New technique could allow emergency responders to determine severity of LVO stroke while patient is still in the ambulance
Researchers at Brigham and Women’s Hospital in Massachusetts say they have developed a clinical laboratory test that can quickly determine whether a patient is experiencing one of the deadliest types of strokes, known as an ischemiclarge vessel occlusion (LVO) stroke. The development team believes this new assay could be deployed as a point-of-care test to enable faster diagnosis of stroke events.
The test combines measurement of two blood plasma biomarkers with an established clinical score used by clinicians and EMS personnel to assess stroke severity. Compared with current approaches, their technique more accurately differentiates LVO strokes from other types of strokes, making it more likely that patients receive appropriate treatment in a timely manner, the researchers said in a Brigham news release.
Dark Daily has long predicted that advances in technology and computing power would make it possible for pathologists and clinical laboratory scientists to combine multiple established biomarkers (individually not associated with the disease state targeted) with other clinical and patient data to create the ability to make an accurate and earlier diagnosis.
Ultimately, Brigham’s research could “aid in the development of a point‐of‐care diagnostic test capable of guiding prehospital LVO stroke triage,” wrote Joshua Bernstock, MD, PhD, Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital, lead author of the study, and colleagues.
“We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care,” said Joshua Bernstock, MD, PhD (above), Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital and lead author of the Brigham study that developed the clinical laboratory test that the researchers say can enable emergency caregivers to determine quickly and accurately if a patient is having an ischemic large vessel occlusion (LVO) stroke. (Photo copyright: Brigham and Women’s Hospital.)
Early Identification of LVO Stroke
As explained in the news release, an LVO stroke is a type of ischemic stroke caused by obstruction in a major brain artery. The researchers noted that LVO strokes account for “62% of poststroke disabilities and 96% of poststroke death.”
These strokes are readily treatable using endovascular thrombectomy (EVT), in which the blockages are surgically removed, the news release note. However, the researchers observed that EVT “requires specialized teams and equipment, limiting its availability to comprehensive stroke centers and other EVT‐capable centers.”
This can lead to delays as patients are transferred to those facilities, worsening outcomes and increasing the risk of death, the researchers wrote in Stroke: Vascular and Interventional Neurology. So, early identification of LVO stroke is key to ensuring patients receive timely treatment.
Identifying False Negatives/Positives
One challenge, the news release notes, is that brain bleeds (hemorrhagic stroke) can present similar symptoms, yet require “vastly different” treatment.
“A growing body of work has, therefore, evaluated prehospital stroke assessment scales in an effort to identify LVO strokes in the field,” the researchers wrote. “However, such severity scales lack the sensitivity and specificity required for triaging LVO patients with confidence, resulting in false negatives in patients with LVO as well as false positives in patients with stroke mimics or hemorrhagic stroke.”
As explained by EMS Aware, these assessment scales, such as FAST-ED (field assessment stroke triage for emergency destination) and RACE (rapid arterial occlusion evaluation), attempt to determine the severity of a stroke by assigning scores based on symptoms such as facial palsy, arm weakness, and speech difficulties.
To develop their test, Bernstock and colleagues proposed combining the scales with measurement of two blood proteins:
In their study, they attempted to validate cutoff values for the biomarkers and scales.
To do so, the researchers analyzed data from 323 patients admitted to a Florida hospital with suspected stroke between May 2021 and August 2022. Each was assigned to one of four diagnostic categories based on clinical data from their medical records, which included results of computed tomography (CT scan) or magnetic resonance angiography (MRA). The diagnostic categories included:
The patients were assessed using five stroke severity scales. The researchers used frozen blood samples from the patients to measure the biomarkers. They then used this data to determine the likelihood of LVO stroke and compared the results with the diagnoses as determined by the clinical data.
“Combinations of the blood biomarkers with the scales FAST‐ED or RACE showed the best performance for LVO detection, with a specificity of 94% (for either scale combination) and a sensitivity of 71% for both scales,” the researchers wrote.
Sensitivity was higher in patients who presented within the first six hours from onset of symptoms.
“Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage,” the researchers wrote. However, they also suggested that their algorithm could be adjusted to enable early identification of hemorrhagic stroke.
