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UCSD Researchers Develop a Wearable Skin Patch That Monitors Blood Pressure, Glucose Levels, and Other Biomarkers in Human Sweat

Skin patch technologies could enable clinical laboratories to monitor patients’ vitals and report to medical professionals in real time

Pathologists and clinical laboratory leaders have read many Dark Daily ebriefings on the development of skin patches over the years that do everything from monitoring fatigue in the military to being a complete lab-on-skin technology. Now, researchers at the University of California San Diego (UCSD) have developed a wearable patch that can monitor cardiovascular signals and other various biochemical levels in the body simultaneously.

The researchers believe there is enormous potential for such a patch in helping patients monitor conditions such as hypertension or diabetes. They also foresee a scenario where the patch could be used in settings where vitals must be constantly monitored. They hope to develop future versions of the patch that can detect more biomarkers within the body.

“This type of wearable would be very helpful for people with underlying medical conditions to monitor their own health on a regular basis,” Lu Yin, a PhD student and co-first author of the study, told New Atlas. “It would also serve as a great tool for remote patient monitoring, especially during the COVID-19 pandemic when people are minimizing in-person visits to the clinic,” she added.

The UCSD researchers published the results of their study in the peer-reviewed journal Nature Biomedical Engineering, titled, “An Epidermal Patch for the Simultaneous Monitoring of Haemodynamic and Metabolic Biomarkers.”

Combining Precision Medicine with Telehealth and the Internet of Things

About the size of a postage stamp and consisting of stretchy polymers that conform to the skin, the UCSD patch monitors blood pressure and contains sensors that measure different biochemical levels in the body, such as:

The sensors are carefully arranged on the patch to eliminate interference between the signals, noted a UCSD press release.

Skin patch monitoring device

In their published research, the UCSD researchers wrote of their new skin patch monitoring device, “Intertwined with concepts of telehealth, the internet of medical things, and precision medicine, wearable sensors offer features to actively and remotely monitor physiological parameters. Wearable sensors can generate data continuously without causing any discomfort or interruptions to daily activity, thus enhancing the self-monitoring compliance of the wearer, and improving the quality of patient care.” (Photo copyright: University of California San Diego.)

“Each sensor provides a separate picture of a physical or chemical change. Integrating them all in one wearable patch allows us to stitch those different pictures together to get a more comprehensive overview of what’s going on in our bodies,” said Sheng Xu, PhD, Principle Investigator, Xu Research Group at UCSD, Assistant Professor in the Department of NanoEngineering Department, and a co-first author of the study, in the press release.

The UCSD researchers developed their skin patch to monitor specific biomarkers that can affect blood pressure.

“Let’s say you are monitoring your blood pressure and you see spikes during the day and think that something is wrong,” co-first author Juliane Sempionatto, PhD, a postdoctoral researcher at California Institute of Technology (Caltech) and co-first author of the study, told New Atlas. “But a biomarker reading could tell you if those spikes were due to an intake of alcohol or caffeine. This combination of sensors can give you that type of information,” she added.

The blood pressure sensor sits near the center of the patch and consists of a set of small transducers welded to the patch via a conductive link. Voltage applied to the transducers send ultrasound waves through the body which bounce off arteries and create echoes that are detected by the sensor and converted into an accurate blood pressure reading.

The chemical sensor releases the drug pilocarpine into the skin to induce sweat and then measures the chemicals contained in the sweat to provide readings of certain biochemical levels.

The glucose sensor located in the patch emits a mild electrical current to the body that stimulates the release of interstitial fluid and then reads the glucose level in that fluid.

Joseph Wang, D.Sc

“The novelty here is that we take completely different sensors and merge them together on a single small platform as small as a stamp,” Joseph Wang, D.Sc, SAIC Endowed Chair, Distinguished Professor of NanoEngineering, Director of the Center for Wearable Sensors at UCSD, and co-author of the study told New Atlas. “We can collect so much information with this one wearable and do so in a non-invasive way, without causing discomfort or interruptions to daily activity.” (Photo copyright: University of Southern California San Diego.)

Skin Patch Measurements Closely Match Those of Traditional Devices

Test subjects wore the patch on their neck while performing various combinations of the following tasks:

  • exercising on a stationary bicycle,
  • eating a high-sugar meal,
  • drinking an alcoholic beverage, and
  • drinking a caffeinated beverage.

The results of the measurements taken from the patch closely matched measurements collected by traditional monitoring devices such as a:

For now, the patch must be connected to an external power source which transmits the reading to a counter-top machine, but the researchers hope to create a wireless version in the future.

“There are opportunities to monitor other biomarkers associated with various diseases,” Sempionatto said in the UCSD press release. “We are looking to add more clinical value to this device.”

Other Similar Skin Patch Monitoring Technologies

Though an important breakthrough, the UCSD’s device is not the first skin patch monitor to be developed.

