Findings may lead to new clinical laboratory testing and treatments for Parkinson’s patients
Gut bacteria have repeatedly been proven to perform critical roles in the development of certain diseases. And many clinical laboratory tests use human microbiota as biomarkers.
Now, researchers at Nagoya University Graduate School of Medicine in Japan have discovered a link between microbes in the gut and the brain. The connection may play a part in the development of Parkinson’s disease, according to a Nagoya University news release.
The researchers found that a reduction in the genes responsible for synthesizing riboflavin (vitamin B2) and biotin (vitamin B7) may increase the likelihood of developing Parkinson’s.
They also determined that the lack of these genes may lessen the integrity of the intestinal barrier that prevents toxins from entering the bloodstream causing the inflammation often seen in Parkinson’s patients.
“Supplementation therapy targeting riboflavin and biotin holds promise as a potential therapeutic avenue for alleviating Parkinson’s symptoms and slowing disease progression,” said lead researcher Hiroshi Nishiwaki, PhD, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, in a news release. (Photo copyright: Nagoya University.)
Key Deficiencies in Parkinson’s Patients
According to the Parkinson’s Foundation, nearly one million people in the US are living with Parkinson’s and that number is expected to increase to 1.2 million by the year 2030. Approximately 90,000 new cases of Parkinson’s are diagnosed in the US each year, and more than 10 million people are living with the disease worldwide.
To perform their research, the Nagoya University team analyzed stool samples from 94 Parkinson’s patients from Japan, the US, Germany, China, and Taiwan. They also included 73 relatively healthy controls from Japan. They then used shotgun sequencing (a laboratory technique for determining the DNA sequence of an organism’s genome) to gain a better understanding of the microbial community and genetic makeup of each sample.
The scientists discovered a decrease in B2 and B7 vitamins in patients diagnosed with Parkinson’s. B vitamins promote the production and functions of short-chain fatty acids (SCFA) and polyamines.
“Supplementation of riboflavin and/or biotin is likely to be beneficial in a subset of Parkinson’s disease patients, in which gut dysbiosis plays pivotal roles,” the authors wrote in NPJ-Parkinson’s Disease.
The examination of fecal metabolites in Parkinson’s patients revealed a reduction in both components.
“Deficiencies in polyamines and SCFAs could lead to thinning of the intestinal mucus layer, increasing intestinal permeability, both of which have been observed in Parkinson’s,” said Hiroshi Nishiwaki, PhD, a professor at Nagoya University Graduate School of Medicine and a lead researcher for the study, in the news release.
“This higher permeability exposes nerves to toxins, contributing to abnormal aggregation of alpha-synuclein, activating the immune cells in the brain, and leading to long-term inflammation,” he added.
The team surmises that the weakened protective layer in the gut exposes the intestinal nervous system to more of the toxins people experience in everyday life, such as chemicals, pesticides, and herbicides. These types of toxins lead to the overproduction of alpha-synuclein fibrils. These molecules are aggregates of the α-synuclein protein that form into long, thread-like structures which are primarily found in the brains of individuals with neurodegenerative diseases like Parkinson’s.
Alpha-synuclein fibrils amass in dopamine-producing cells in the brain and increase the type of inflammation that leads to the debilitating motor skills and dementia symptoms of Parkinson’s.
Precision Medicine Analysis Suggested
Due to their research, the team proposes that high doses of vitamin B may help reduce the damage of toxins on the gut microbiome, help protect against neurodegenerative diseases like Parkinson’s, and aid in the creation of personalized therapy plans for patients.
“We could perform gut microbiota analysis on patients or conduct fecal metabolite analysis,” Nishiwaki noted. “Using these findings, we could identify individuals with specific deficiencies and administer oral riboflavin and biotin supplements to those with decreased levels, potentially creating an effective treatment.”
The results of the Nagoya University study illustrate the importance of a healthy gut microbiome in the prevention of disease. Altering the bacterial level in the gut may enable doctors to stave off the progression of neurodegenerative illnesses like Parkinson’s disease.
Researchers tracked “excess deaths” among adults aged 25 to 44 years and found disparate causes to blame
Studies conducted at the University of Minnesota and Boston University found that mortality rates among young adults have risen substantially since 2010 due to a variety of factors, pointing to a possible “mortality crisis” as they get older.
The researchers used data from the Centers for Disease Control and Prevention (CDC) and US Census Bureau to analyze nearly 3.4 million deaths in the US between 1999 and 2023 among adults aged 25 to 44 years, according to a Boston University press release.
They then used mortality data from 1999 through 2010 to project expected death rates for the later years and compared those projections to the actual post-2010 mortality rate to calculate the number of “excess deaths,” defined as “those [deaths] above what had been projected for a given period.”