The researchers noted that they chose biomarker cutoffs to maximize specificity, so “a certain number of LVOs are missed. However, as such patients default into ‘standard‐of‐care’ triaging pathways, such a decision is unlikely to represent much clinical risk.”
Testing in the Field
The Brigham researchers used established biological biomarkers combined with modern computing—in combination with the scores from a field assessment test—to develop their new clinical laboratory test that identifies the type of stroke.
Their next step is to carry out “another prospective trial to measure the test’s performance when used in an ambulance,” the news release states. “They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.”
“In stroke care, time is brain,” Bernstock said. “The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative.”
More research and clinical studies are needed. However, the fact that the Brigham team wants to deploy this approach in ambulances is an indication that there is high clinical value from this approach.
Clinical pathologists and medical laboratory managers will want to watch the ongoing development and deployment of this new assay, whether it is run in near-patient settings or core clinical laboratories in support of patients presenting in emergency departments.
Should further study validate these findings, clinical laboratories managing hospital blood banks would be among the first to benefit from an abundance of universal donor blood
In a surprising outcome for microbiome research, scientists at the Technical University of Denmark (DTU) and Sweden’s Lund University discovered that the bacteria Akkermansia muciniphila, which resides in the human gut, produces enzymes that can be used to process whole blood in ways that could help produce type-O blood. This “universal” blood type can be given to patients during transfusions when other blood types are in short supply.
Receiving the wrong type of blood via a transfusion could result in a fatal reaction where the immune system launches an attack on foreign antigens. As blood bankers and clinical laboratory scientists know, the A antigens in type A blood are not compatible with the B antigens in type B blood. Type-O blood completely lacks these antigens, which explains why it can be used for individuals of any blood type.
The DTU/Lund discovery—still in its initial stages of development—could eventually give blood bankers in hospital laboratories a way to expand their supply of universal type-O blood. Although individuals with type-O blood are universal donors, often the available supply is inadequate to meet the demand.
“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognized as problematic for transfusion safety,” said Maher Abou Hachem, PhD, Professor of Biotechnology and Biomedicine at DTU, one of the authors of the study, in a news release.
Discovering a way that ensures any blood type can donate blood for all blood types could increase the supply of donor blood while reducing the costs and logistics affiliated with storing four separate blood types. Additionally, the production of a universal blood type using gut microorganisms could reduce the waste associated with blood products nearing their expiration dates.
“We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood,” said Maher Abou Hachem, PhD (above), Professor of Biotechnology and Biomedicine at DTU in a news release. “Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” he added. Hospital clinical laboratories that manage blood banks will be among the first to benefit from this new process once it is developed and cleared for use in patient care. (Photo copyright: Technical University of Denmark.)
Creating Universal Donor Blood
The bacterium Akkermansia muciniphila is abundant in the guts of healthy humans. It produces valuable compounds, and it is able to break down mucus in the gut and can have significant, positive effects on body weight and metabolic markers.
“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group ABO antigens. This hypothesis turned out to be correct,” Hachem noted in the DTU news release.
“Instead of doing the work ourselves and synthesizing artificial enzymes, we’ve asked the question: What looks like a red [blood] cell surface? The mucus in our gut does. So, we simply borrowed the enzymes from the bacteria that normally metabolize mucus and then applied them to the red [blood] cells,” Martin Olsson MD, PhD, professor of hematology and transfusion medicine at Lund University, told Live Science. “If you think about it, it’s quite beautiful.”
The researchers successfully identified long strings of sugar structures known as antigens that render one blood type incompatible with another. These antigens define the four blood types: A, B, AB and O. They then used a solution of gut bacteria enzymes to remove the sugar molecules present on the surface of red blood cells (RBCs).
“We biochemically evaluated 23 Akkermansiaglycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions,” the study authors wrote in Nature Microbiology. “Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analysis of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module.”
“Universal blood will create a more efficient utilization of donor blood, and also avoid giving ABO-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create ABO-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste,” Olsson said in the news release.
Future Progress
The researchers have applied for a patent for the enzymes and their method of enzyme treatment. The two educational institutions hope to make further progress on this joint project over the next three years. They eventually hope to test their theory in controlled patient trials and make it available for commercial production and clinical use.