In “Researchers at Washington University in St. Louis Use Microneedle Patch with Fluorescent Nanolabels to Detect Biomarkers in Skin’s Interstitial Fluid,” Dark Daily reported on a microneedle patch designed by researchers at the McKelvey School of Engineering at Washington University in St. Louis which adheres to the skin like a bandage and could possibly serve as a pain-free way to take blood samples without the need for a venipuncture or needle stick.

And in “In the Field of Nano-Scale Diagnostics, Many Researchers Are Developing ‘Lab-on-Skin’ Technologies That Can Monitor Many Clinical Laboratory Biomarkers,” we covered development of a wearable “lab-on-skin” technology that noninvasively measure a variety of physiological data, including: blood pressure, glucose/potassium/sodium levels, hydration, oxygenation, and more.

Multiple research and clinical studies are underway that hope to prove the accuracy and safety of wearable devices at detecting and monitoring certain health conditions. It’s a worthy goal.

Skin patches, such as the one created at UCSD, could enable clinical laboratories to provide value-added service to medical professionals and patients alike. Medical labs could potentially monitor skin patch readings in real-time and notify physicians and patients of changes in biomarkers that require attention.

Further, as this technology is developed, it will likely find a ready market with the latest generation of consumers who are more willing than previous generations to buy their own diagnostic tests for home use. These “next-generation” healthcare consumers have demonstrated their willingness to use Apple watches, Fitbits, and similar wearable devices to monitor their condition during exercise and other health metrics.

Pathologists and clinical laboratory managers should not overlook the potential for robust consumer demand to accelerate development and market adoption of such skin patches.

JP Schlingman

Related Information

First-of-a-kind Patch Tracks Multiple Biochemicals and Blood Pressure

An Epidermal Patch for the Simultaneous Monitoring of Haemodynamic and Metabolic Biomarkers

New Skin Patch Brings Us Closer to Wearable, All-In-One Health Monitor

Researchers at Washington University in St. Louis Use Microneedle Patch with Fluorescent Nanolabels to Detect Biomarkers in Skin’s Interstitial Fluid

In the Field of Nano-Scale Diagnostics, Many Researchers Are Developing ‘Lab-on-Skin’ Technologies That Can Monitor Many Clinical Laboratory Biomarkers

Lab-on-a-Chip Diagnostics: When Will Clinical Laboratories See the Revolution?

Lithuanian Researchers Develop Novel Noninvasive Method for Diagnosing Melanoma That Has Greater than 90% Accuracy

Computer-aided diagnostic system combines optical dermatoscopy, spectrophotometry and high-frequency ultrasound imaging techniques to differentiate malignant lesions from benign moles

Detecting skin cancer via the use of skin biopsies is the bread and butter of many dermatopathology practices. But new technologies that can instantly detect and distinguish different types of skin malignancies may result in a reduced flow of skin biopsies to dermatopathologists in the not-too-distant future.

This may happen because a team of researchers from two universities in Lithuania (Kaunas University of Technology and Lithuanian University of Health Sciences) has developed a patented computer-aided diagnostic (CADx) system capable of differentiating melanoma from a benign nevus [mole] with accuracy greater than 90%, their study of 100 patients showed.

In, “Diagnostics of Melanocytic Skin Tumours by a Combination of Ultrasonic, Dermatoscopic, and Spectrophotometric Image Parameters,” published in Diagnostics, a peer-reviewed, open-access MDPI journal, the scientists noted that their hybrid method combines the three most promising noninvasive quantitative imaging techniques in use for diagnosing melanomas:

The new technique achieved a more accurate method of differentiating melanoma from benign lesions, according to the researchers.

“The novelty of our method is that it combines diagnostic information obtained from different non-invasive imaging technologies such as optical spectrophotometry and [high-frequency] ultrasound. Based on the results of our research, we can confirm that the developed automated system can complement the non-invasive diagnostic methods currently applied in the medical practice by efficiently differentiating melanoma from a melanocytic mole,” said Renaldas Raišutis, PhD, coauthor of the study, in a KTU news release.

Graph of skin cancer rates by state

According to the Skin Cancer Foundation, one in five Americans will develop skin cancer by the age of 70 and more than two people in the United States die of skin cancer every hour. Early diagnosis is vital. If a malignant melanoma—the most lethal type of skin cancer—is found early, the five-year survival rate is 99%. (Graphic copyright: Healthline.)

“An efficient diagnosis of an early-stage malignant skin tumor could save critical time, more patients could be examined, and more of them could be saved,” Raišutis said in the news release. He added that the CADx-based diagnostic system is aimed at medical professionals but at a price that makes it affordable for smaller medical institutions. The Lithuanian team also is working to design a system that could be marketed for home use.