“What we didn’t expect is how many different causes of death have really grown for these early adults,” said study lead author Elizabeth Wrigley-Field, PhD, of the University of Minnesota, in a U of M pressrelease. “It’s drug and alcohol deaths, but it’s also car collisions, it’s circulatory and metabolic diseases—causes that are very different from each other. That tells us this isn’t one simple problem to fix, but something broader.”
From that perspective, clinical laboratories could be part of the solution in tracking down these early conditions and steering young patients towards healthier outcomes.
“The rise in opiate deaths has been devastating for Americans in early and middle adulthood,” said sociologist Elizabeth Wrigley-Field, PhD, of the University of Minnesota in a press release. (Photo copyright: University of Minnesota.)
One-Two Punch
In 2019, excess mortality amounted to 41.7 deaths per 100,000 population, nearly 35% higher than expected, the researchers wrote. Then, in 2021 during the pandemic, excess mortality from all causes was nearly three times higher: 116.2 deaths per 100,000 population. In 2023, excess mortality decreased, but only to 79.1 deaths per 100,000 population.
“As a result, early adult mortality was 70.0% higher in 2023 than it would have been had pre-2011 trends continued,” the researchers wrote in Jama Network Open.
Speaking with Healio, Wrigley-Field described a “one-two punch that these age groups have seen: first, rising mortality since 2010; then the pandemic, only partially recovered from.”
Five causes accounted for nearly 75% of the excess deaths in 2023, the researchers found:
Drug poisoning, such as opiate overdoses (31.8%)
Residual natural causes (16%)
Transport-related deaths, such as motor vehicle accidents (14.1%)
Alcohol-related deaths (8.5%)
Homicide (8.2%)
The researchers also found that cardiometabolic conditions accounted for 9.2% of excess deaths. These include metabolic, circulatory and endocrine, and nutritional conditions, they noted.
Study co-author Andrew Stokes, PhD, of Boston University characterized the latter as a red flag, according to the Boston University press release. “Usually, it takes a lifetime to manifest cardiovascular disease and related mortality,” he said.
“Our findings underscore the urgent need for comprehensive policies to address the structural factors driving worsening health among recent generations of young adults,” he said in the U of M press release. “Solutions may include expanding access to nutritious foods, strengthening social services, and increasing regulation of industries that affect public health.”
Policy Measures
In their paper, the researchers suggested that policymakers should pay more attention to underlying causes such as opioid use, alcohol consumption, and traffic safety, as well as “ongoing consequences of the COVID-19 pandemic—which may be expressed in causes of death related to long-term consequences of infection, medical disruption, and social dislocation—and to deleterious health trends that predated it.”
“Individuals might not necessarily be able to reverse those factors, or their consequences, on their own, but public health collectively has been very successful at improving health through policies like tobacco regulation, to name one example,” Wrigley-Field told Healio.
She added that “the cardiometabolic causes of death stand out because these are really a bellwether of population health. These causes tend to be very responsive to the fundamentals of healthy living: healthy food, exercise, sleep, limited exposure to tobacco and air pollution, and limited experience of excessive stress.”
Young adults have also been dealing with the “expansion of industries that affect public health—processed foods and beverages, prescription drugs and OxyContin, alcohol, combined with this creeping effect of the obesity epidemic,” Stokes said.
He added: “These are the ages, 25 to 44, in which behaviors become entrenched and life course risks start to develop. And if we’re seeing this excess mortality in this generation now, it’s also an indication of what may happen to population health as a whole in decades ahead as this generation ages.”
This information can inform physicians and laboratorians about what diagnostic tests to consider for young people showing symptoms, even if their ages traditionally don’t indicate a chronic condition.
Hospitals in 38 states confirmed patient infections of the dangerous, drug-resistant fungus
Rapidly spreading Candida auris fungus is once again showing up in hospitals throughout the United States, with multiple cases confirmed in Georgia and Florida. Hospital laboratories and pathology departments are encouraged to take advantage of CDC resources to help in the diagnosis of this deadly pathogen.
Candida auris (C. auris) spreads between patients in hospital settings, is resistant to anti-fungal medications, and can cause severe illness, according to the Centers for Disease Control and Prevention (CDC). Tracking data from CDC’s National Notifiable Diseases Surveillance System found 4,514 new clinical cases of C. auris in the US in 2023.
“The number of clinical cases has continued to increase since the first US case was reported in 2016,” said the CDC of past outbreaks of C. auris. “Based on information from a limited number of patients, 30–60% of people with C. auris infections have died. However, many of these people had other serious illnesses that also increased their risk of death.” The fungus has been spreading at a high rate from 2016-2023 with several cases cropping up recently in Georgia.
