https://orcid.org/0000-0003-1631-7451
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ABSTRACT
Enhanced intestinal permeability is a pervasive issue in modern medicine, with implications demonstrably associated with significant health consequences such as sepsis, multiorgan failure, and death. Key issues involve the trigger mechanisms that could compromise intestinal integrity and increase local permeability allowing the passage of larger, potentially dangerous molecules. Heat stress, whether exertional or environmental, may modulate intestinal permeability and begs interesting questions in the context of global climate change, increasing population vulnerabilities, and public health. Emerging evidence indicates that intestinal leakage of digestive enzymes and associated cell dysfunctions––a process referred to as autodigestion––may play a critical role in systemic physiological damage within the body. This increased permeability is exacerbated in the presence of elevated core temperatures. We employed Latent Dirichlet Allocation (LDA) topic modeling methods to analyze the relationship between heat stress and the nascent theory of autodigestion in a systematic, quantifiable, and unbiased manner. From a corpus of 11,233 scientific articles across four relevant scientific journals (Gut, Shock, Temperature, Gastroenterology), it was found that over 1,000 documents expressed a relationship between intestine, enhanced permeability, core temperature, and heat stress. The association has grown stronger in recent years, as heat stress and potential autodigestion are investigated in tandem, yet still by a limited number of specific research studies. Such findings justify the design of future studies to critically test novel interventions against digestive enzymes permeating the intestinal tract, especially the small intestine.
Abbreviations
| AD – | = | Autodigestion |
| BMI – | = | Body Mass Index |
| CNS – | = | Central Nervous System |
| ECOC – | = | Error Correcting Output Codes |
| EHS – | = | Exertional Heat Stroke |
| EIGS – | = | Exercise Induced Gastrointestinal Syndrome |
| EXC – | = | Exercise Control |
| Exh – | = | Exhaustion |
| GloVe – | = | Global Word Vectorization |
| HS – | = | Heat Stress(ed) |
| IEC-6 – | = | Intestinal Epithelial Cell |
| I-FABP – | = | Intestinal Fatty Acid Binding Protein |
| IL-1 – | = | Interleukin 1 |
| IL-1β – | = | Interleukin 1 Beta |
| IL-6 – | = | Interleukin 6 |
| IL-10 – | = | Interleukin 10 |
| IL-12p40 – | = | Interleukin 12 subunit p40 |
| LDA – | = | Latent Dirichlet Allocation |
| LPS – | = | Lipopolysaccharide |
| L/R – | = | Lactulose-to-Rhamnose |
| LSA – | = | Latent Semantic Analysis |
| PAR1 – | = | Protease-Activated Receptor |
| SIRS – | = | Systemic Inflammatory Syndrome |
| SM – | = | Supplemental Material |
| SVM – | = | Support Vector Machines |
| Tc – | = | Core Temperature |
| TF-IDF – | = | Term-Frequency Inverse Document-Frequency |
| TLR-4 – | = | Toll-Like Receptors 4 |
| TNF – | = | Tumor Necrosis Factor |
| TR – | = | Trained |
| UT – | = | Untrained |
| 99mTc-DTPA – | = | 99mTc-diethylenetriaminepentaacetic |
Disclosure
AAF, AZ, and JKV declare no conflict of interest. GWSS owns stock in Leading Biosciences, Inc., a company to develop shock treatments.
Supplementary material
Supplemental data for this article can be accessed here
Data availability statement
Please contact Anthony A. Fung ([email protected]) for the corpus code, which is comprised of commercial MATLAB toolboxes, as well as network diagrams made in Gephi.
Additional information
Notes on contributors
Anthony A. Fung
Anthony A. Fung is PhD student in the department of Bioengineering at the University of California, San Diego. His research is focused on biomedical applications of Raman Scattering Microscopy in ageing and metabolism. Anthony is also developing novel and user-friendly tools for scientists and clinicians to adopt Raman technology at all stages of research and development. He is a founding member of the Design For America studio at UC San Diego, and former team lead of award-winning Global TIES projects.
Andy Zhou
Andy Zhou is a Master’s student in the Department of Electrical and Computer Engineering at Carnegie Mellon University. His technical interests include machine learning, distributed systems, and cloud computing.
Jennifer K. Vanos
Dr. Jennifer Vanos holds an interdisciplinary appointment studying climate and human health in the School of Sustainability at Arizona State University. As a human biometeorologist, she works to strengthen the understanding and practice surrounding how we protect people from extreme heat in a world impacted by climate change. Her work on extreme heat addresses risks and challenges within varying vulnerable populations, including children, athletes, and outdoor workers. She approaches her work using various measurement and modeling tools and frameworks across spatiotemporal scales. She is a member of ASU’s Urban Climate Research Center and currently Chair of the American Meteorological Society’s Board on Environment & Health. She previously worked at UC San Diego, Texas Tech University, Health Canada, and the University of Guelph.
Geert W. Schmid-Schönbein
Geert W. Schmid-Schönbein is Distinguished Professor and former Chair of the Department of Bioengineering at the University of California in San Diego which is where he received his graduate degree. He conducted postdoctoral research at Columbia University after which he returned to the University of California in San Diego. His research is focused on blood flow in the microcirculation, cell mechanics and mechanotransduction with application to human disease. His team uncovered a previously unknown mechanism for inflammation due to “Auto-digestion”. He is Founding Member of American Institute of Medical and Biological Engineering, former President of the Biomedical Engineering Society, the Microcirculatory Society and the North American Society of Biorheology. He was Chair of the World Council for Biomechanics and the US National Committee for Biomechanics and is a member of the National Academy of Engineering.