New Non-invasive Optical Technology May Reduce Demand for Skin Biopsies

A systematic review article published in Frontiers in Medicine Dermatology compared current diagnostic techniques for melanoma. It noted, “The current gold standard for melanoma diagnosis is the administration of dermoscopy, followed by a biopsy and subsequent histopathological analysis of the excised tissue. To minimize the risk of misdiagnosis of true melanomas, a significant number of dermoscopically ambiguous lesions are biopsied [increasing] the overall diagnostic costs and time to obtain the final diagnosis.”

But continuing technological innovations may be setting the stage for a reduction in the number of skin biopsies performed each year. In addition to the novel diagnostic method announced by the Lithuanian researchers, an Israeli scientist has created an innovative optical technology that can instantly and non-invasively detect and distinguish between three primary skin cancers:

Abraham Katzir, PhD, a physics professor at Tel Aviv University, has developed a fiber-optic evanescent wave spectroscopy (FEWS) system based on middle infrared transmitting AgCIBr fibers and a Fourier-transform infrared spectrometer that determines the properties of the various skin lesions and identifies them based on their coloration within the infrared spectrum.

Abraham Katzir, PhD and patient

Tel Aviv University Physics Professor Abraham Katzir, PhD (above), demonstrates his new method of detecting cancerous skin lesion, which employs infrared sensors and optical fibers to determine the properties of various lesions on the skin and identify them based on their coloration within the infrared spectrum. (Photo copyright: Tel Aviv University.)

“We figured that with the help of devices that can identify these colors, healthy skin and each of the benign and malignant lesions would have different ‘colors,’ which would enable us to identify melanoma,” Katzir said in an Israel 21c news article.

The Israeli researchers published their study of 100 patients at a major Israeli hospital in Medical Physics, a journal of the American Association of Physicists in Medicine (AAPM).

“Melanoma is a life-threatening cancer, so it is very important to diagnose it early on, when it is still superficial,” Katzir told Israel 21c, adding that the new technology has the potential to cause “dramatic change” in the field of diagnosing and treating skin cancer, “and perhaps other types of cancer as well.”

As advancements in the non-invasive diagnosis of skin cancers continue, dermatopathologists—and in fact all anatomic and histopathology practices—should prepare for the financial impact this change may have on their clinical practices as demand for skin biopsies decreases.

Andrea Downing Peck

Related Information

Novel Method Develop by Lithuanian Scientists Can Reach More than 90% Accuracy in Detecting Melanoma

Diagnostics of Melanocytic Skin Tumours by a Combination of Ultrasonic, Dermatoscopic and Spectrophotometric Image Parameters

Scientist Develops Instant Non-Invasive Cancer Detection Technology

Technical Note: Non-Invasive Mid-IR Fiber-Optic Evanescent Wave Spectroscopy (FEWS) For Early Detection of Skin Cancers

Comparative Analysis of Diagnostic Techniques for Melanoma Detection: A Systematic Review of Diagnostic Test Accuracy Studies and Meta-Analysis

Proof of Concept Study Demonstrates Machine Learning and AI Can Identify Cancer Cells Based on pH Levels; May Have Applications in Surgical Pathology

The new method employs a pH sensitive dye and AI algorithms to ‘distinguish between cells originating from normal and cancerous tissue, as well as among different types of cancer’ the researchers said

Might a pH-sensitive dye in tandem with an image analysis solution soon be used to identify cancerous cells within blood samples as well within tissue? Recent research indicates that could be a possibility. If further studies and clinical trials confirm this capability, then anatomic pathologists could gain another valuable tool to use in diagnosing cancers and other types of disease.

Currently, surgical pathologists use a variety of hematoxylin and eosin stains (H/E) to bring out useful features in cells and cell structures. So, staining tissue on glass slides is a common practice. Now, thanks to machine learning and artificial intelligence, anatomic pathologists may soon have a similar tool for spotting cancer cells within both tissue and blood samples.

Researchers at the National University of Singapore (NUS) have developed a method for identifying cancer that uses a pH sensitive dye called bromothymol blue. The dye reacts to various levels of acidity in cancer cells by turning colors. “The pH inside cancer cells tends to be higher than that of healthy cells. This phenomenon occurs at the very early phases of cancer development and becomes amplified as it progresses,” Labroots reported.

In “Machine Learning Based Approach to pH Imaging and Classification of Single Cancer Cells,” published in the journal APL Bioengineering, the NUS researchers wrote, “Here, we leverage a recently developed pH imaging modality and machine learning-based single-cell segmentation and classification to identify different cancer cell lines based on their characteristic intracellular pH. This simple method opens up the potential to perform rapid noninvasive identification of living cancer cells for early cancer diagnosis and further downstream analyses.”

