Hidden gut defect that may explain why IBD keeps coming back

 Researchers have identified early molecular warning signs of inflammatory bowel disease that may appear before symptoms and remain active even when patients seem to be doing well.

The study, led by WEHI in partnership with the Royal Melbourne Hospital, uncovered a hidden defect in intestinal cells that can make them vulnerable to damage. The problem was still detectable in some patients whose disease appeared to be well controlled.

Published in Science, the findings may help explain why people with inflammatory bowel disease can experience sudden flare-ups even after reaching remission.

Key findings

WEHI researchers identified a 'smoldering' molecular defect in gut cells from people with inflammatory bowel disease.

The defect involves abnormal cell death and could be detected even in patients whose disease was under good control.

The work, carried out through a broad collaboration with the Royal Melbourne Hospital, could eventually lead to earlier prediction of flare-ups, more precise monitoring and treatment tailored more closely to individual patients.

A hidden problem in intestinal cells

Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is a chronic condition that affects around 180,000 Australians.

People with IBD can experience serious symptoms including rectal bleeding, abdominal pain, diarrhea, fatigue, and weight loss.

Modern therapies can help many patients achieve remission, but diagnosing and managing IBD remains challenging.

The disease often alternates between periods when symptoms are controlled and sudden flare-ups that can become severe enough to require hospital care.

Study co-author Dr. Andre Samson said the researchers discovered that intestinal cells could remain vulnerable even when patients felt well, and their disease appeared stable.

"Once you've got the diagnosis, IBD doesn't go away. Even if you become symptom-free on the current treatments, we know there's a likelihood you're going to have a flare or relapse," said Dr. Samson.

"What we found in patient samples was that intestinal cells are primed to die. Even in patients with essentially no symptoms, there's still this persistent problem sitting there."

Cell death may help drive IBD

The results challenge the assumption that cell death in IBD is simply damage caused by inflammation. Instead, the researchers say abnormal cell death may be involved in helping drive the disease itself.

The defect was already present during the earliest stages of disease activity, including in patients with clinically mild IBD. Detecting it required detailed molecular analysis.

Study co-author Professor James Murphy said the discovery revealed a 'smoldering' molecular problem and encouraged the researchers to focus more closely on what happens at the beginning of the disease process.

"Most people have been focusing on the major clinical problem, when someone comes to hospital with severe gut inflammation," Prof Murphy, a WEHI deputy director and lab head, said.

"We've gone to the other end of the spectrum and looked at gut tissue that doesn't have clear signs of active disease. What we're finding is this molecular defect happening very early in disease progression - one of the first dominoes to fall."

Human tissue reveals clues to future flare-ups

The research relied entirely on human tissue and patient-derived organoids.

Working with clinicians from the Royal Melbourne Hospital, the team collected around 900 biopsies from 80 people with and without IBD. Researchers used those samples to grow organoids, lab-grown tissues derived from patients, allowing them to investigate the disease directly in human cells.

Study co-author Professor Edwin Hawkins, head of the Colonial Foundation Diagnostics Center where samples were analyzed, said the size and nature of the patient group were important strengths of the research.

"While cell death has been implicated in IBD for a long time, how it arises in humans has remained unclear, probably because most studies rely on mouse models which often do not accurately mimic the human condition," Prof Hawkins, a WEHI lab head, said.

"Our study is based on human tissue and patient biopsies."

Researchers then tracked the patients for more than two years. They found that people showing stronger intestinal cell death signaling were also more likely to experience a relapse.

Toward earlier IBD detection

IBD can behave very differently from one person to another, making it difficult to know who will respond to a particular treatment or who is most likely to relapse.

Study co-author Dr. Jiyi Pang said the newly identified molecular signals could eventually help scientists develop more precise tools for monitoring patients and selecting treatments based on the biology of an individual's disease.

"The causes of IBD are largely unknown and quite variable," Dr. Pang said.

"Using mini-intestinal organoids grown in a dish and by working alongside a diverse team of researchers and clinicians, we uncovered the inflammatory signals responsible for this cell death response."

"We now have the hallmarks of what underlies disease at the molecular level. The question is which of those are therapeutically actionable and whether they might help us to better match treatments to patients, based on how their disease behaves at a molecular level."