More research and clinical studies are needed to prove the effectiveness of this discovery. Clinical laboratory professionals—particularly those who manage hospital blood banks—will want to follow DTU’s research. It could someday lead to the availability of a more abundant supply of universal donor blood for transfusions.
Study found highest incidences of occupational carcinogenesis among clinical laboratory and histology technicians, followed by pathologists
It has been known for years that formalin (a form of formaldehyde used as a disinfectant and preservative in the handling of tissues samples in anatomy, pathology, and microbiology labs), as well as xylene and toluene, are dangerous to clinical laboratory workers. Nations around the world have taken steps to minimize exposure to these dangerous chemicals. However, a recent study in Iran found that those measures may not have gone far enough to protect histology and clinical laboratory technicians, pathologists, and medical laboratory scientists.
The study conducted by researchers in the Department of Occupational Health Engineering, School of Public Health, at Tehran University of Medical Sciences, showed that levels of exposure to these chemicals is still significantly higher than recommended, resulting in a higher risk for cancer among lab workers in Iran’s hospitals.
“Employing risk assessment techniques as a complementary tool in monitoring programs for respiratory exposure in the different work setting should be considered to protect the staffs against both non-cancerous and cancer-related hazards,” the study authors wrote.
Lessons learned from the Iranian hospital lab study could benefit clinical laboratory workers in US hospitals and help those who work with formaldehyde, toluene, and xylene worldwide to reduce their chances of developing a vascular condition known as Raynaud’s phenomenon (shown above) which can lead to necrosis and gangrene, as well as other dangerous health conditions affecting the lungs, brain, and other systems and organs in the body. (Photo copyright: Wikipedia.)
Study Details
The Iranian study considered the carcinogenic and non-carcinogenic impact of occupational exposure to formaldehyde in the pathology laboratories of four Tehran hospitals. The researchers “used a quantitative risk assessment method proposed by the United States Environmental Protection Agency (EPA), along with its provided database known as the Integrated Risk Information System (IRIS). Respiratory symptoms were assessed using the American Thoracic Society (ATS) questionnaire,” the study authors wrote in NatureScientific Reports.
The scientists found that “91.23% of exposure levels in occupational groups exceed the NIOSH [National Institute for Occupational Safety and Health] standard of 0.016 ppm.” They determined that “41.03% of all the studied subjects were in the definite carcinogenic risk range (LCR > 10−4), 23.08% were in the possible carcinogenic risk range (10−5 < LCR < 10−4), and 35.90% were in the negligible risk range (LCR < 10−6),” they wrote.
“The highest index of occupational carcinogenesis was observed in the group of lab technicians with a risk number of 3.7 × 10-4, followed by pathologists with a risk number of 1.7 × 10-4,” the scientists wrote. “Furthermore, 23.08% of the studied subjects were within the permitted health risk range (HQ < 1.0), while 76.92% were within the unhealthy risk range (HQ > 1.0),” they added.
“Formaldehyde exhibits high solubility in water and is rapidly absorbed by the nasal cavity, sinuses, throat, and mucous membrane of the upper respiratory tract upon exposure,” the study authors wrote. “Consequently, due to the elevated potential for both carcinogenic and non-carcinogenic formaldehyde exposure among pathology staff—particularly laboratory technicians—the implementation of management measures … becomes imperative to lower the exposure levels of all employees below permissible limits.”
Those management measures include:
“Strict guideline adherence and safe work protocols,
“Increasing staff numbers to decrease exposure duration,
“Adoption of engineering solutions such as localized ventilation systems, and
“Use of respiratory protective equipment during sample handling and tissue processing.”
Previous Reports on Exposure Risk to Clinical Lab Workers
The knowledge of the danger behind these chemicals isn’t new.
In 2017, a pathology lab in Auckland, New Zealand, lost its accreditation because formaldehyde levels were so high the lab had to be evacuated nearly every day, The New Zealand Herald reported.
“In epidemiological studies on industrial workers, pathologists and anatomists, the relationship between exposure to formaldehyde and an increased risk of various types of cancer including nasal cavity, nasopharynx, lung, brain, pancreas, prostate, colon and atopic lymphoma system has been determined,” the Iranian scientists wrote in Nature Scientific Reports.
