19:327–338. https://doi.org/10.2133/dmpk.19.327
Kamerman DJ, Wilkinson MH (2002) In silico modelling of the human intestinal microflora. International Conference on Computational Science. Springer, Berlin, Heidelberg, pp 117–126
Jong P, Vissers MM, van der Meer R, Bovee-Oudenhoven IM (2007) In silico model as a tool for interpretation of intestinal infection studies. Appl Environ Microbiol 73:508–515. https://doi.org/10.1128/2FAEM.01299-06
Jamei M, Marciniak S, Feng K, Barnett A, Tucker G, Rostami-Hodjegan A (2009) The Simcyp® population-based ADME simulator. Expert Opin Drug Metab Toxicol 5:211–223. https://doi.org/10.1517/17425250802691074
Sjögren E, Westergren J, Grant I, Hanisch G, Lindfors L, Lennernäs H et al (2013) In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: application of the mechanistic absorption model GI-Sim. Eur J Pharm Sci 49:679–698. https://doi.org/10.1016/j.ejps.2013.05.019
Barth BB, Henriquez CS, Grill WM, Shen X (2017) Electrical stimulation of gut motility guided by an in silico model. J Neural Eng 14:066010. https://doi.org/10.1088/1741-2552/aa86c8
Lin C, Culver J, Weston B, Underhill E, Gorky J, Dhurjati P (2018) GutLogo: agent-based modeling framework to investigate spatial and temporal dynamics in the gut microbiome. PLoS One 13:e0207072. https://doi.org/10.1371/journal.pone.0207072
Tanner SA, Chassard C, Zihler Berner A, Lacroix C (2014) Synergistic effects of Bifidobacterium thermophilum RBL67 and selected prebiotics on inhibition of Salmonella colonization in the swine proximal colon PolyFermS model. Gut Pathog 6:1–12. https://doi.org/10.1186/s13099-014-0044-y
Vamanu E (2017) Effect of gastric and small intestinal digestion on lactic acid bacteria activity in a GIS1 simulator. Saudi J Biol Sci 24:1453–1457. https://doi.org/10.1016/j.sjbs.2015.06.028
Ceuppens S, Uyttendaele M, Drieskens K, Heyndrickx M, Rajkovic A, Boon N et al (2012) Survival and germination of Bacillus cereus spores without outgrowth or enterotoxin production during in vitro simulation of gastrointestinal transit. Appl Environ Microbiol 78:7698–7705. https://doi.org/10.1128/AEM.02142-12
Molly K, Woestyne MV, Smet ID, Verstraete W (1994) Validation of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) reactor using microorganism-associated activities. Microb Ecol Health Dis 7:191–200. https://doi.org/10.3109/08910609409141354
Martoni C, Bhathena J, Jones ML, Urbanska AM, Chen H, Prakash S (2007) Investigation of microencapsulated BSH active Lactobacillus in the simulated human GI tract. J Biomed Biotechnol 2007:13684. https://doi.org/10.1155/2007/13684
Oomen AG, Rompelberg CJM, Bruil MA, Dobbe CJG, Pereboom DPKH, Sips AJAM (2003) Development of an in vitro digestion model for estimating the bioaccessibility of soil contaminants. Arch Environ Contam Toxicol 44:0281–0287. https://doi.org/10.1007/s00244-002-1278-0
Brodkorb A, Egger L, Alminger M, Alvito P, Assunção R, Ballance S et al (2019) INFOGEST static in vitro simulation of gastrointestinal food digestion. Nat Protoc 14:991–1014. https://doi.org/10.1038/s41596-018-0119-1
Van den Abeele J, Rubbens J, Brouwers J, Augustijns P (2017) The dynamic gastric environment and its impact on drug and formulation behaviour. Eur J Pharm Sci 96:207–231. https://doi.org/10.1016/j.ejps.2016.08.060
Humphrey SP, Williamson RT (2001) A review of saliva: normal composition, flow, and function. J Prosthet Dent 85:162–169. https://doi.org/10.1067/mpr.2001.113778
Hedren E, Diaz V, Svanberg U (2002) Estimation of carotenoid accessibility from carrots determined by an in vitro digestion method. Eur J Clin Nutr 56:425–430. https://doi.org/10.1038/sj.ejcn.1601329
Passannanti F, Nigro F, Gallo M, Tornatore F, Frasso A, Saccone G et al (2017) In vitro dynamic model simulating the digestive tract of 6-month-old infants. PLoS One 12:e0189807. https://doi.org/10.1371/journal.pone.0189807
Cueva C, Gil-Sánchez I, Tamargo A, Miralles B, Crespo J, Bartolomé B et al (2019) Gastrointestinal digestion of food-use silver nanoparticles in the dynamic SIMulator of the GastroIntestinal tract (simgi®). Impact on human gut microbiota. Food Chem Toxicol 132:110657. https://doi.org/10.1016/j.fct.2019.110657
Farré R, Tack J (2013) Food and symptom generation in functional gastrointestinal disorders: physiological aspects. Am J Gastroenterol 108:698–706. https://doi.org/10.1038/ajg.2013.24
Nugent SG, Kumar D, Rampton DS, Evans DF (2001) Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 48:571–577. https://doi.org/10.1136/gut.48.4.571