More personalized treatment could follow

Study co-author Dr. Aysha Al-Ani cautioned that the findings are unlikely to produce a new diagnostic test or therapy immediately. However, they provide a foundation for future research into better forecasting tools and potential treatments.

"It opens new avenues for different prognostic tools, using more sophisticated and refined methods than are currently used clinically," Dr. Al-Ani said.

"The ethos behind IBD therapy is to reduce the frequency and severity of flares, halting disease progression and improving patients' lives. More sensitive molecular detection may help us keep patients in deep remission for longer and introduce new treatments."

Source: ScienceDaily

Scientists solve a 50-year mystery and discover a new human blood group

 More than half a century after scientists first encountered a mysterious marker on human red blood cells, researchers finally traced it to its genetic source. The breakthrough established MAL as a human blood group system and gave doctors a new way to identify the exceptionally rare people whose blood lacks the AnWj antigen.

The work was led by scientists at NHS Blood and Transplant in Bristol, including researchers from the International Blood Group Reference Laboratory (IBGRL), together with colleagues at the University of Bristol. Their findings solved a puzzle dating back to 1972 and could help prevent dangerous transfusion reactions in a small number of patients.

Although most people are familiar with the ABO and Rh blood groups, those are only part of a much larger biological system. Red blood cells carry hundreds of different molecules on their surfaces. Many of these molecules act as antigens, markers that the immune system can recognize.

For most transfusions, ABO and Rh compatibility receive the most attention. But in patients with unusual antibodies or rare blood types, matching some of these lesser-known antigens can become crucial.

A Blood Marker Found in More Than 99.9% of People

The AnWj antigen was discovered in 1972, but for decades scientists did not know which gene produced it or which protein carried it on red blood cells.[1]

More than 99.9% of people are AnWj positive. For the tiny minority who are AnWj negative, however, the distinction can matter enormously.

If an AnWj negative person develops antibodies against AnWj and then receives AnWj positive blood, those antibodies can attack the transfused red blood cells. In some circumstances, that can trigger a potentially serious transfusion reaction.

There are also two very different reasons someone can lack the antigen. In most cases, AnWj expression appears to be suppressed because of an underlying hematological disorder or certain cancers.[2] Much more rarely, a person is born without the antigen because of an inherited genetic change.

Only a handful of people with this inherited form had ever been identified, making the mystery especially difficult to investigate.

The Genetic Clue Was Hidden in MAL

To find the source, the researchers turned to whole exome sequencing. This technique examines the portions of DNA that contain instructions for making proteins, allowing scientists to search across thousands of genes for unusual variants shared by affected individuals.

The analysis pointed unexpectedly to the MAL gene.

The researchers found that people with the inherited AnWj negative phenotype carried homozygous deletions affecting MAL. Homozygous means that the relevant change was present in both copies of the gene, one inherited from each parent.

The MAL gene produces a small membrane protein called Mal. When the team examined red blood cells, people who were AnWj positive produced the full-length Mal protein on their cells, while it was missing from AnWj negative cells.

Five genetically AnWj negative individuals were included in the investigation, including members of an Arab Israeli family.[3] The samples also included blood donated in 2015 by the woman who had been the first AnWj negative person identified in the 1970s.

The researchers did not stop at finding a genetic association. They needed to demonstrate that Mal really was responsible for the antigen.

When scientists introduced the normal MAL gene into laboratory cells, the cells became reactive with AnWj antibodies. Introducing the altered form did not produce the same response. Additional experiments showed that Mal was both necessary and sufficient for expression of the AnWj antigen.

Source: ScienceDaily

Chronic stress may be quietly reshaping your heart

 Chronic stress linked to everyday life may leave a lasting physical mark on the heart, potentially damaging cardiovascular health and shortening lifespan.

That conclusion comes from a study of nearly half a million adults in the UK, led by researchers at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London. The researchers believe it is the largest study of its kind.

Their findings suggest that chronic inflammation, which is associated with lifestyle and socioeconomic circumstances, may contribute to harmful changes in the heart's structure. It was also linked to a greater risk of heart attack and stroke.