Call for Stronger Regulations
“The Food and Drug Administration (FDA), the Consumer Product Safety Commission (CPSC), and the Environmental Protection Agency have expressed serious concern about the carcinogenicity of formaldehyde,” the Iranian scientists noted, adding that “the potential carcinogenic risk to humans has been studied in a number of cohort and case-control studies.”
There is room for more studies looking at the health effects of exposure to these chemicals among lab workers, as well as continued evaluation of the risks and preventative measures that could be taken. Perhaps tightened regulations will make its way to US labs, echoing more stringent ones of the European Union.
“It is imperative to implement control measures across various hospital departments to mitigate occupational formaldehyde exposure levels proactively. These findings can be valuable for policymakers in the health sector, aiding in the elimination or reduction of airborne formaldehyde exposure in work environments,” the Iranian scientists wrote.
Managers of histology and clinical laboratories may find useful advice in hospital laboratory studies like that coming out of Iran. Protecting the health of lab workers worldwide starts with reducing their exposure to deadly chemicals.
Trend will likely lead to physicians ordering more clinical laboratory screening tests for cancer among all age groups, including young patients
Upticks in colorectal cancer cases among younger populations, as reported in recent news stores, is an issue that has implications for clinical laboratories. According to a study conducted at the University of Missouri-Kansas City (UMKC), the number of colorectal cancer cases in the US has increased greatly since 1999 with the “most dramatic jumps” seen in children, teens, and young adults, a Digestive Disease Week (DDW) news release reported.
“Colorectal cancer is no longer considered just a disease of the elderly population,” said lead researcher Islam Mohamed, MD, an internal medicine resident physician at UMKC. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
The researchers noted in the DDW news release that “colorectal cancer cases, over about two decades, increased by 500% among children, ages 10 to 14; 333% in teens, ages 15 to 19; and 185% among young adults, ages 20 to 24.”
“[The results of the UMKC study] means that there is a trend. We don’t know what to make of it yet. It could be lifestyle factors or genetics, but there is a trend,” lead researcher Islam Mohamed, MD (above), Internal Medicine Resident, University of Missouri-Kansas City, told NBC News. If proved, this trend could lead to increased demand for clinical laboratory screening tests for colorectal and other cancers among young people. (Photo copyright: Digestive Disease Week.)
0.6/100,000 children ages 10 to 14 (a 500% increase).
1.3/100,000 teens ages 15 to 19 (a 333% increase).
Two/100,000 young adults ages 20 to 24 (a 185% increase).
Albeit small numbers, the cases are growing at a rate that is troublesome, according to experts. As NBC put it, “any increase can take on a larger significance” when rates begin at low points.
The study also found incidence of colorectal cancer up in people in their 30s and 40s, reaching by 2020:
6.5/100,000 people ages 30 to 34 (a 71% increase).
11.7/100,000 people ages 35 to 39 (a 58% increase).
20/100,000 people ages 40 to 44 (a 37% increase).
Screening Guidelines May Need to Change
Further research based on UMKC’s study findings could lead to changes in cancer screening guidelines.
“We were screening people from the age of 60 for colon cancer. This has now been lowered to 55, and that is due to be lowered again to 50 over the next few months,” Jude Tidbury, RN, nurse endoscopist and clinical nurse specialist, gastroenterology and endoscopy, at the UK’s East Sussex Healthcare NHS Trust, told Healthline.
In the US, the American Cancer Society advises people of average risk for cancer to start screening for colorectal cancer at age 45. The test options ACS recommends annually include:
What is behind early-onset colorectal cancer among certain age groups? An international study led by Fred Hutchinson Cancer Center (Fred Hutch), Seattle, found “strong correlations” with consuming alcohol and being obese with early-onset colorectal cancer in adults under age 50, according to a news release.
The researchers set out to explore the common genetic variants and causal modifiable risk factors that are behind early-onset colorectal cancer, according to a paper they published in the journal Annals of Oncology.
To do so they used big databases, pulling out 6,176 early-onset colorectal cancer cases and 65,829 controls from sources including:
They focused on “lifestyle factors increasing risk” by comparing the genetic variations in those with colorectal cancer to healthy people, the Fred Hutch news release explained.
