Tag Archives: Disease

Microbiology

Causing Highly Contagious Diarrheal Disease – Antibiotic-Resistant Shigella sonnei Strain Detected in France

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The emergence of extensively drug-resistant (XDR) strains of Shigella sonnei has been detected by scientists at the Institut Pasteur’s French National Reference Center for Escherichia coli, Shigella, and Salmonella. Shigellosis, a highly contagious diarrheal disease caused by Shigella bacteria, is prevalent not only in industrializing countries but also in industrialized countries like France, where the researchers have been monitoring its spread for several years.

The analysis of bacterial genome sequencing and case characteristics (with most cases being reported in male adults) indicates that these strains, originally from South Asia, predominantly transmit among men who have sex with men (MSM).

This observation needs to be taken into account by clinicians and laboratories when testing for sexually transmitted infections (STIs) in MSM, and systematic antibiograms should be performed if a Shigella strain is isolated to improve treatment for patients infected with XDR strains. The results were published in the journal Nature Communications.

Shigellosis is a highly contagious diarrheal disease that spreads through fecal-oral transmission. Among the different types of Shigella, Shigella sonnei is the species that mainly circulates in industrialized countries. Shigella sonnei infections can cause short-term diarrhea (3-4 days) that resolves on its own. Antibiotic treatment is, however, necessary for moderate to severe cases (bloody diarrhea, risk of complications) or to prevent person-to-person transmission in epidemic situations. The acquisition of antibiotic resistance mechanisms by Shigella bacteria, therefore, restricts therapeutic options.

In this study, scientists from the National Reference Center for Escherichia coli, Shigella, and Salmonella (CNR-ESS) at the Institut Pasteur demonstrate an increase in antibiotic resistance in S. sonnei isolates collected in France over the past 17 years. The study is based on an analysis of more than 7,000 S. sonnei isolates and epidemiological information gathered in connection with national shigellosis surveillance conducted by the CNR-ESS between 2005 and 2021.

The CNR-ESS analyzes all the bacterial isolates sent by its network of private and public partner laboratories throughout France. Over this period, isolates described as “extensively drug-resistant” (XDR) were identified for the first time in 2015. The scientists then observed that the proportion of XDR isolates, which are resistant to virtually all the antibiotics recommended for treating shigellosis, increased significantly and reached a peak in 2021 when 22.3% of all S. sonnei isolates (99 cases) were XDR.

Genome sequencing revealed that all these French XDR strains belonged to the same evolutionary lineage, which became resistant to a key antibiotic (ciprofloxacin) in around 2007 in South Asia. In several geographical regions of the world, including France, the strains then acquired different plasmids coding for resistance to other first-line antibiotics (especially third-generation cephalosporins and azithromycin).

For severe cases, the only antibiotics that are still effective are carbapenems or colistin, which must be administered intravenously, resulting in more aggressive treatment that requires more complex monitoring in a hospital environment.

XDR isolates were observed in France in various contexts: in travelers returning from South Asia or South-East Asia, during an outbreak at a school in 2017 (more than 90 cases, leading to school closure; the index case had returned from South-East Asia) and in men who have sex with men (MSM). The latter were infected by an epidemic clone that has been spreading throughout Europe since 2020 but has also been found in North America and Australia. This subgroup of XDR strains circulating in MSM was the most widespread, accounting for 97% of XDR strains in France in 2021.

Frequent use of antibiotics in South and South-East Asia, together with repeat treatment for STIs in some people potentially exposed to this risk, increase the likelihood of selection of XDR Shigella strains. Further research is needed to understand the different clinical forms of infection, and especially whether there are asymptomatic forms that might cause the bacteria to spread more widely. Therapeutic trials are also crucial to identify effective oral antibiotics for treating these XDR Shigella strains.

Reference: “Rapid emergence of extensively drug-resistant Shigella sonnei in France” by Sophie Lefèvre, Elisabeth Njamkepo, Sarah Feldman, Corinne Ruckly, Isabelle Carle, Monique Lejay-Collin, Laëtitia Fabre, Iman Yassine, Lise Frézal, Maria Pardos de la Gandara, Arnaud Fontanet and François-Xavier Weill, 28 January 2023, Nature Communications.
DOI: 10.1038/s41467-023-36222-8

Pasteur Institute

Microbiology

“Glow-in-the-Dark” Proteins: The Future of Viral Disease Detection?

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Although there have been significant advancements in diagnostic tests for viral diseases, many highly sensitive tests still rely on complex sample preparation and result interpretation methods, rendering them unsuitable for point-of-care settings or resource-limited areas. However, researchers have now revealed in ACS Central Science a novel, sensitive technique that can analyze viral nucleic acids in just 20 minutes using a one-step process with “glow-in-the-dark” proteins.