Importantly, these changes may begin years before a person notices any cardiovascular symptoms, allowing the damage to build silently over time.

Hidden Inflammation May Change the Heart

Professor Declan O'Regan, British Heart Foundation Chair of Cardiovascular AI at Imperial College London and Head of the Computational Cardiac Imaging Group at the LMS, said: "Our study, which is the largest of its kind, suggests that millions of people could be living with hidden inflammation, which is slowly changing their heart and causing long-term damage - increasing the risk of heart attack and stroke. Chronic inflammation is complicated, but we know it's tied to our health and driven by a range of lifestyle and economic factors - meaning people may be at more risk just because of their surroundings, their economic status, their family's health and their lifestyle."

"But while tackling health inequalities remains an issue, there are things that we can do about inflammation, including reducing risk factors like smoking and obesity."

Chronic inflammation occurs when the immune system remains mildly activated for long periods rather than switching off after an immediate threat has passed. This persistent, low-level immune activity has been associated with several diseases, including cancer and diabetes, and researchers increasingly suspect that it may also play an important role in heart disease.

For the new study, the team examined UK Biobank data from nearly 480,000 adults in the UK. They assessed inflammation using a blood marker called glycoprotein acetyls (GlycA) and combined those measurements with heart imaging and genetic information.

A 43% Higher Risk of Heart Attack and Stroke

People with the highest inflammation levels (the top 20%) had a 43% higher risk of heart attack and stroke than participants with the lowest levels (the bottom 20%).

The researchers also found signs that inflammation was associated with physical remodeling of the heart. People with higher inflammation tended to have thicker heart walls, smaller heart chambers and poorer heart filling - all changes which may develop quietly for years before progressing to heart failure.

Inflammation was also strongly associated with socioeconomic disadvantage and psychological distress. More familiar cardiovascular risk factors, including smoking and excess body fat, were linked to higher inflammation as well.

People whose inflammation remained elevated over time had a 43% greater risk of heart attack and stroke, even when they had no previously existing heart disease.

The findings suggest that inflammation may provide one biological route through which pressures from everyday life, including poverty and mental health problems, can affect the body and increase cardiovascular risk.

Social Factors, Mental Health, and Genetics

Professor Declan O'Regan added, "The surprising thing was how much social factors and mental health are linked to inflammation and damage to the heart -- as well as more well-known risk factors like smoking and inactivity. There was also a strong genetic factor, with some people being naturally more resilient or susceptible to the inflammatory damage that comes from different lifestyles."

The researchers emphasize, however, that genetic susceptibility or difficult life circumstances do not make heart disease inevitable. There are still opportunities to reduce persistent inflammation and lower cardiovascular risk.

The analysis also highlighted inflammatory proteins in the interleukin-1 and TNF families as possible contributors to the observed heart damage.

Several of these proteins are already being targeted by drugs being tested in clinical trials. That raises the possibility that anti-inflammatory therapies could eventually help prevent cardiovascular disease before symptoms begin.

Blood Tests Could Help Identify People at Risk

The researchers also suggest that inflammation blood tests could potentially be combined with genetic risk scores to identify people who may benefit most from early intervention.

Source: ScienceDaily

That fresh cleaning smell could be filling your home with nanoparticles

 A room that smells like citrus, pine, or flowers is often associated with cleanliness. Those familiar scents, however, can signal chemical reactions taking place in the air.

Research led by Brandon Boor at Purdue University found that fragrance compounds released by both conventional cleaners and botanical essential oil-based products can rapidly react indoors and generate nanoparticles. If inhaled, some of these extremely small particles can penetrate deep into the lungs.

The researchers say exposure can be reduced by choosing unscented products, improving ventilation with exhaust fans or open windows, and avoiding devices that generate ozone while scented cleaning products are being used.

The researchers presented their results at the fall meeting of the American Chemical Society (ACS) during the "Healthy Indoor Spaces: Bridging the Microbiome and Chemistry" symposium in McCormick Place.