“It’s important to see that alcohol and obesity are linked to early-onset colorectal cancer. Also, insulin signaling and infection-related biological pathways. These are all really important to understand—it’s helping us to develop interventions,” said Ulrike Peters, PhD, Professor and Associate Director, Public Health Services Division, Fred Hutch, who co-led the research, in the news release.
Peters noted future research may aim to address data gaps relating to racial and ethnic groups.
More Colorectal Cancer Tests
As studies continue to explore the notion that cancer may not be a disease of aging,
clinical laboratories could see more primary care physicians and healthcare consumers using colorectal cancer screening tests, which require analysis and reporting by labs.
Medical laboratory leaders may want to proactively encourage lab sales and service representatives to educate physician office staff about using the lab’s available resources for screening young adults for colorectal cancer.
Clinical laboratories with mobile phlebotomy programs are positioned to benefit as demand for at-home blood draws increases
Hospital-at-Home (HaH) models of remote healthcare continue to pick up speed. The latest example comes from the 793-bed Mass General Brigham (MGB) health system which partnered with Best Buy Health to build the largest HaH program in the nation, according to Becker’s Hospital Review. This means clinical laboratories will have new opportunities to provide mobile phlebotomy home-draw services for MGB’s HaH patients.
“The health system now has a capacity for acute hospital care at home of 70 patients and is currently treating about 50 to 60 a day. The goal is to move to 10% of Mass General Brigham’s overall capacity, or about 200 to 300 patients,” Becker’s reported.
Best Buy Health provides MGB’s Home Hospital patients with computer tablets and Internet access, Becker’s noted.
“Healthcare is fragmented, the technology doesn’t always connect. Technology is our expertise,” said Chemu Lang’at, COO, Best Buy Health, during the WMIF presentation.
The hospital is the most expensive site of care in the US healthcare industry. Thus, preventing patients from needing to be hospitalized—or treating them in their homes—could reduce the cost of care considerably for both patients and multihospital systems.
“It’s been estimated that 30% of inpatient care will move to the home in the next five years, representing $82 billion in revenue. This is a tremendous opportunity,” said Heather O’Sullivan, MS, RN, A-GNP, Mass General Brigham’s President of Healthcare at Home, during MGB’s presentation at the World Medical Innovation Forum in September, according to Becker’s Hospital Review. MGB’s HaH program offers clinical laboratories with new opportunities to provide mobile phlebotomy services to the health system’s Hospital-at-Home patients. (Photo copyright: Mass General Brigham.)
Hospital-at-Home
Proponents of HaH call it a “sustainable, innovative, and next-generation healthcare model. [It is] person-centered medical care that keeps patients out of the hospital, away from possible complications, and on to better outcomes,” RamaOnHealthcare reported.
Some of the biggest payoffs of HaH include:
• Cost Savings: Anne Klibanski, MD, President and CEO, MGB, described the HaH program as “a way the health system could stay afloat and thrive amid financial challenges affecting the industry, with lower costs and better outcomes for patients at home,” Becker’s Hospital Review reported.
• Increased Capacity: Having an HaH program can help alleviate bed shortages by treating many conditions in patient’s homes rather than in the ER. “The program … typically treats patients with conditions like COPD flare-ups, heart failure exacerbations, acute infections and complex cellulitis,” Becker’s reported.
“It’s not typically comfortable to be cared for in the emergency room,” said O’Neil Britton, MD, MGB’s Chief Integration Officer, at WMIF.
• Decreased Staff Exhaustion: “Clinicians have described getting an extra level of joy from treating patients at home,” said Jatin Dave, MD, CMO, MassHealth, at WMIF. He added that this could provide one solution to healthcare burnout, Becker’s noted.
• Lab Connection: Clinical laboratories have the opportunity to meet the need for mobile phlebotomists to draw blood specimens from HaH patients in their homes.
• Patient Satisfaction: “The data suggests that for populations studied in multiple areas, [HaH] is a safe service with high-quality care, low readmission rates, low escalation rates, low infection rates and—bottom line—patients love it.” Adam Groff, MD, co-founder of Maribel Health, told RamaOnHealthcare.
HaH Program Going Forward
Britton told the WMIF audience that MGB hopes to “expand the program for surgery, oncology, and pain management patients, recently admitting its first colorectal surgery patient,” Becker’s reported.