According to representatives from the Georgia Department of Public Health, “the state has seen over 1,300 cases as of the end of February,” WJCL reported.
The Hill reports a significant recent increase in the spread of the fungus in all but 12 states. Though the number of cases in each state remains small, the overall percentage of increased cases is large and growing.
And a study conducted at Jackson Health System in Miami, Fla., and published in the American Journal of Infection Control, found that “The volumes of clinical cultures with C. auris have rapidly increased, accompanied by an expansion in the sources of infection.”
“If you get infected with this pathogen that’s resistant to any treatment, there’s no treatment we can give you to help combat it. You’re all on your own,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. (Photo copyright: University of South Carolina.)
CDC Recommendations
The deadly fungus was first detected in 2016 in US hospitals, and the number of cases in hospital patients has grown every year based on CDC data from 2023. Invasive medical procedures can provide a gateway for C. auris to infect patients, and the immunosuppressed nature of these patients can lead to further complications.
Invasive procedures that could expose a patient to C. auris include the placing of breathing and feeding tubes, and the insertion of vein or urinary catheters.
“We’ve had four people at one time on and off over the past few months, and in years past, it was unusual to have one or even two people with Candida auris in our hospital,” Timothy Connelly, MD, told WJCL about the spread of the fungus at Memorial Health in Savannah, Ga.
Cases have also rapidly increased in Miami according to the Jackson Health System study. The researchers found that, “The volumes of clinical cultures increased every year and infection sources expanded.”
The CDC considers C. auris “an urgent antimicrobial resistance threat” based on the severe risk an infected patient can face. “The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said Meghan Lyman, MD, in a CDC news release.
Fungal Infection is Difficult to Treat and Diagnose
C. auris has been shown to be resistant to antifungal medications, making it an acute threat to ill patients. And since it tends to infect already sick patients, it can be difficult to detect because symptoms of infection can be generic, such as fever or chills.
The fungus is also adept at surviving on hospital surfaces.
“It’s really good at just being, generally speaking, in the environment,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. “So, if you have it on a patient’s bed for example, on the railing, and you go to wipe everything down, if in whatever way maybe a couple of pathogens didn’t get cleared, then they’re becoming resistant. And so over time, they can kind of grow and populate in that hospital environment.”
CDC Resources to Help Identify C. auris
C. auris also can be misidentified with other candida species fungi. The CDC recommends identification using a diagnostic device “based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF).” The CDC also recommends using supplemental MALDI-TOF databases and molecular methods to help distinguish C. auris from other candida.
Prompt clinical laboratory diagnosis is extremely important to stem outbreaks as they become more frequent in hospital settings. The CDC offers resources for hospital pathology departments to aid in screening and detection.
“I think we need to do a better job of predicting,” Nolan told Nexstar. “Moving forward [we need] more funding to support quality surveillance of these potential infectious strains so that we can know in advance, and we can do a better job of stopping disease spread before it becomes a problem.”
According to the CDC, the fungus typically spreads in hospital settings and is not known to affect healthy people.
However, effective communication can bring more harmony to medical lab managers and scientists when it comes to compliance
Depending on how lab professionals view it, clinical laboratory regulations can be characterized as a series of checklists to fill out or an opportunity to grow an organization.
Leaning into the latter option will preserve regulatory compliance while also ensuring the operational health of the clinical laboratory.
At the Lab Manager Leadership Summit, Kelly VanBemmel, MS, MB(ASCP)CM (above) pressed attendees to open the lines of communication between bench scientists and lab managers when it comes to clinical laboratory regulations. (Photo copyright: Scott Wallask.)
‘There’s a Gap’ in How Both Sides View Regulatory Compliance
VanBemmel spent her presentation aiming to bridge the rift between how bench scientists look at clinical laboratory regulations compared to the views of medical lab managers.
“There’s a gap between how staff experience regulations and how management does,” she noted. “Staff typically think of compliance as a checklist to do their jobs.” Managers, however, need to understand a wider compliance picture. She illustrated her point by comparing views on the following regulatory bodies.
Staff understand that the FDA clears tests and devices for use in non-research environments, though not all consumables or equipment are in that setting.
Managers understand that the FDA develops rules and guidance for CLIA complexity categorization.
Communication Leads to Common Ground with Clinical Laboratory Regulations
Given the above differences among managers and staff, VanBemmel explained that both sides must frequently talk to each other to fill in the missing details.
“When you’re in the thick of regulations, communication becomes critical,” she said.
For example, bench staff may feel it is solely their manager’s responsibility to comply with clinical laboratory regulations. Savvy lab leaders will point out non-compliant conditions—such as diagnostic analyzer malfunctions and sample cross contamination—over which bench staff have direct control, helping workers better understand their responsibility when it comes to compliance.