"Importantly, cleaning removes viruses and bacteria from surfaces, but it can also generate invisible air pollution. There's no visible dust or smoke in the air, but these particles are forming." -- Brandon Boor

Cleaning Can Create Invisible Nanoparticles

"We showed that indoor ozone reactions with fragrances from cleaning produce nanoparticles that carry a respiratory dose comparable to, or greater than, what you would experience from standing outside along a busy road," says Boor, an Assistant Professor of Civil and Construction Engineering at Purdue University who studies indoor air quality. "The particles are different in terms of their composition, but the total dose can be higher. You're not seeing smoke, dust, or haze in the air. Instead, you think the air smells great so it must be clean."

Boor began investigating how cleaning agents and chemical disinfectants affect indoor environments during the COVID-19 pandemic with his colleague Nusrat Jung, a Purdue Assistant Professor of Civil and Construction Engineering. One feature quickly stood out: many of the products people use to clean and disinfect indoor spaces contain strong fragrances.

"That's often to create a pleasant smellscape in the indoor space," says Boor. "But clean air should not smell like highly concentrated citrus fruit. It should not really smell of anything."

Scientists who study the atmosphere have long known that compounds released by plants can react with ozone. Terpenes such as pinene from pine trees, for example, can participate in reactions that generate tiny airborne particles. Over time, those particles can combine and grow until they become large enough to help seed clouds.

That chemistry proceeds relatively slowly in forests because the amount of terpenes in outdoor air is generally low.

Cleaning Products Release High Levels of Terpenes

Indoors, the situation can be very different. Scented cleaners release terpenes when fragrance compounds evaporate from sprayed droplets or cleaned surfaces.

Cleaning liquids commonly contain compounds including pinene, limonene (lemon), thymol (thyme), and linalool (lavender). Their concentrations during cleaning can be far higher than levels typically measured outdoors. Boor says airborne terpene concentrations inside a room during cleaning can rise to tens or even hundreds of times those found in a forest.

To examine what happens under realistic conditions, the researchers tested scented conventional liquid products as well as botanical-containing disinfectant sprays and wipes inside a model home on Purdue's campus.

The small house includes a functional kitchen, wood flooring, and a bathroom, allowing the researchers to recreate ordinary household cleaning activities. Their experiments showed that the same basic chemistry responsible for nanoparticle formation outdoors can occur indoors much more rapidly and at much higher concentrations, with potentially important consequences for human exposure.

Billions or Trillions of Particles Can Form

Routine tasks such as mopping floors, spraying countertops, and wiping surfaces with scented products generate billions or trillions of particles, with the total depending on the product.

Most were nanoparticles or ultrafine particles measuring only 1-30 nanometers across. Because particles this small often fall outside the detection range of at-home air quality monitors, people may have no indication that particle concentrations have risen.

The researchers found that ordinary cleaning can temporarily push ultrafine particle levels above those measured outdoors.

Their tiny size is important from a health perspective. Ultrafine particles can settle throughout the respiratory tract and reach deep regions of the lungs. Once there, they can contribute to irritation and inflammation in the respiratory system. Some may also have the potential to enter the bloodstream.

One of the biggest surprises was the speed of the process. Particle formation and growth occurred within just minutes.

"By the time you finish cleaning up an indoor space, you've already formed a lot of nanoparticles and inhaled them," says Boor.

Ozone Can Intensify Indoor Particle Formation

More recently, Boor and Ernest Blatchley, a Professor at Purdue, studied what happens when scented surface cleaners are used at the same time as germicidal far-UV (UV-C) lamps designed to disinfect indoor air.

The combination created particularly favorable conditions for nanoparticle formation.

The lamps interact with oxygen in the air and produce ozone. During experiments in the tiny home, ozone concentrations increased to roughly 20 to 40 parts per billion. Those levels were comparable to, although somewhat below, the outdoor ozone concentrations measured when the experiments were performed.

With both elevated ozone and high concentrations of terpenes present, nanoparticle production became even more intense. That combination raised additional concerns about the amount of particulate matter occupants could inhale.

How to Reduce Exposure While Cleaning

Boor emphasizes that the goal is to help consumers make informed choices rather than discourage cleaning. Cleaning remains important for removing viruses and bacteria from surfaces, but several simple measures may reduce exposure to the secondary pollution produced during the process.