According to an NUS news release, the bromothymol blue dye is “applied onto patients’ cells” being held ex vivo in cell culture dishes. The dye’s color changes depending on the acidity level of the cancer cells it encounters. Microscopic images of the now-visible cancers cells are taken, and a machine-learning algorithm analyzes the images before generating a report for the anatomic pathologist.

The NUS researchers claim the test can provide answers in about half an hour with 95% accuracy, Labroots reported.

“The ability to analyze single cells is one of the holy grails of health innovation for precision medicine or personalized therapy. Our proof-of-concept study demonstrates the potential of our technique to be used as a fast, inexpensive and accurate tool for cancer diagnosis,” said Lim Chwee Teck, PhD, NUS Society Professor and Director of NUS’ Institute for Health Innovation and Technology, in the NUS news release.

Lim Chwee Teck, PhD

The novel technique for differentiating cancer cells from non-cancerous cells being developed at the National University of Singapore (NUS) could eventually become useful in detecting cancer cells in tissue samples, either obtained from tumor biopsies or blood samples. “As the number of cells in these samples can be in millions or even billions, the ability to detect the very few cancer cells among the others will be useful for clinicians,” NUS Society Professor and Director of NUS’ Institute for Health Innovation and Technology, Lim Chwee Teck, PhD (above) told The Straits Times. (Photo copyright: The Straits Times.)

AI Cell Analysis versus Laborious Medical Laboratory Steps

By developing an AI-driven method, Professor Lim and the NUS team sought to improve upon time-consuming techniques for identifying cells that traditionally involve using florescent probes, nanoparticles, and labeling steps, or for cells to be fixed or terminated.

“Unlike other cell analysis techniques, our approach uses simple, inexpensive equipment, and does not require lengthy preparation and sophisticated devices. Using AI, we are able to screen cells faster and accurately,” Professor Lim told Labroots. “Furthermore, we can monitor and analyze living cells without causing any toxicity to the cells or the need to kill them.”

The new technique may have implications for cancer detection in tumor tissue as well as in liquid biopsies.

“We are also exploring the possibility of performing the real-time analysis on circulating cancer cells suspended in blood,” Professor Lim said in the NUS news release. “One potential application for this would be in liquid biopsy where tumor cells that escaped from a primary tumor can be isolated in a minimally-invasive fashion from bodily fluids such as blood.”

Diagnosing Cancer in Real Time

The NUS’ method requires more research and clinical studies before it could become an actual tool for anatomic pathologists and other cancer diagnosticians. Additionally, the NUS researchers acknowledged that the focus on only four cell lines (normal cells, benign breast tumor cells, breast cancer cells, and pancreatic cancer cells) limited their study, as did lack of comparison with conventional florescent pH indicators.

Still, the NUS scientists are already planning more studies to advance their concept to different stages of cell malignancy. They envision a “real-time” version of the technique to enable recognition of cells and fast separation of those that need to be referred to clinical laboratories for molecular testing and/or genetic sequencing.

Medical laboratory leaders may want to follow the NUS study. An inexpensive AI-driven method that can accurately detect and classify cancer cells based on pH within the cells is provocative and may be eventually become integrated with other cancer diagnostics.

Donna Marie Pocius

Related Information

Machine Learning-Based Approach to pH Imaging and Classification of Single Cancer Cells

Machine Learning Can Identify Cancerous Cells by Their Acidity

NUS Researchers Harness AI to Identify Cancer Cells by Their Acidity: Novel Technique Paves Way for Faster, Inexpensive, and Accurate Cancer Diagnosis

AI Test Distinguishes Cancer Cells from Healthy Ones Based on Acidity Levels

Researchers Use AI to Identify the pH of Cancer Cells

Scientists Identify Growing Number of COVID-19 Variants, But Not All Clinical Laboratories Have the Capability to Test for Variants

Fear that immunity-resistant mutations of SARS-CoV-2 will emerge are real and the scientific community is paying close attention

Detection of an increasing number of new variants of the SARS-CoV-2 coronavirus raises the possibility that a new strain of COVID-19 might emerge that brings new problems to the management of the pandemic. Public health officials and clinical laboratory scientists are on the alert to determine if any new COVID-19 variant is more virulent or more easily transmissible.

Pathologists, along with the rest of the scientific community worldwide, are following reports of increasing coronavirus mutations with growing concern. The Alpha variant (Lineage B.1.1.7) accounted for most of the COVID-19 cases in April of 2021 in the US, though it was first identified in the United Kingdom. That was followed by the Iota variant (Lineage B.1.526) first identified in New York City. A series of other variants were to follow. Scientists were not surprised. It is normal for viruses to mutate, so they logged and tracked the mutations.

Then, the Delta variant (Lineage B.1.617.2) emerged during a severe outbreak in India. At first, it did not seem more threatening than any other variant, but that changed very quickly. Delta was different.