However, the future of MGB’s HaH program is not assured. “The Centers for Medicare and Medicaid Services (CMS) waiver to provide acute hospital care at home expires at the end of 2024. A bill to extend the program recently passed a House committee,” Becker’s reported.
Dave said at WMIF that he “hopes the home will one day provide a ‘single infrastructure’ for all levels of care: from primary to inpatient care to skilled nursing,” Becker’s Hospital Review noted, adding, “The home is where, in the long run, we can have this full continuum.”
Overall, this can be a snapshot of where the HaH movement in the US is currently at, with the Mass General Brigham example showing that this mode of healthcare is delivering results and helping patients. Clinical laboratories across the nation should track efforts by hospitals and health systems in their areas to establish and expand hospital-at-home programs.
Findings could lead to new therapies and clinical laboratory biomarkers for detecting and defeating antibiotic-resistant bacteria
Once again, new research shows that human gut bacteria (microbiota) may be useful in fighting antibiotic-resistant bacterial infections. The study findings could provide new therapeutics and clinical laboratory biomarkers for diagnosing and treating severe gastrointestinal disorders.
Antibiotic-resistant bacterial infections often appear in patients with chronic intestinal conditions and in those with long-term antibiotic use. Enterobacteriaceae is a large family of gram-negative bacteria that includes more than 30 genera and over 100 species.
“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, PhD, a computational postdoctoral researcher at the Broad Institute and co-first author of the paper, in the news release.
“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she added.
The researchers identified a way to treat patients infected by antibiotic-resistant strains of bacteria that does not involve antibiotics. Should further research validate these early findings, this could be a viable approach to treating patients with this condition.
“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said Ramnik Xavier, MD (above), director of Broad Institute’s immunology program, co-director of the infectious disease and microbiome program, and co-senior author on the study, in a news release. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.” Clinical laboratories that test for intestinal conditions caused by antibiotic resistance will want to follow the Broad Institute’s research. (Photo copyright: Broad Institute.)
Suppressing Growth of Antibiotic-resistant Bacteria
To perform their research, the scientists isolated about 40 strains of bacteria from the stools of five healthy fecal donors. They then used those stool samples in fecal microbiota transplants to treat mice that had been infected with either Escherichia coli (E. coli) or Klebsiella, both forms of Enterobacteriaceae. The scientists tested different combinations of the 40 strains and identified 18 that suppressed the growth of Enterobacteriaceae.
“Antibiotic-resistant Enterobacteriaceae such as E. coli and Klebsiella bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that Enterobacteriaceae also perpetuates inflammation in the intestine and infection by other microbes,” the Broad Institute news release notes.
The researchers discovered that Klebsiella changed the gene expression in carbohydrate uptake and metabolism in the Klebsiella-infected mice that were treated with the 18 beneficial strains. The gene expression included the downregulating of gluconate kinase and transporter genes, which revealed there is increased competition among gut bacteria for nutrients.
When combined, these 18 strains alleviated inflammation in the guts of the treated mice by depriving the harmful gut bacteria of carbohydrates. This non-antibiotic approach also prevented harmful bacteria from colonizing in the gut.
“In partnership with the Broad’s Metabolomics Platform, led by senior director and study co-author Clary Clish, PhD, they analyzed samples from pediatric patients with ulcerative colitis, looking for the presence of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin,” the study authors wrote in Nature.
“Together, the findings suggest that Enterobacteriaceae processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with Enterobacteriaceae for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria,” the scientists concluded.
Promising New Bacterial Therapies
This research could ultimately lead to the development of fecal microbiota transplants for individuals to eradicate antibiotic-resistant bacteria in a more objective and specific manner, with fewer side effects than current treatments.
“Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection,” the scientists wrote in Nature.
According to the news release, they plan to continue research to “uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.” The team hopes to discover how different bacteria compete with each other, and to develop microbial therapeutics that improve gut microbiome and curb bacterial infections.
More studies are needed to prove the efficacy of this type of fecal bacterial treatment. However, this research demonstrates how using nano processes enabled by new technologies to identify the actual work of proteins, RNA, and DNA in the body cheaply, faster, and with greater precision, will open doors to both therapeutic and diagnostic clinical laboratory biomarkers.