The researchers recommend:

• Choose low-fragrance or fragrance-free products.
• Avoid applying several scented products in the same cleaning session.
• Run exhaust fans or open windows to ventilate the space.
• Do not simultaneously clean surfaces with scented products while using ozone-generating devices, such as far UV-C lamps.
• 
  
• "Importantly, cleaning removes viruses and bacteria from surfaces, but it can also generate invisible air pollution," says Boor. "There's no visible dust or smoke in the air, but these particles are forming."

Boor thanks all the graduate students who have worked with him in the tiny house experiments along with the support of undergraduate students.

The research was funded by a National Science Foundation Faculty Early Career Development Program (CAREER) grant and the Alfred P. Sloan Foundation.

Title Indoor atmospheric nanoparticle formation from scented cleaning products

Abstract Scented volatile chemical products, including surface cleaning agents and botanical disinfectants, are widely used indoors and represent a major source of reactive organic emissions. These products are routinely applied in homes and workplaces for surface cleaning and disinfection to reduce the presence of viruses and bacteria. However, their role in driving indoor atmospheric chemistry and nanoparticle formation remains poorly constrained. This presentation investigates the impact of scented cleaning product use on airborne nanoparticle nucleation, growth, and human exposure to secondary pollutants in indoor environments. Field and laboratory experiments were conducted in controlled residential and office settings using real-time, high-resolution measurements of volatile organic compounds and nanoparticle size distributions extending to the nanocluster aerosol (1-3 nm) regime. Surface cleaning and disinfection activities produced rapid increases in terpene and terpenoid mixing ratios (10-1,000 ppb), often exceeding levels observed in outdoor forested environments. These compounds reacted with indoor oxidants, particularly ozone, to initiate intense nanoparticle nucleation and growth events. Observed nucleation rates (~105 cm-3 s-1) and condensational growth rates (up to 300 nm h-1) exceeded typical outdoor values by orders of magnitude, resulting in transient indoor nanoparticle number concentrations of 105-108 cm-3. Rapid nanoparticle growth enabled survival to sizes that efficiently deposit throughout the human respiratory system, yielding inhalation dose rates comparable to or exceeding those from primary combustion sources such as traffic emissions. Both conventional and botanical cleaning products generated complex multiphase exposure scenarios involving reactive gases and secondary organic aerosol. These findings identify indoor surface cleaning and disinfection as key drivers of indoor atmospheric nanoparticle formation and highlight the need for improved building ventilation, air cleaning, and product formulation to mitigate exposure to secondary pollutants.

Source: ScienceDaily

These blood thinners may have an unexpected benefit for Alzheimer’s patients

 People who have both atrial fibrillation and Alzheimer's disease may experience slower cognitive decline when treated with newer NOAC blood thinners, according to research from Karolinska Institutet published in the European Heart Journal.

Atrial fibrillation is a common heart rhythm condition in older adults and also affects many people living with Alzheimer's disease. Doctors often prescribe blood thinners to these patients to reduce the chance of blood clots and stroke. Earlier research has suggested that anticoagulant treatment may lower the risk of developing dementia, but far less is known about whether these drugs influence cognitive decline after Alzheimer's disease has already been diagnosed.

"There are reasons to believe that the treatment could have a positive effect on cognition, for example by improving blood flow and reducing small-scale damage in the brain," says Maria Eriksdotter, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, and senior consultant in geriatric medicine at Karolinska University Hospital, who led the study.

Comparing Newer and Older Blood Thinners

Researchers analyzed information from SveDem (Swedish Register for Cognitive Disorders/Dementia), a national quality registry, and included 7,308 people diagnosed with both atrial fibrillation and Alzheimer's disease.

Participants were placed into three matched groups. One group received newer anticoagulants known as NOACs, another was treated with the older blood thinner warfarin (Waran), and the third did not receive any anticoagulant medication.

To track changes in thinking and memory over time, researchers used the standardized Mini-Mental State Examination (MMSE).

Slower Cognitive Decline With NOACs

People taking NOACs showed a significantly slower decline in cognitive function than those treated with warfarin or those who received no anticoagulant medication.

The difference amounted to slightly more than 0.2 MMSE points per year. While that change is relatively small over a single year, the researchers say it could become more meaningful if it continues over a longer period.

