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gut on a chip

Lauren D Wu, L Renee Ruhaak, Carlito B Lebrilla
Human milk oligosaccharides (HMOs) are a highly abundant constituent in human milk, and its protective and prebiotic properties have attracted considerable attention. HMOs have been shown to directly and indirectly benefit the overall health of the infant due to a number of functions including serving as a beneficial food for gut bacteria, block to pathogens, and aiding in brain development. Researchers are currently exploring whether these structures may act as possible disease and nutrition biomarkers. Because of this, rapid-throughput methods are desired to investigate biological activity in large patient sets...
2017: Methods in Molecular Biology
Hyun Jung Kim, Jaewon Lee, Jin-Ha Choi, Anthony Bahinski, Donald E Ingber
Here, we describe a protocol to perform long-term co-culture of multi-species human gut microbiome with microengineered intestinal villi in a human gut-on-a-chip microphysiological device. We recapitulate the intestinal lumen-capillary tissue interface in a microfluidic device, where physiological mechanical deformations and fluid shear flow are constantly applied to mimic peristalsis. In the lumen microchannel, human intestinal epithelial Caco-2 cells are cultured to form a 'germ-free' villus epithelium and regenerate small intestinal villi...
2016: Journal of Visualized Experiments: JoVE
J Salcedo, S A Frese, D A Mills, D Barile
The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA)...
October 2016: Journal of Dairy Science
Jaewon Lee, Jin-Ha Choi, Hyun Jung Kim
No abstract text is available yet for this article.
August 2016: Expert Review of Gastroenterology & Hepatology
W Rodney Cooper, David R Horton, Thomas R Unruh, Stephen F Garczynski
Potato psyllid, Bactericera cockerelli (Šulc) (Hemiptera: Triozidae), is a key pest of potato (Solanum tuberosum L., Solanales: Solanaceae) and a vector of "Candidatus Liberibacter solanacearum," the pathogen associated with zebra chip disease. In addition to its presence on cultivated crops, the psyllid regularly occurs on numerous uncultivated annual and perennial species within the Solanaceae. A better understanding of landscape-level ecology of B. cockerelli would substantially improve our ability to predict which potato fields are most likely to be colonized by infected psyllids...
August 2016: Environmental Entomology
Lingli Zhang, Chunlong Mu, Xiangyu He, Yong Su, Shengyong Mao, Jing Zhang, Hauke Smidt, Weiyun Zhu
This study aimed to investigate the effects of dietary fibre sources on the gut microbiota in suckling piglets, and to test the hypothesis that a moderate increase of dietary fibre may affect the gut microbiota during the suckling period. Suckling piglets were fed different fibre-containing diets or a control diet from postnatal day 7 to 22. Digesta samples from cecum, proximal colon and distal colon were used for Pig Intestinal Tract Chip analysis. The data showed that the effects of fibre-containing diet on the gut microbiota differed in the fibre source and gut location...
July 2016: FEMS Microbiology Letters
Joana F S Pereira, Nikhil T Awatade, Cláudia A Loureiro, Paulo Matos, Margarida D Amaral, Peter Jordan
Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffold-free or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology...
November 2016: Cellular and Molecular Life Sciences: CMLS
Pia Kiilerich, Lene Secher Myrmel, Even Fjære, Qin Hao, Floor Hugenholtz, Si Brask Sonne, Muriel Derrien, Lone Møller Pedersen, Rasmus Koefoed Petersen, Alicja Mortensen, Tine Rask Licht, Maria Unni Rømer, Ulla Birgitte Vogel, Linn Jeanette Waagbø, Natasa Giallourou, Qiang Feng, Liang Xiao, Chuan Liu, Bjørn Liaset, Michiel Kleerebezem, Jun Wang, Lise Madsen, Karsten Kristiansen
Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice...
