Publications
Browse peer-reviewed literature, posters, webinars, blog articles, and more showing how we and others are using RepliGut Systems to support discovery.
2024
Debad, Susan; Allen, David; Bandele, Omari; Bishop, Colin; Blaylock, Michaela; Brown, Paul; Bunger, Maureen K.; Co, Julia Y.; Crosby, Lynn; Daniel, Amber B.; Ferguson, Steve S.; Ford, Kevin; da Costa, Gonçalo Gamboa; Gilchrist, Kristin H.; Grogg, Matthew W.; Gwinn, Maureen; Hartung, Thomas; Hogan, Simon P.; Jeong, Ye Eun; Kass, George E. N.; Kenyon, Elaina; Kleinstreuer, Nicole C.; Kujala, Ville; Lundquist, Patrik; Matheson, Joanna; McCullough, Shaun D.; Melton-Celsa, Angela; Musser, Steven; Oh, Ilung; Oyetade, Oluwakemi B.; Patil, Sarita U.; Petersen, Elijah J.; Sadrieh, Nakissa; Sayes, Christie M.; Scruggs, Benjamin S.; Tan, Yu-Mei; Thelin, Bill; Nelson, M. Tyler; Tarazona, José V.; Wambaugh, John F.; Yang, Jun-Young; Yu, Changwoo; Fitzpatrick, Suzanne
Trust your gut: Establishing confidence in gastrointestinal models – An overview of the state of the science and contexts of use Journal Article
In: ALTEX, vol. 41, no. 3, pp. 402–424, 2024, ISSN: 1868-8551.
Abstract | Links | BibTeX | Tags: Adverse events, Co-culture model, Enteroendocrine Cells, epithelial barrier, Gut barrier function, Gut liver microphysiological system, in vitro models, intestinal barrier, microphysiological system, microphysiological systems, organ-on-chips
@article{debad_trust_2024,
title = {Trust your gut: Establishing confidence in gastrointestinal models – An overview of the state of the science and contexts of use},
author = {Susan Debad and David Allen and Omari Bandele and Colin Bishop and Michaela Blaylock and Paul Brown and Maureen K. Bunger and Julia Y. Co and Lynn Crosby and Amber B. Daniel and Steve S. Ferguson and Kevin Ford and Gonçalo Gamboa da Costa and Kristin H. Gilchrist and Matthew W. Grogg and Maureen Gwinn and Thomas Hartung and Simon P. Hogan and Ye Eun Jeong and George E. N. Kass and Elaina Kenyon and Nicole C. Kleinstreuer and Ville Kujala and Patrik Lundquist and Joanna Matheson and Shaun D. McCullough and Angela Melton-Celsa and Steven Musser and Ilung Oh and Oluwakemi B. Oyetade and Sarita U. Patil and Elijah J. Petersen and Nakissa Sadrieh and Christie M. Sayes and Benjamin S. Scruggs and Yu-Mei Tan and Bill Thelin and M. Tyler Nelson and José V. Tarazona and John F. Wambaugh and Jun-Young Yang and Changwoo Yu and Suzanne Fitzpatrick},
url = {https://altex.org/index.php/altex/article/view/2787},
doi = {10.14573/altex.2403261},
issn = {1868-8551},
year = {2024},
date = {2024-07-16},
urldate = {2024-07-16},
journal = {ALTEX},
volume = {41},
number = {3},
pages = {402–424},
abstract = {The webinar series and workshop titled “Trust Your Gut: Establishing Confidence in Gastrointestinal Models – An Overview of the State of the Science and Contexts of Use” was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.
Plain language summaryNon-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from different countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.},
keywords = {Adverse events, Co-culture model, Enteroendocrine Cells, epithelial barrier, Gut barrier function, Gut liver microphysiological system, in vitro models, intestinal barrier, microphysiological system, microphysiological systems, organ-on-chips},
pubstate = {published},
tppubtype = {article}
}
The webinar series and workshop titled “Trust Your Gut: Establishing Confidence in Gastrointestinal Models – An Overview of the State of the Science and Contexts of Use” was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.
Plain language summaryNon-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from different countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.
Plain language summaryNon-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from different countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.
2022
Bolster, Doug; Chae, Lee; van Klinken, Jan-Willem; Kalgaonkar, Swati
Impact of selected novel plant bioactives on improvement of impaired gut barrier function using human primary cell intestinal epithelium: Journal Article
In: Journal of Food Bioactives, vol. 20, 2022, ISSN: 2637-8779.