Bioluminescence, the scientific phenomenon behind the firefly’s glow, the anglerfish’s radiant lure, and the ghostly blue of phytoplankton-laden shores, is powered by a chemical reaction involving the luciferase protein. This luminescent protein has been integrated into sensors that emit visible light when detecting their target, making them ideal for straightforward point-of-care testing. However, until now, these sensors have not achieved the exceptional sensitivity necessary for clinical diagnostic tests.

The gene-editing technique known as CRISPR could provide this ability, but it requires many steps and additional specialized equipment to detect what can be a low signal in a complex, noisy sample. So, Maarten Merkx and colleagues wanted to use CRISPR-related proteins, but combine them with a bioluminescence technique whose signal could be detected with just a digital camera.

To make sure there was enough sample RNA or DNA to analyze, the researchers performed recombinase polymerase amplification (RPA), a simple method that works at a constant temperature of about 100 F. With the new technique, called LUNAS (luminescent nucleic acid sensor), two CRISPR/Cas9 proteins specific for different neighboring parts of a viral genome each have a distinct fragment of luciferase attached to them.

If a specific viral genome that the researchers were testing for was present, the two CRISPR/Cas9 proteins would bind to the targeted nucleic acid sequences and come close to each other, allowing the complete luciferase protein to form and shine blue light in the presence of a chemical substrate. To account for this substrate being used up, the researchers used a control reaction that shined green. A tube that changed from green to blue indicated a positive result.

When tested on clinical samples collected from nasal swabs, RPA-LUNAS successfully detected SARS-CoV-2 RNA within 20 minutes, even at concentrations as low as 200 copies per microliter. The researchers say that the LUNAS assay has great potential for detecting many other viruses effectively and easily.

Reference: “Glow-in-the-Dark Infectious Disease Diagnostics Using CRISPR-Cas9-Based Split Luciferase Complementation” by Harmen J. van der Veer, Eva A. van Aalen, Claire M. S. Michielsen, Eva T. L. Hanckmann, Jeroen Deckers, Marcel M. G. J. van Borren, Jacky Flipse, Anne J. M. Loonen, Joost P. H. Schoeber and Maarten Merkx, 15 March 2023, ACS Central Science.
DOI: 10.1021/acscentsci.2c01467

The study was funded by the Dutch Research Council | Nationaal Regieorgaan Praktijkgericht Onderzoek SIA (NRPO-SIA) and the Eindhoven University Fund.

American Chemical Society

Microbiology

Streptococcus pyogenes, which is often called group A Streptococcus, infects people around the world. While estimates vary, these …

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Streptococcus pyogenes, which is often called group A Streptococcus, infects people around the world. While estimates vary, these infections could be responsible for the deaths of over half a million individuals every year. The pathogen can also cause an illness known as scarlet fever, which usually occurs in kids between the ages of 5 and 15. Scarlet fever was once a major health threat for children, and there were infection rates as high as 20 percent in the early 20th century. The disease became less of a public health concern until its recent reemergence in the UK, Hong Kong, and mainland China.

Colorized scanning electron micrograph of Group A Streptococcus (Streptococcus pyogenes) bacteria (blue) and a human neutrophil (purple). Credit: NIAID

Isolates taken from patients have shown that S. pyogenes can carry resistance genes that shield it from the effects of antibiotics including tetracycline, erythromycin and clindamycin. These bacteria can also generate powerful toxins, like molecules called SSA and SpeC, known as superantigens, and an enzyme called Spd1.

While S. pyogenes infections are still rare, they can kill as many as 20 percent of people who are infected.

In 2019, a variant isolated in the UK, the so-called M1UK strep A variant, was shown to produce five times more strep A toxins compared to previous strains. The SpeA superantigen generated by this variant can short-circuit host immunity and was once known as the scarlet fever toxin. The M1UK variant also carried a few genetic mutations compared to previous strains, and one of those mutations was located close to the toxin gene. The findings have been reported in Nature Communications.

More research will be needed to know whether this variant has gotten better at moving from one person to another to cause infection.

Strep A is very rare, and the study authors noted that people should not be concerned about this novel variant at this time. Basic hygiene practices, like hand washing, can still protect us from dangerous germs like S. pyogenes. Strep A infections are spread through close contact with infected people, who may be coughing and sneezing. Other symptoms include a rash and fever.

The study authors also noted that these findings have highlighted the importance of developing a vaccine for Strep A infections.

An unrelated study reported in mBio has also revealed a different mutation that occurs in a Strep A variant that increases the production of a toxin called streptolysin O (SLO). SLO can help Strep A survive in the host, evade host immunity, and is destructive to host tissues. Variants that did not express SLO were not as virulent, noted the study authors.