June 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Qiongyou Liu, Yang Zhang, Boyang Shi, Huijie Lu, Lihong Zhang, Weimin Zhang
FOXO3 has been shown to be a critical transcription factor for folliculogenesis in mammals, while the information on its roles in reproduction of nonmammalian vertebrates remains scarce. In this study, two foxo3 homologs, namely foxo3a and foxo3b, were identified in a teleost, the orange-spotted grouper Epinephelus coioides. foxo3a was mainly expressed in the central nervous system, ovary, and gut whereas foxo3b was expressed ubiquitously in tissues examined. In contrast to the dominant expression of mammalian FOXO3 in germ cells but barely detectable in ovarian follicular cells, immunoreactive Foxo3a and Foxo3b were identified both in the ovarian germ cells and follicular cells...
May 2016: Journal of Molecular Endocrinology
Aleksander Skardal, Mahesh Devarasetty, Steven Forsythe, Anthony Atala, Shay Soker
Current animal and 2-D cell culture models employed in metastasis research and drug discovery remain poor mimics of human cancer physiology. Here we describe a "metastasis-on-a-chip" system allowing real time tracking of fluorescent colon cancer cells migrating from hydrogel-fabricated gut constructs to downstream liver constructs within a circulatory fluidic device system that responds to environmental manipulation and drug treatment. Devices consist of two chambers in which gut and liver constructs are housed independently, but are connected in series via circulating fluid flow...
September 2016: Biotechnology and Bioengineering
Hyun Jung Kim, Hu Li, James J Collins, Donald E Ingber
A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria...
January 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
J M Cicero, T W Fisher, J K Brown
The potato psyllid Bactericera cockerelli is implicated as the vector of the causal agent of zebra chip of potato and vein-greening of tomato diseases. Until now, visual identification of bacteria in the genus 'Candidatus Liberibacter' has relied on direct imaging by light and electron microscopy without labeling, or with whole-organ fluorescence labeling only. In this study, aldehyde fixative followed by a coagulant fixative, was used to process adult psyllids for transmission electron microscopy (TEM) colloidal gold in situ hybridization experiments...
February 2016: Phytopathology
Manuel Corpas, Willy Valdivia-Granda, Nazareth Torres, Bastian Greshake, Alain Coletta, Alexej Knaus, Andrew P Harrison, Mike Cariaso, Federico Moran, Fiona Nielsen, Daniel Swan, David Y Weiss Solís, Peter Krawitz, Frank Schacherer, Peter Schols, Huangming Yang, Pascal Borry, Gustavo Glusman, Peter N Robinson
BACKGROUND: We describe the pioneering experience of a Spanish family pursuing the goal of understanding their own personal genetic data to the fullest possible extent using Direct to Consumer (DTC) tests. With full informed consent from the Corpas family, all genotype, exome and metagenome data from members of this family, are publicly available under a public domain Creative Commons 0 (CC0) license waiver. All scientists or companies analysing these data ("the Corpasome") were invited to return results to the family...
2015: BMC Genomics
Yuichi Morozumi, Fayçal Boussouar, Minjia Tan, Apirat Chaikuad, Mahya Jamshidikia, Gozde Colak, Huang He, Litong Nie, Carlo Petosa, Maud de Dieuleveult, Sandrine Curtet, Anne-Laure Vitte, Clothilde Rabatel, Alexandra Debernardi, François-Loïc Cosset, Els Verhoeyen, Anouk Emadali, Norbert Schweifer, Davide Gianni, Marta Gut, Philippe Guardiola, Sophie Rousseaux, Matthieu Gérard, Stefan Knapp, Yingming Zhao, Saadi Khochbin
Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication, and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome...
August 2016: Journal of Molecular Cell Biology
Norio Kamemura, Miwa Takashima, Hideaki Morita, Kenji Matsumoto, Hirohisa Saito, Hiroshi Kido
BACKGROUND AND AIMS: Measurement of secretory immunoglobulin A (SIgA) level is important to monitor various disease conditions. However SIgA in gut mucosa is degraded by pancreatic proteases and proteolytic enzymes from enteric microbiota. Currently, there is no reliable quantitation method that measures allergen-specific SIgA levels in stool of neonates, infants and toddlers. METHODS: Allergen-specific SIgA levels in stool of 10 healthy neonates, infants and toddlers aged 0 to 36 months were measured by our new allergen microarray with densely carboxylated arms on a glass slide chip...