Abstract | Links | BibTeX | Tags: Bioactives, Gut barrier function, Gut permeability, Hepatic nuclear factor 4α, In vitro model, inflammatory bowel disease, intestinal barrier, N-Trans-caffeoyltyramine, N-Trans-feruloyltyramine
@article{bolster_impact_2022,
title = {Impact of selected novel plant bioactives on improvement of impaired gut barrier function using human primary cell intestinal epithelium:},
author = {Doug Bolster and Lee Chae and Jan-Willem van Klinken and Swati Kalgaonkar},
url = {http://www.isnff-jfb.com/index.php/JFB/article/view/301},
doi = {10.31665/JFB.2022.18324},
issn = {2637-8779},
year = {2022},
date = {2022-12-30},
urldate = {2022-12-30},
journal = {Journal of Food Bioactives},
volume = {20},
abstract = {Gut barrier function is compromised in the obese state. The N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT), two naturally occurring bioactive compounds in hemp hulls, identified using in silico approaches, have the potential to improve gut barrier function and their effects were studied here in vitro. Proliferative human transverse colon epithelial cells were plated and co-cultured with tumor necrosis factor (TNF) along with NCT, NFT or NCT/NFT (2.2 ratio) post-differentiation, over a 48-hour period to induce inflammation and to observe the effects of NCT and NFT. A decrease in transepithelial electrical resistance (TEER) and increase in the intestinal permeability were observed with increased addition of TNF. Co-administration of NCT and NFT demonstrated a dose-dependent and statistically significant reversal of impaired TEER and intestinal permeability. NCT and NFT demonstrated a physiologically relevant reversal of impaired gut barrier function in the setting of inflammation via significant improvement in TEER and percent permeability.},
keywords = {Bioactives, Gut barrier function, Gut permeability, Hepatic nuclear factor 4α, In vitro model, inflammatory bowel disease, intestinal barrier, N-Trans-caffeoyltyramine, N-Trans-feruloyltyramine},
pubstate = {published},
tppubtype = {article}
}
Gut barrier function is compromised in the obese state. The N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT), two naturally occurring bioactive compounds in hemp hulls, identified using in silico approaches, have the potential to improve gut barrier function and their effects were studied here in vitro. Proliferative human transverse colon epithelial cells were plated and co-cultured with tumor necrosis factor (TNF) along with NCT, NFT or NCT/NFT (2.2 ratio) post-differentiation, over a 48-hour period to induce inflammation and to observe the effects of NCT and NFT. A decrease in transepithelial electrical resistance (TEER) and increase in the intestinal permeability were observed with increased addition of TNF. Co-administration of NCT and NFT demonstrated a dose-dependent and statistically significant reversal of impaired TEER and intestinal permeability. NCT and NFT demonstrated a physiologically relevant reversal of impaired gut barrier function in the setting of inflammation via significant improvement in TEER and percent permeability.
Burclaff, Joseph; Bliton, R. Jarrett; Breau, Keith A.; Ok, Meryem T.; Gomez-Martinez, Ismael; Ranek, Jolene S.; Bhatt, Aadra P.; Purvis, Jeremy E.; Woosley, John T.; Magness, Scott T.
A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics Journal Article
In: Cell Mol Gastroenterol Hepatol, vol. 13, no. 5, pp. 1554–1589, 2022, ISSN: 2352-345X.
Abstract | Links | BibTeX | Tags: Differentiate Cell Lineage, Enterochromaffin Cells, Enterocytes, Enteroendocrine Cells, Gut barrier function, Intestinal Epithelial Cells
@article{burclaff_proximal–distal_2022,
title = {A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics},
author = {Joseph Burclaff and R. Jarrett Bliton and Keith A. Breau and Meryem T. Ok and Ismael Gomez-Martinez and Jolene S. Ranek and Aadra P. Bhatt and Jeremy E. Purvis and John T. Woosley and Scott T. Magness},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043569/},
doi = {10.1016/j.jcmgh.2022.02.007},
issn = {2352-345X},
year = {2022},
date = {2022-02-15},
urldate = {2022-02-15},
journal = {Cell Mol Gastroenterol Hepatol},
volume = {13},
number = {5},
pages = {1554–1589},
abstract = {Background & Aims
Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings.
Methods
A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses.
Conclusions
Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.},
keywords = {Differentiate Cell Lineage, Enterochromaffin Cells, Enterocytes, Enteroendocrine Cells, Gut barrier function, Intestinal Epithelial Cells},
pubstate = {published},
tppubtype = {article}
}
Background & Aims
Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings.
Methods
A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses.
Conclusions
Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings.
Methods
A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses.
Conclusions
Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.