On the other hand, lazy communication from managers to their bench scientists can stunt compliance efforts. She recalled a prior supervisor who often answered questions about regulations by asking: What does the standard operation procedure state?
“That answer wasn’t particularly helpful,” VanBemmel recalled. “That made me think that my supervisor didn’t understand nuance.”
Thorough communication builds greater trust, and seasoned clinical laboratory professionals of all ranks will quickly recognize the compliance benefits when the worker-manager relationship gels.
Endemic in the Amazon region, recent spread of the disease caused the CDC to issue recommendations to travelers who develop symptoms after visiting certain countries
Anatomic pathologists, microbiologists, and clinical laboratories active in infectious disease testing will want to stay informed about the worldwide progression of the Oropouche virus. The infectious pathogen is spreading beyond the Amazon region (where it is endemic) into more populated areas—including the US—and possibly being transmitted in novel ways … including through sexual activity.
The virus primarily spreads to people through biting small flies called midges (a.k.a., no-see-ums), according to a CDC Health Alert Network (HAN) Health Advisory, which added that mosquitoes can also spread the disease.
Oropouche infections, the CDC said, are occurring in Brazil, Bolivia, Peru, Columbia, and Cuba. Cases identified in the US and Europe seem to be among travelers returning from those countries. Reported cases also include deaths in Brazil and cases of mother-to-child (vertical) transmission.
There is “an increase in Oropouche virus disease in the Americas region, originating from endemic areas in the Amazon basin and new areas in South America and the Caribbean,” CDC noted in its Health Advisory.
Though de Oliveira notes that a global outbreak is not yet expected, researchers are nevertheless raising the alarm.
“The challenge is that this is such a new disease that most clinicians—including infectious disease specialists—are not aware of it and we need to make more patients and healthcare providers aware of the disease and increase access to diagnostics so we can test for it,” said David Hamer, MD (above), infectious disease specialist and professor, global health, at Boston University School of Public Health, in an NPR article. “Over the next year, we are going to learn a lot more.” Pathologist, microbiologists, and clinical laboratories will want to keep an eye on the spread of the Oropouche virus. (Photo copyright: Boston University.)
Risks to Pregnant Women, Seniors
Research published in The Lancet Infectious Diseases estimates up to five million people in the Americas are at risk of exposure to the Oropouche virus. The authors also pointed out that cases in Brazil swelled from 261 between the years 2015 to 2022 to 7,497 by August 2024.
About 60% of people infected with Oropouche have symptoms such as fever, chills, headache, muscle aches, and joint pains, according to the CDC Health Advisory, which added that the symptoms generally appear three to 10 days after exposure.
Those with the highest risk of complications from the disease, according to the CDC, include pregnant women, those over age 65, and people with medical conditions such as:
“The geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents in the Americas,” an additional paper in Emerging Infectious Diseases noted.
“Healthcare providers should be aware of the risk of vertical transmission and possible adverse impacts on the fetus including fetal death or congenital abnormalities,” CDC said in an Oropouche Clinical Overview statement.
“There have been a few cases of maternal to fetal transmission, and there are four cases of congenital Oropouche infections that have been described—all of which led to microcephaly, which is a small head size,” David Hamer, MD, infectious disease specialist and professor global health, Boston University School of Public Health, told NPR.
Diagnostic Testing at Public Labs
Clinical laboratories and physicians should coordinate with state or local health departments for Oropouche virus testing and reporting.
People should consider Oropouche virus testing if they have traveled to an area with documented or suspected cases, have symptoms including fever and headache, and have tested negative for other diseases, especially dengue, according to CDC.
Taking Precautions after Sex
“This [possibility of sexual transmission] brought up more questions than answers,” Hamer told NPR, adding, “we know now is that sexual transmission could happen.”
Though no documented cases of sexual transmission have been recorded, the CDC nevertheless published updated interim guidance, “recommending that male travelers who develop Oropouche symptoms after visiting areas with Level 1 or 2 Travel Health notices for Oropouche to ‘consider using condoms or not having sex for at least 6 weeks’ from the start of their symptoms,” NPR reported.
“Because stillbirths, birth defects, and severe complications and deaths in adults have been reported, CDC is providing interim recommendations on preventing possible sexual transmission based on what we know now,” the CDC stated.
Clinical laboratory leaders working with infectious disease colleagues can help educate physicians and the community about the Oropouche virus and the need to prevent bites from midges and mosquitoes by using, for example, Environmental Protection Agency (EPA) registered insect repellant.
Diagnostics professionals will want to stay abreast of developing Oropouche cases as well as changes to or expansion of clinical laboratory testing and reported guidance.