“The speed with which it dominated the pandemic has left scientists nervous about what the virus will do next. The variant battles of 2021 are part of a longer war, one that is far from over,” The Washington Post reported, which added, “Today, [Delta] has nearly wiped out all of its rivals. The coronavirus pandemic in America has become a Delta pandemic. By the end of July, it accounted for 93.4% of new infections, according to the Centers for Disease Control and Prevention.”

Why is Delta the Worst COVID-19 Variant So Far?

The Delta variant has two advantages that scientists know about:

  • Stickier spike protein than the spike on the original SARS-CoV-2 coronavirus, as well as on the other, earlier variants. This means that the Delta variant stands a better chance of remaining in a person’s nose or throat long enough to reproduce.
  • Faster replication. When a virus mutation has more opportunity to reproduce, it quickly becomes the main viral strain. This is the case with the Delta variant. Experts say that the viral load in patients with Delta is around 1,000 times higher than in patients with the original virus.
Colorized scanning electron micrograph of an apoptotic cell that is infected with the SARS-COV-2 virus

The image above is a “Colorized scanning electron micrograph of an apoptotic cell (tan) heavily infected with SARS-COV-2 virus particles (orange), isolated from a patient sample,” Newsweek reported. (Photo copyright: National Institute of Allergy and Infectious Diseases/Newsweek.)

Will More Dangerous SARS-CoV-2 Variants Appear?

“The great fear is that nature could spit out some new variant that completely saps the power of vaccines and upends the progress we’ve made against the pandemic. But to virologists and immunologists, such a possibility seems very unlikely,” STAT reported.

That is because, unlike Influenza, which is also a coronavirus, SARS-CoV-2 variants are not able to share genetic materials and recombine into deadlier variants. Thus, scientists are skeptical that a variant could appear and wipe out the progress made with vaccines and treatments.

One of the reasons the Flu vaccine changes every year is Influenza’s ability to recombine into variants that can evade immunity. Therefore, scientists are beginning to suspect that SARS-CoV-2, like the Flu, will likely be around for a while.

“I don’t think eradication is on the table. But I think we could come up with something that’s better than what we have for the flu,” Sharone Green, MD, Associate Professor of Medicine, Division of Infectious Diseases and Immunology and Infection Control Officer at University of Massachusetts Medical School, told Newsweek.

Limiting Infections and Replication

Several factors combined to create the COVID-19 pandemic. But SARS-CoV-2 was a novel coronavirus, meaning it was a new pathogen of a known virus. This meant every person on the planet was a potential host.

The situation now is different. Thanks to natural immunity, vaccines, and treatments that shorten the infection, the SARS-CoV-2 coronavirus has less chance to replicate.

“The pressure is there, but the opportunity is not. The virus has to replicate in order to mutate, but each virus doesn’t get many lottery tickets in a vaccinated person who’s infected,” Jeremy Kamil, PhD, Associate Professor of Microbiology and Immunology at LSU Health in Shreveport, La., told STAT.

Tracking Variants of Interest and Variants of Concern

The World Health Organization (WHO) has been monitoring the viral evolution of SARS-CoV-2 since the beginning of the pandemic. In late 2020, the WHO created categories for tracking variants:

The WHO’s lists of VOIs and VOCs help inform the global response to the COVID-19 pandemic.

According to the CDC’s SARS-CoV-2 Variant Classifications and Definitions:

VOIs are “A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.”

Current VOIs include:

  • Eta (Lineage B.1.525), detected in multiple countries, designated a VOI in March 2021.
  • Iota (Lineage B.1.526), US, first detected in November 2020, designated a VOI in March 2021.
  • Kappa (lineage B.1.617.1), India, first detected in October 2020, designated a VOI in April 2021.
  • Lambda (lineage C.37), Peru, first detected in December 2020, designated a VOI in June 2021.

VOCs, on the other hand, demonstrate all the characteristics of VOIs and also demonstrate “an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.”

Current VOCs include:

  • Alpha (lineage B.1.1.7), first detected in the UK, September 2020.
  • Beta (lineage B.1.351), first detected in South Africa, May 2020.
  • Gamma (lineage P.1), first detected in Brazil, November 2020.
  • Delta (lineage B.1.617.2), first detected in India, October 2020.

Will Vaccines Stop Working?

With each new variant, there tends to be a flurry of media attention and fearmongering. That a variant could emerge which would render our current vaccines ineffective has the scientific community’s attention.

“There is intense interest in whether mutations in the spike glycoprotein mediate escape from host antibodies and could potentially compromise vaccine effectiveness, since spike is the major viral antigen in the current vaccines,” wrote Adam S. Lauring, MD, PhD, and Emma B. Hodcroft, PhD, in “Genetic Variants of SARS-CoV-2­—What Do They Mean?” published in the Journal of the American Medical Association (JAMA). 

“Because current vaccines provoke an immune response to the entire spike protein, it is hoped that effective protection may still occur despite a few changes at antigenic sites in SARS-CoV-2 variants,” they added.