Right now, scientists are working on a Strep A vaccine, as described in the video above.

Sources: Nature Communications, Griffith University, mBio


Carmen Leitch

Microbiology

Infections with many different types of bacteria including Streptococcus pneumonia, Listeria monocytogens, and Neisseria mengitidis can cause bacterial …

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Infections with many different types of bacteria including Streptococcus pneumonia, Listeria monocytogens, and Neisseria mengitidis can cause bacterial meningitis. It’s estimated that every year over 1.2 million cases of bacterial meningitis happen around the world, and without treatment, this deadly disease is fatal to seven of ten people who are sickened by it. Even with antibiotic treatments, three of ten patients die. Survivors are left with issues like chronic headaches, seizures, loss of vision or hearing, and other neurological consequences. New research reported in Nature has revealed how bacteria are able to penetrate the meninges that surround and protect the brain to cause bacterial meningitis. The findings have shown that bacteria use neurons to evade immunity and infect the brain, and the work may aid in the creation of new therapeutics.

A digitally-colorized SEM image depicts of Streptococcus pneumoniae bacteria (lavender), as they were being attacked by a white blood cell (pink). / Credit: CDC/ Dr. Richard Facklam

Right now, antibiotics can help eliminate the bacterial pathogens that cause this illness. But steroids are also needed to control the dangerous inflammation that can occur along with the infection. However, reducing inflammation also weakens the immune response, making it harder to get rid of the infection.

In this research, the scientists used Streptococcus pneumoniae and Streptococcus agalactiae bacteria, which can both cause bacterial meningitis in humans. They determined that when these bacteria get to the meninges, they release a toxin, which activates neurons in the meninges that sense pain. This pain neuron activation could explain why bacterial meningitis patients get horrible headaches, noted the researchers.

The activated pain neurons then release a signaling molecule called CGRP, which binds to a receptor called RAMP1 on the surface of immune cells called macrophages. Once CGRP binds to RAMP1 on macrophages, the immune cells are basically disabled, and they stop responding to bacterial infections like they normally would.

The link between CGRP and RAMP1 on macrophages also stops them from signaling to other immune cells, which allows the bacterial infection to not only penetrate the meninges but to spread infection.

This work was confirmed with the use of a mouse model that lacked the pain neurons that are activated by bacteria. Compared to mice with those neurons, the engineered mice had less severe brain infections when they were exposed to bacteria that cause meningitis. There were also lower levels of CGRP in the engineered mice compared to normal mice. The normal mice, however, had higher levels of bacteria in the meninges.

Additional experiments also showed that when mice were treated with drugs that block RAMP1, the severity of the bacterial infection was reduced. Mice treated with RAMP1 blockers were able to clear their infections faster too.

It may be possible to help the immune system clear cases of bacterial meningitis with medications that block either CGRP or RAMP1, potentially in conjunction with antibiotics. There are already drugs that can do this, and they are generally used to treat migraine.

Sources: Harvard Medical School, Nature


Carmen Leitch

Microbiology

Though the COVID-19 pandemic has waned, SARS-CoV-2 is still with us, and we still need diagnostic tests. Scientists …

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Though the COVID-19 pandemic has waned, SARS-CoV-2 is still with us, and we still need diagnostic tests. Scientists have been improving those tests in several ways. Researchers are developing a test that can rapidly diagnose new COVID-19 infections within hours of exposure. A combination flu and COVID-19 test has recently been approved by the US Food and Drug Administration (FDA) and is now available to consumers for use at home. A COVID-19 home test with greater sensitivity has also been created and will hopefully reach the market soon.

Image credit: Pixabay

Typical COVID-19 tests identify viral particles in swabs of the nostrils, throat, and/or cheeks. But those tests are best used during certain windows, and they can miss active infections when there isn’t much viral material available because a person is asymptomatic, or the infection has not yet set in and begun to replicate robustly. A totally new type of test uses a different approach, and aims to detect the immune response to the virus. The work has been published in Cell Reports Methods.

A viral infection activates the expression of a variety of immune genes, which are transcribed into mRNA molecules. The test detects certain levels of those mRNA molecules. The researchers used blood samples collected during the COVID-19 pandemic to validate their results; the test detected COVID-19 infections, even in asymptomatic people, with 98.4 percent accuracy.

More work is still needed to improve the test. For example, it uses blood samples and not nasal swabs. The scientists also need to verify that it can distinguish between different types of viral infections, like COVID-19 and the flu. But the researchers are hopeful that the diagnostic test will be available in the near future.