Fallingborg J (1999) Intraluminal pH of the human gastrointestinal tract. Dan Med Bull 46:183–196
Maurer AH (2016) Gastrointestinal motility, part 2: small-bowel and colon transit. J Nucl Med Technol 44:12–18. https://doi.org/10.2967/jnumed.113.134551
Schneyer LH, Young JA, Schneyer CA (1972) Salivary secretion of electrolytes. Physiol Rev 52:720–777. https://doi.org/10.1152/physrev.1972.52.3.720
Varga G (2015) Physiology of the salivary glands. Surgery 33:581–586. https://doi.org/10.1016/j.mpsur.2015.09.003
Bornhorst GM, Singh RP (2014) Gastric digestion in vivo and in vitro: how the structural aspects of food influence the digestion process. Annu Rev Food Sci Technol 5:111–132. https://doi.org/10.1146/annurev-food-030713-092346
Campbell J, Berry J, Liang Y (2019) Anatomy and physiology of the small intestine. In: Yeo CJ (ed) Shackelford’s surgery of the alimentary tract. Elsevier, pp 817–841
Klindt-Toldam S, Larsen SK, Saaby L, Olsen LR, Svenstrup G, Müllertz A et al (2016) Survival of Lactobacillus acidophilus NCFM® and Bifidobacterium lactis HN019 encapsulated in chocolate during in vitro simulated passage of the upper gastrointestinal tract. LWT-Food Sci Technol 74:404–410. https://doi.org/10.1016/j.lwt.2016.07.053
Denaro M, Smeriglio A, Trombetta D (2021) Antioxidant and anti-inflammatory activity of Citrus flavanones mix and its stability after in vitro simulated digestion. Antioxidants 10:140. https://doi.org/10.3390/antiox10020140
Byrd JC, Bresalier RS (2000) Alterations in gastric mucin synthesis by Helicobacter pylori. World J Gastroenterol 6:475. https://doi.org/10.3748/2Fwjg.v6.i4.475
McConnell EL, Fadda HM, Basit AW (2008) Gut instincts: explorations in intestinal physiology and drug delivery. Int J Pharm 364:213–226. https://doi.org/10.1016/j.ijpharm.2008.05.012
Curto AL, Pitino I, Mandalari G, Dainty JR, Faulks RM, Wickham MSJ (2011) Survival of probiotic lactobacilli in the upper gastrointestinal tract using an in vitro gastric model of digestion. Food Microbiol 28:1359–1366. https://doi.org/10.1016/j.fm.2011.06.007
Rémond D, Shahar DR, Gille D, Pinto P, Kachal J, Peyron MA et al (2015) Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition. Oncotarget 6:13858. https://doi.org/10.18632/oncotarget.4030
Braghetto I, Davanzo C, Korn O, Csendes A, Valladares H, Herrera E et al (2009) Scintigraphic evaluation of gastric emptying in obese patients submitted to sleeve gastrectomy compared to normal subjects. Obes Surg 19:1515–1521. https://doi.org/10.1007/s11695-009-9954-z
Szarka LA, Camilleri M (2012) Methods for the assessment of small-bowel and colonic transit. Semin Nucl Med 42:113–123. https://doi.org/10.1053/j.semnuclmed.2011.10.004
Dekaboruah E, Suryavanshi MV, Chettri D, Verma AK (2020) Human microbiome: an academic update on human body site specific surveillance and its possible role. Arch Microbiol 202:2147–2167. https://doi.org/10.1007/s00203-020-01931-x
Ragonnaud E, Biragyn A (2021) Gut microbiota as the key controllers of “healthy” aging of elderly people. Immun Ageing 18:2. https://doi.org/10.1186/s12979-020-00213-w
Wall R, Ross RP, Ryan CA, Hussey S, Murphy B, Fitzgerald GF et al (2009) Role of gut microbiota in early infant development. Clin Med Insights Pediatr 3:S2008. https://doi.org/10.4137/CMPed.S2008
Valeur J, Berstad A (2010) Colonic fermentation: a neglected topic in human physiology education. Adv Physiol Educ 34:22–22. https://doi.org/10.1152/advan.00103.2009
Shanahan F (2013) The colonic microbiota in health and disease. Curr Opin Gastroenterol 29:49–54. https://doi.org/10.1097/MOG.0b013e32835a3493
Rodes L, Coussa-Charley M, Marinescu D, Paul A, Fakhoury M, Abbasi S et al (2013) Design of a novel gut bacterial adhesion model for probiotic applications. Artif Cells Nanomed Biotechnol 41:116–124. https://doi.org/10.3109/10731199.2012.712047
Venema K, Van den Abbeele P (2013) Experimental models of the gut microbiome. Best Pract Res Clin Gastroenterol 27:115–126. https://doi.org/10.1016/j.bpg.2013.03.002
Martin G, Kolida S, Marchesi JR, Want E, Sidaway JE, Swann JR (2018) In vitro modeling of bile acid processing by the human fecal microbiota. Front Microbiol 9:1153. https://doi.org/10.3389/fmicb.2018.01153
Payne AN, Zihler A, Chassard C, Lacroix C (2012) Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol 30:17–25. https://doi.org/10.1016/j.tibtech.2011.06.011