Future events may justify the optimism that the ongoing effectiveness of vaccines will help with many COVID-19 variants. But pathologists and clinical laboratory leaders may want to be vigilant, because as infection rates increase, so do workloads and demands on critical resources in their medical laboratories.

Dava Stewart

Related Information

‘Goldilocks Virus’: Delta Vanquishes All Variant Rivals as Scientists Race to Understand Its Tricks

Viral Evolution 101: Why the Coronavirus Has Changed as It Has, and What It Means Going Forward

A Doomsday COVID Variant Worse than Delta and Lambda May Be Coming, Scientists Say

Tracking SARS-CoV-2 Variants

Genetic Variants of SARS-CoV-2—What Do They Mean?

Dey Laboratory Research Finds Bile Acids Affect Gut Motility and the Human Microbiome, Insights That May Lead to New Clinical Laboratory Tests

These new findings may affect how microbiology labs and physicians diagnose and treat several gastrointestinal conditions

Once again, a research effort has teased out new insights into the role the human microbiome plays in our digestive processes. Microbiologist and medical laboratory managers will be interested to learn that, according to the study team, specific microbes have a role in regulating how fast food moves through the digestive tract.

Researchers at the Dey Laboratory in Seattle recently examined the function of microbial bile acid metabolism in gut motility. They determined that “metabolites generated by the gut microbiome regulate gut transit,” according to a new paper published by the Fred Hutchinson Cancer Research Center (Fred Hutch).

“These findings have potential implications for the treatment of gastrointestinal conditions,” noted a Fred Hutch news release. This may mean new clinical laboratory tests to identify these strains of bacteria, along with new therapies for treating patients.

Gut motility (aka, Peristalsis) is the term used to describe the movement of food from the time it enters via the mouth until it leaves the body. This movement, the researchers found, is regulated by interactions between diet, the enteric nervous system (ENS) and the gut microbiota via processes that include bile acid metabolism.

Sex, Diet, and Lifestyle All Affect Treatment for Gastrointestinal Diseases

The Dey Laboratory researchers also discovered that sex was a significant variable in determining transit times with males having larger pro-motility effects.

In “Microbiome-encoded Bile Acid Metabolism Modulates Colonic Transit Times,” the Dey Laboratory researchers noted that previous studies have shown higher motility and varying bile acid profiles between men and women. They published their study in iScience, an open-access Cell Press journal.

“Our results suggest that strategies for treating or preventing gastrointestinal diseases may need to be tailored to sex and to biogeography of the gut,” they wrote. “While targeting the microbiome and the ENS is justified, our observation of significant transcriptional responses to defined interventions in a highly controlled gnotobiotic setting also highlights challenges to clinical translation.”

The researchers concluded that:

  • Gut microbiome-generated bile acids regulate colonic transit via TGR5 protein.
  • Lithocholic acid (LCA) had the largest colonic pro-motility effect.
  • Bile acids exert sex-biased effects on gut transit times.
  • Enteric nervous system (ENS) transcriptional responses are regional- and microbiome-specific.

“The human experience—which reflects the aggregate effects of the innumerable dietary ingredients that we consume daily, the hugely diverse metabolically dynamic microbes that inhabit our guts, our own digestive processes, and the interactions of all of the above that result in thousands of gut metabolites—entails significantly more complex and variable transcriptional responses to environmental cues,” the Dey Laboratory scientists concluded.

Dey Lab graphic

To perform their research, the scientists developed both high and low BSH (bile salt hydrolase) bacterial communities for germ-free mice, which are known to exhibit slower gut motility and less complex bile acid profiles than colonized animals. (See graphic above taken from the Dey Laboratory published paper.)

The spice turmeric and dyes were added to the diets of the mice to track gut motility. The mice that were given the BSH-high microbiota had higher fecal concentrations of unconjugated bile acids than those given the BSH-low form of the microbiota. The mice given the BSH-high version also experienced faster transit times, according to the researchers’ iScience paper.

The researchers also concluded that the BSH-high group had greater fecal concentrations of lithocholic acid (LCA) which indicates variations in bile acid metabolism might affect gut transit.

When the scientists infused bile acids directly into mouse colons, variable acids reacted differently with LCA having the fastest transit times. The researchers hypothesized that LCA might signal through a bile receptor known as TGR5 which blocked the effects of LCA on colonic transit times. TGR5, also called G protein-coupled bile acid receptor, functions as a cell surface receptor for bile acids.

The Dey Laboratory team developed a method to measure expression changes in ENS genes and found that neither BSH activity nor gut transit phenotypes were major drivers of gene expression changes. They found that the location of the gut segment, or biogeography, was the leading contributor to ENS signature variance between samples.