2015: Journal of Medical Investigation: JMI
Sercan Karav, Annabelle Le Parc, Juliana Maria Leite Nobrega de Moura Bell, Camille Rouquié, David A Mills, Daniela Barile, David E Block
EndoBI-1 is a recently isolated endo-β-N-acetylglucosaminidase, which cleaves the N-N'-diacetyl chitobiose moiety found in the N-glycan core of high mannose, hybrid and complex N-glycans. These N-glycans have selective prebiotic activity for a key infant gut microbe, Bifidobacterium longum subsp. infantis. The broad specificity of EndoBI-1 suggests the enzyme may be useful for many applications, particularly for deglycosylating milk glycoproteins in dairy processing. To facilitate its commercial use, we determined kinetic parameters for EndoBI-1 on the model substrates ribonuclease B and bovine lactoferrin, as well as on concentrated bovine colostrum whey...
September 2015: Enzyme and Microbial Technology
Ahmad Al-Saffar, André Nogueira da Costa, Annie Delaunois, Derek J Leishman, Louise Marks, Marie-Luce Rosseels, J-P Valentin
Although the basic structure of the gastrointestinal tract (GIT) is similar across species, there are significant differences in the anatomy, physiology, and biochemistry between humans and laboratory animals, which should be taken into account when conducting a gastrointestinal (GI) assessment. Historically, the percentage of cases of drug attrition associated with GI-related adverse effects is small; however, this incidence has increased over the last few years. Drug-related GI effects are very diverse, usually functional in nature, and not limited to a single pharmacological class...
2015: Handbook of Experimental Pharmacology
S Apewokin, J A Goodwin, J Y Lee, S W Erickson, N Sanathkumar, V R Raj, D Zhou, K D McKelvey, O Stephens, E A Coleman
BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such as Clostridium difficile are not well defined. We performed a genome-wide association study (GWAS) to investigate clinical and genetic factors associated with development of LGAE...
August 2015: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Xiaolong Luo, Chen-Yu Tsao, Hsuan-Chen Wu, David N Quan, Gregory F Payne, Gary W Rubloff, William E Bentley
The human gut is over a meter in length, liquid residence times span several hours. Recapitulating the human gut microbiome "on chip" holds promise to revolutionize therapeutic strategies for a variety of diseases, as well as for maintaining homeostasis in healthy individuals. A more refined understanding of bacterial-bacterial and bacterial-epithelial cell signalling is envisioned and such a device is a key enabler. Indeed, significant advances in the study of bacterial cell-cell signalling have been reported, including at length and time scales of the cells and their responses...
April 21, 2015: Lab on a Chip
Jean-Marc Navarro, Aurore Touzart, Lydie C Pradel, Marie Loosveld, Myriam Koubi, Romain Fenouil, Sandrine Le Noir, Muhammad Ahmad Maqbool, Ester Morgado, Claude Gregoire, Sebastien Jaeger, Emilie Mamessier, Charles Pignon, Salima Hacein-Bey-Abina, Bernard Malissen, Marta Gut, Ivo G Gut, Hervé Dombret, Elizabeth A Macintyre, Steven J Howe, H Bobby Gaspar, Adrian J Thrasher, Norbert Ifrah, Dominique Payet-Bornet, Estelle Duprez, Jean-Christophe Andrau, Vahid Asnafi, Bertrand Nadel
T-cell acute lymphoblastic leukaemias (T-ALL) are aggressive malignant proliferations characterized by high relapse rates and great genetic heterogeneity. TAL1 is amongst the most frequently deregulated oncogenes. Yet, over half of the TAL1(+) cases lack TAL1 lesions, suggesting unrecognized (epi)genetic deregulation mechanisms. Here we show that TAL1 is normally silenced in the T-cell lineage, and that the polycomb H3K27me3-repressive mark is focally diminished in TAL1(+) T-ALLs. Sequencing reveals that >20% of monoallelic TAL1(+) patients without previously known alterations display microinsertions or RAG1/2-mediated episomal reintegration in a single site 5' to TAL1...
2015: Nature Communications
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