Barros L, Retamal C, Torres H, Zúñiga RN, Troncoso E (2016) Development of an in vitro mechanical gastric system (IMGS) with realistic peristalsis to assess lipid digestibility. Food Res Int 90:216–225. https://doi.org/10.1016/j.foodres.2016.10.049
Liu W, Fu D, Zhang X, Chai J, Tian S, Han J (2019) Development and validation of a new artificial gastric digestive system. Food Res Int 122:183–190. https://doi.org/10.1016/j.foodres.2019.04.015
Li Y, Fortner L, Kong F (2019) Development of a Gastric Simulation Model (GSM) incorporating gastric geometry and peristalsis for food digestion study. Food Res Int 125:108598. https://doi.org/10.1016/j.foodres.2019.108598
Blutt SE, Crawford SE, Ramani S, Zou WY, Estes MK (2018) Engineered human gastrointestinal cultures to study the microbiome and infectious diseases. Cell Mol Gastroenterol Hepatol 5:241–251. https://doi.org/10.1016/j.jcmgh.2017.12.001
Min S, Kim S, Cho SW (2020) Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches. Exp Mol Med 52:227–237. https://doi.org/10.1038/s12276-020-0386-0
Costa J, Ahluwalia A (2019) Advances and current challenges in intestinal in vitro model engineering: a digest. Front Bioeng Biotechnol 7:144. https://doi.org/10.3389/fbioe.2019.00144
Bricks T, Paullier P, Legendre A, Fleury MJ, Zeller P, Merlier F et al (2014) Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Toxicol In-vitro 28:885–895. https://doi.org/10.1016/j.tiv.2014.02.005
Sung JH, Yu J, Luo D, Shuler ML, March JC (2011) Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip 11:389–392. https://doi.org/10.1039/C0LC00273A
Shim KY, Lee D, Han J, Nguyen NT, Park S, Sung JH (2017) Microfluidic gut-on-a-chip with three-dimensional villi structure. Biomed Microdevices 19:1–10. https://doi.org/10.1007/s10544-017-0179-y
Kim HJ, Huh D, Hamilton G, Ingber DE (2012) Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12:2165–2174. https://doi.org/10.1039/c2lc40074j
Waclawiková B, Codutti A, Alim K, El Aidy S (2022) Gut microbiota-motility interregulation: insights from in vivo, ex vivo and in silico studies. Gut Microbes 14:1997296. https://doi.org/10.1080/19490976.2021.1997296
Molina Ortiz JP, McClure DD, Shanahan ER, Dehghani F, Holmes AJ, Read MN (2021) Enabling rational gut microbiome manipulations by understanding gut ecology through experimentally-evidenced in silico models. Gut Microbes 13:1965698. https://doi.org/10.1080/19490976.2021.1965698
Sen P, Orešič M (2019) Metabolic modeling of human gut microbiota on a genome scale: an overview. Metabolites 9:22. https://doi.org/10.3390/metabo9020022
Henson MA (2021) Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling. Eng Life Sci 21:489–501. https://doi.org/10.1002/elsc.202100003
Mandalari G, Adel-Patient K, Barkholt V, Baro C, Bennett L, Bublin M et al (2009) In vitro digestibility of β-casein and β-lactoglobulin under simulated human gastric and duodenal conditions: a multi-laboratory evaluation. Regul Toxicol Pharmacol 55:372–381. https://doi.org/10.1016/j.yrtph.2009.08.010
Yeo S, Lee S, Park H, Shin H, Holzapfel W, Huh CS (2016) Development of putative probiotics as feed additives: validation in a porcine-specific gastrointestinal tract model. Appl Microbiol Biotechnol 100:10043–10054. https://doi.org/10.1007/s00253-016-7812-1
Cichoke AJ (1999) The complete book of enzyme therapy. Penguin, Chapter, p 2. https://patentscope.wipo.int/search/en/detail.jsf?10.1007/s12602-023-10052-ydocId=WO2007010238. Accessed 14 Nov 2022
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The authors gratefully acknowledge the support of Mr. V. L. Rathi and Mr. M. Kabra at the Advanced Enzyme Technologies Limited, India.
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Y. D.: formal analysis, writing including review and editing, and writing of original draft. K. K. and N. B.: writing including review and editing. D. S.: review. J. J. A.: conceptualization and writing including review and editing. All authors read and approved the final version of the manuscript.
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Y. D., K. K., N. B., D. S. and J. J. A. were employed by the Advanced Enzyme Technologies Limited. This does not alter our adherence to journal policies on sharing data and materials.
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Dixit, Y., Kanojiya, K., Bhingardeve, N. et al. In Vitro Human Gastrointestinal Tract Simulation Systems: A Panoramic Review. Probiotics & Antimicro. Prot. 16, 501–518 (2024). https://doi.org/10.1007/s12602-023-10052-y
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DOI: https://doi.org/10.1007/s12602-023-10052-y