"The difference is modest for an individual patient from one year to the next, but over a longer period even such an effect could influence how cognitive function develops. Our findings suggest that NOAC treatment may also be significant for cognition in this patient group," says Nanbo Zhu, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

Lower Risks of Stroke and Other Complications

The potential benefits were not limited to cognition. Compared with people who did not receive anticoagulants, those treated with NOACs also had lower risks of death, stroke, blood clots and fractures.

Source: ScienceDaily

A deadly ebola relative is surging after years in the shadows

 A growing outbreak of the rare Bundibugyo virus in the Democratic Republic of Congo is drawing attention to a broader problem in global health: how to prepare for dangerous diseases that appear only rarely but can still cause deadly outbreaks.

In a review article published in the New England Journal of Medicine, Boston University professor Nancy Sullivan argues that outbreak preparedness needs to extend beyond the infectious diseases that receive the most attention.

A Rare Relative of Ebola

Bundibugyo belongs to the filovirus family, the same group of viruses that includes the much better-known Ebola virus. Despite its potential severity, Bundibugyo has been linked to only two previously recognized outbreaks, one in Uganda in 2007 and another in the Democratic Republic of Congo (DRC) in 2012.

The current outbreak, however, has already surpassed those earlier events in both its trajectory and scale. According to the WHO, 695 confirmed cases and 138 confirmed deaths had been reported in the DRC and Uganda as of June 11.

Sullivan, a professor of biology and virology, immunology & microbiology at Boston University, explains that bringing an outbreak under control depends on several measures working quickly together. These include rapid diagnosis, isolating infected patients, tracing people who may have been exposed, strengthening infection control, and providing supportive medical care.

Those steps become much harder when laboratory resources are limited. In settings where testing capacity is scarce, delays in confirming infections can give the virus more time to spread.

A Severe Hemorrhagic Fever

Bundibugyo can cause a severe form of hemorrhagic fever. Infection can trigger widespread inflammation, damage and failure of the cells lining blood vessels, uncontrolled bleeding, and failure of multiple organs.

The virus spreads through direct contact with infected bodily fluids. That creates particular risks for family members, caregivers, and health workers, especially when patients are being treated in hospitals without adequate infection control. The 2026 outbreak was formally recognized after the death of a nurse.

Another major challenge is that Bundibugyo can initially resemble several far more common illnesses. Symptoms overlap with malaria, typhoid fever, and other diseases, meaning laboratory testing is necessary to confirm an infection.

Testing Delays Can Slow the Response

Laboratory access remains limited in parts of the DRC, Sullivan found, and samples may need to travel considerable distances to reach national reference laboratories. That can turn a critical diagnosis into a lengthy process.

"Delays in specimen collection, transportation and testing can postpone confirmation by days or weeks, which hinders the isolation of infected persons, contact tracing and the initiation of outbreak-control measures," Sullivan wrote.

Those delays can be especially damaging during an outbreak, when identifying cases quickly is essential for separating infected people from others and finding anyone who may have been exposed.

The Risk of Overlooking Rare Viruses

The Bundibugyo outbreak also points to a larger weakness in preparedness strategies that concentrate heavily on the most familiar high-risk pathogens.

For decades, Bundibugyo caused relatively little recognized activity. Its return as a significant threat illustrates how difficult it can be to predict which infectious disease will drive the next major outbreak.

Sullivan has argued that medical countermeasures should be developed more broadly for pathogens capable of causing severe illness or death in humans, rather than focusing only on viruses already known to cause frequent outbreaks.

No Licensed Bundibugyo Vaccine

Considerable progress has been made toward vaccines and other medical countermeasures for the Ebola, Sudan and Marburg viruses. Bundibugyo, however, occurs much less often, and no licensed vaccine or therapeutic has been developed specifically to target it.

There are encouraging signs that vaccines designed against other virus species could offer at least some protection, but Bundibugyo remains an example of a dangerous pathogen for which dedicated medical tools are limited.

Sullivan says preparedness also needs to involve much more than creating diagnostic tests, vaccines and drugs. Health systems must be capable of coordinating quickly when outbreaks spread across borders.