Neelendu Dey, MD

“We expected to see shared host transcriptional responses in mice harboring communities with similar metabolic profiles. However, we did not see this for the most part,” explained gastroenterologist Neelendu Dey, MD (above), a physician/scientist and Assistant Professor, Clinical Research Division, at Fred Hutchinson Cancer Research Center, in the press release. “If anything, shared responses were regional, and these signatures did not cluster by BSH/motility phenotypes.” (Photo copyright: Seattle Cancer Care Alliance.)

The scientists “identified consortium-specific transcriptional changes in genes involved in ENS signaling, development, maintenance, and bile acid metabolism, and these differed across regions of the GI tract. Together these findings indicate that ENS transcriptional responses are regional and microbiome-specific,” according to the Fred Hutch press release.

“This remains a confusing part of the story for us—how is it that we can see predictable host motility responses when colonizing the guts of gnotobiotic mice with phenotypically defined communities, but the middle-man (the host enteric nervous system) appears to have such varied responses?” the Dey Laboratory researchers noted in the press release.

“It suggests that gut motility phenotypes that appear similar may in fact represent (when we look under the hood) diverse host physiologic phenotypes that we are just beginning to understand,” they added.

The results of this study could have potential implications for the precision medicine diagnosis and treatment of gastrointestinal illnesses.

Blue Poop Challenge

Earlier this year, people were encouraged to participate in the “blue poop challenge” conducted by research company ZOE Global Limited (ZOE) to determine how long it takes food to travel through the body.

ZOE is also known for collaborating with King’s College London, and Guy’s and St Thomas’ Hospitals to create the COVID Symptom Tracker mobile app (now known as the COVID Symptom Study).

For the Blue Poop Challenge, individuals are asked to eat blue muffins and then report on the company’s website as to how long it took for the blue dye to appear in their stools.

The purpose of this ongoing study is to reveal pertinent information about an individual’s gut health and microbiome.

Since 2010, Dark Daily has reported on dozens of research studies and innovative developments involving human microbiome and gut bacteria and their critical importance in the development of clinical laboratory testing, drug therapies, and precision medicine.

In “University of Utah and Sloan Kettering Institute Study Sheds Light on How the Body Recognizes ‘Good’ from Bad Bacteria in the Microbiome,” we reported on research being conducted at the University of Utah and the Sloan Kettering Institute (SKI) which found that early in life intestinal microorganisms “educate” the thymus to develop T cells.

These studies’ findings could lead to improved immune system therapeutics and associated clinical laboratory tests.

“All of this suggests the potential in the future for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.

More research is needed in these areas. But gut bacteria and the human microbiome are an integral part of our health and wellbeing. It is worth keeping an eye on new developments in those fields of study.

JP Schlingman

Related Information

Keeping Regular: Gut Bacteria Modulate Transit Time via Bile Acids

Microbiome-encoded Bile Acid Metabolism Modulates Colonic Transit Times

Does the Viral Blue Poop Challenge Really Tell You Anything about Gut Health?

The Blue Poop Challenge Could Tell You Important Info about Your Gut Health—Here’s How It Works

University of Utah and Sloan Kettering Institute Study Sheds Light on How the Body Recognizes ‘Good’ from Bad Bacteria in the Microbiome

Forbes Ranks Epic’s Judith Faulkner the Richest Woman in Healthcare in Its 2021 List of 100 Richest Self-Made Women in US

Within the in vitro diagnostics and clinical laboratory space, Bio-Rad’s Alice Schwartz and 23andMe’s Anne Wojcicki also were recognized by Forbes

At $6.5 billion net worth, Forbes, in its 2021 list of the 100 richest self-made women in the US, ranked Judith Faulkner, Chief Executive Officer and founder of Epic Systems Corp., in second place overall. But in the industry of healthcare, she tops the list by far. The next nearest healthcare-related “richest woman” is Alice Schwartz, co-founder of Bio-Rad Laboratories, at $2.9 billion.

Faulkner was surpassed on Forbes’ list only by roofing material magnate Diane Hendricks, co-founder of ABC Supply Co., whose net worth of $11 billion puts her squarely in the top spot.

Richest Self-Made Women in Healthcare

Becker’s Hospital Review highlighted the seven richest “self-made” women who ran healthcare-related companies. They include:

Also listed by Forbes was Anne Wojcicki, CEO and founder of 23andMe, a personal genomics and biotechnology company. Wojcicki’s net worth of $1.1 billion puts her in the 25th position, according to Forbes.

In “Genetic Test Company 23andMe Completes Merger with Richard Branson’s VG Acquisition Corp., Stock Now Trades on NASDAQ,” Dark Daily noted that since the Sunnyvale, Calif. direct-to-consumer (DTC) genetic testing company will now be filing quarterly earnings reports, pathologists and clinical laboratory managers will have the opportunity to learn more about how 23andMe serves the consumer market for genetic types and how it is generating revenue from its huge database containing the genetic sequences from millions of people.

Judith Faulkner and Alice Schwartz

Judith Faulkner (left), founder and CEO of Epic Systems Corp., and Alice Schwartz (right), co-founder of Bio-Rad Laboratories, ranked 2nd and 10th respectively in Forbes’ list of the top 100 richest self-made women. In healthcare, Faulkner ranks 1st and Schwartz 2nd. Clinical laboratory personnel will likely be familiar with Epic Beaker, which, according to Healthcare IT Leaders, “is Epic’s laboratory information system (LIS) for hospitals, clinics, patient service centers, and reference labs. The software supports common workflows for clinical pathology (CP) labs as well as anatomic pathology (AP) labs.”  (Photo copyrights: HIT Consultant/Science History Institute.)

How did Faulkner Make Epic So Epic?

It all started in 1979 when Faulkner and a colleague invested $70,000 to launch Human Services Computing, which became Epic, noted Forbes in “The Billionaire Who Controls Your Medical Records.”

“I always liked making things out of clay. And the computer was clay of the mind. Instead of physical, it was mental,” Faulkner, who is 77, told Forbes.

Company milestones noted by Forbes include:

  • Inking a deal in 2004 with Kaiser Permanente for a three-year, $400-million project.
  • Moving in 2005 to a corporate campus in southern Wisconsin—an “adult Disney World” with the largest underground auditoriums and more “fantastical” buildings.
  • More recently, AdventHealth of Altamonte Springs, Fla., contracted with Epic for a $650 million remote build and installation.

“Epic’s system has tentacles that go out through amazing networks. You can actually help a person get the care they need wherever they need to get it,” AdventHealth’s CEO Terry Shaw told Forbes.

In about two years, Epic plans to launch an artificial intelligence (AI) Electronic Health Record (EHR) documentation tool aimed at transcribing clinician and patient conversations in real-time, EHR Intelligence reported.

However, Epic may face competition from IT startups in areas including ancillary services, where clinical laboratories, for example, are seeking genomic data storage and introducing new genetic tests, according to Becker’s Hospital Review in its report on analysis by CB Insights, titled, “Unbundling Epic: How The Electronic Health Record Market Is Being Disrupted.”

“I think that what will happen is that a few of them will do very well. And the majority of them won’t. “It’s not us as much as the health systems who have to respond to the patient saying, ‘Send my data here,’ or ‘Send my data there,’” Faulkner told Forbes.

Bio-Rad’s Alice Schwartz an IVD ‘Pioneer’

As Faulkner rose to prominence in healthcare IT, Alice Schwartz of Bio-Rad Laboratories found massive success in the in vitro diagnostics industry.

She and her late husband, David, started Bio-Rad with $720 in 1952 in Berkeley, Calif. They were intent on offering life science products and services aimed at identifying, separating, purifying, and analyzing chemical and biological materials, notes the company’s website.

“They were at the right place and at the right time as they became pioneers in the industry,” International Business Times (IBT) stated.

Bio-Rad Laboratories (NYSE:BIO and BIOb) of Hercules, Calif., offers life science research and clinical diagnostic products. The company’s second quarter (Q2) 2021 net sales were $715.9 million, an increase of about 33% compared to $536.9 million in Q2 2020, according to a news release. Its Clinical Diagnostics segment Q2 sales were $380 million, an increase of 34% compared to 2020.

Norman Schwartz, the founders’ son, is Bio-Rad’s Chairman of the Board,

President, and CEO. However, at age 94, Alice Schwartz, the oldest person on Forbes’ richest self-made women list, “has no sign of stopping soon,” IBT reported.

Lists are fun. Medical laboratory and diagnostics professionals may admire such foresight and perseverance. Judith Faulkner and Alice Schwartz are extraordinary examples of innovative thinkers in healthcare. There are others­—many in clinical laboratories and pathology groups.

Donna Marie Pocius

Related Information

Forbes’ Ranking of the Country’s Most Successful Women Entrepreneurs and Executives 2021

Healthcare’s Richest Self-Made Women, Per Forbes

Epic Systems Founder-CEO Judy Faulkner Wields Great Power and Responsibility in Healthcare IT

Unbundling Epic: How the Electronic Health Record Market is Being Disrupted

The Billionaire Who Controls Your Medical Records

Epic in Process of Developing AI EHR Documentation Assistant

Epic’s Revenue Hit $3.3B in 2020; 10 ways the EHR Giant’s Dominance is Opening Doors for Competition

Bio-Rad Reports Second Quarter 2021 Financial Results

Alice Schwartz Net Worth: Oldest, Richest Woman in U.S. is Worth $2.2B

Genetic Test Company 23andMe Completes Merger with Richard Branson’s VG Acquisition Corp; Stock Now Trades on NASDAQ

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