Source: ScienceDaily

Ancient DNA reveals how plague kept returning for 400 years after the Black Death

 The Black Death is best known for the catastrophic wave of plague that swept through Europe between 1347 and 1353, killing millions of people. But the disease did not vanish once that initial disaster passed. Plague returned again and again for more than four centuries, repeatedly disrupting cities, economies, and societies across Europe and surrounding regions.

A study led by researchers at the University of Tartu is now offering a much more detailed look at what happened during those centuries. By analyzing DNA from the plague bacterium preserved in archaeological human remains, scientists were able to reconstruct how the disease spread, evolved, and repeatedly reappeared long after the Black Death.

Ancient DNA Reveals Centuries of Plague

The team reconstructed 26 genomes of Yersinia pestis, the bacterium that causes plague, from human remains recovered at 11 archaeological sites in Estonia, Russia, England, the Netherlands, and Switzerland. The samples date from the fourteenth through the eighteenth centuries, covering a large portion of the period known as the Second Plague Pandemic.

The genetic evidence suggests that plague did not simply survive in one place and repeatedly spread outward from a single source. Instead, the disease appears to have resurfaced in different parts of Europe over hundreds of years, potentially creating several new reservoirs where the bacterium could persist.

Estonia was repeatedly affected. Researchers found signs that plague entered the region multiple times during much of the Second Plague Pandemic, indicating that Estonia's connections with other parts of Europe also helped disease move across long distances.

One of the most striking patterns appeared around 1450-1500. During that period, plague lineages underwent a major expansion and split into three important branches. Those branches may have helped establish new reservoirs of Yersinia pestis in wild rodent populations.

Climate may also have influenced this expansion. The researchers point to the Great Renaissance Drought as one possible factor. Studies of modern plague systems have shown that changes in climate can strongly affect outbreaks among wild rodents, which act as natural hosts for the bacterium.

"We found evidence for repeated introductions of plague into Estonia starting already in the late 14th century and identified several previously unknown genetic lineages, both in urban and rural settings," said senior author Prof. Kristiina Tambets.

Pinpointing Ancient Plague Outbreaks

A major challenge in studying historical pandemics is figuring out exactly when ancient infections occurred.

During the COVID-19 pandemic, researchers could follow individual variants in remarkable detail because genome sequences were usually linked to precise dates. Ancient disease samples rarely come with that kind of information. Archaeological remains are often dated using radiocarbon techniques that can produce time windows spanning many decades or even more than a century.

"With COVID-19, scientists could reconstruct the spread of individual strains extremely well because the genomes came with precise timestamps. For historical pandemics, those timestamps are often missing or may cover more than 100 years, which limits our ability to interpret the genetic data," the main author, Dr. Marcel Keller, explained.

To address that problem, the team developed a method designed to narrow those broad dating ranges. Researchers examined where individual plague genomes appeared on the bacterium's evolutionary tree and used that information to refine the likely dates of many samples.

This allowed them to place ancient infections into a much more precise historical timeline.

The researchers then applied the improved dating approach to 64 previously published plague genomes and 11 newly sequenced genomes. Their work represents the first systematic attempt to connect nearly all plague genomes currently available from the fourteenth to eighteenth centuries with outbreaks described in historical records.

"We were able to improve dating intervals for many samples, which allowed us to connect them to specific plague waves and outbreaks that were recorded in the respective towns or regions by chroniclers," said historian and corresponding author Prof. Philip Slavin.

War Helped Plague Move Across Europe

The genetic record also shows how strongly human activity influenced the spread of plague.

Newly analyzed genomes provide additional evidence linking outbreaks to the Thirty Years' War (1618-1648) and the Great Northern War (c. 1700-1721). Armies, displaced civilians, refugees, and traders frequently traveled along the same routes, creating opportunities for disease to move between regions.

"We see how Yersinia pestis splits into new branches during periods of conflict and spreads along the routes traveled by troops and displaced populations," said senior author Dr. Christiana L. Scheib.

The findings add new detail to plague outbreaks connected with the Great Northern War. During the 1710 siege of Tallinn, for example, the disease killed Swedish and Russian soldiers as well as civilians.

Source: ScienceDaily