A combination flu and COVID-19 test is already on the market. The FDA recommends the test for anyone with symptoms of a respiratory tract infection symptoms. It’s called the Lucira COVID-19 & Flu Home test. It does not require a prescription, requires nasal swabs that can be collected by the user at home, and results are available in about 30 minutes.

While samples have to be collected by an adult, the test can be used on anyone older than 2. There is a small risk of false negatives, noted the FDA, so if respiratory infection symptoms exist and the test is negative, people may still want to follow up with their healthcare provider.

Scientists have also developed a much more sensitive test for COVID-19 that can be used at home. The work was reported in ACS Infectious Diseases.

At-home tests change color when an antibody-linked reporter molecule latches onto viral particles in a sample. But that color change is very faint when few viral particles are present. PCR-based tests are good for disease detection because only very small amounts of viral material have to be present; they are then amplified by PCR. But special equipment is needed for PCR.

This new, sensitive test has added an amplification step to a test that can be used at home. A hybridization chain reaction (HCR) boosts the signal of reporter molecules instead. The viral protein gets tagged with a DNA molecule, which can act as a scaffold that more reporter molecules can bind to. Thus, every viral particle triggers the emission of a much stronger signal.

When the sensitive test was compared to tests that are on the market, it was 2.5 times more sensitive than the best, and 100 times more sensitive than the worst. The researchers are now working to get the new test to the market.

Sources: California Institute of Technology, ACS Infectious Diseases, The Associated Press, Simons Foundation, Cell Reports Methods


Carmen Leitch

Microbiology

Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of …

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Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of the world’s population. RA happens when a person’s own antibodies attack joint tissue, causing painful swelling, stiffness, and redness. Some research has suggested that there is a link between RA and gum disease.

Image credit: Pixabay

Gum disease is estimated to affect up to 47 percent of adults, and in the disorder, oral microbes can move to the blood after the gums start to bleed. An increase in disease activity has been observed in RA patients who also have gum disease. Gum disease has been shown to be more common in RA patients who carry a certain type of antibodies, called anti-citrullinated protein antibodies (ACPAs), though ACPAs are often found in the blood of individuals with RA. The presence of ACPAs can often predate the diagnosis of RA by a few years.

A new study investigated the connections between these observations. In this work, the researchers collected blood samples from a small group of ten people with RA, five with and five without gum disease. These samples were collected every week for one year, and the investigators assessed the expression of both human and bacterial genes in those samples.

Certain types of inflammatory immune cells carried gene expression signatures that were associated with the autoimmune flares of arthritis patients who also had periodontal disease, as well as the presence of certain oral bacteria in the blood.

Many of these oral bacteria were chemically altered by deimination; they were citrullinated. Citrullination can change the structure and function of proteins. Although citrullination can be a part of the normal function of tissues, high levels of citrullination have been linked to inflammation.

Citrullination can also create targets for ACPAs; when the normal, unconverted forms of the oral bacteria were incubated with ACPAs, the antibodies did not react, but when the citrullinated oral bacteria were exposed to ACPAs, there was a reaction. ACPAs appear to be bound to oral microbes in RA patients.

The findings have been reported in Science Translational Medicine.

The study noted that the immune response to oral microbes could be influencing RA flares, that oral microbes can trigger a specific antibody reaction in patients with both RA and gum disease, and that RA flares cause varying immune signatures, which could reflect different flare triggers.

It could be that gum disease repeatedly causes the immune system to respond, and as the immune system keeps reacting and repeatedly increasing inflammation, RA may eventually begin to emerge. More work will be needed, however, to fully understand whether gum disease is playing a causative role in the development of RA.

Source: Science Translational Medicine


Carmen Leitch

Microbiology

A variety of studies have shown that when the air is drier, viral particles can linger there longer. …

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A variety of studies have shown that when the air is drier, viral particles can linger there longer. These findings have now been confirmed in an analysis of particles of a virus that is very similar to the one that causes COVID-19, SARS-CoV-2. Although previous work has shown that relative humidity levels affect the length of time of a virus stays infectious in the air, this is the first to factor in the effect of saliva, which helps shield viral particles. The data can help explain why people tend to get more sick during winter, when humidity levels drop significantly indoors. It also stresses the importance of good ventilation systems and other mitigation efforts for preventing the spread of illness. The work has been reported in PNAS Nexus.

Dr. Mark Hernandez, S. J. Archuleta Professor of Civil and Environmental Engineering, and CU PhD graduate Marina Nieto-Caballero, now a postdoctoral researcher at Colorado State University, standing inside a bioaerosol chamber in the Environmental Engineering disinfection laboratory at the Sustainability, Energy and Environment Complex (SEEC). Credit Patrick Campbell/University of Colorado

This study used a mammalian coronavirus that is very similar to SARS-CoV-2. Particles containing this virus remained infectious for twice as long when air was drier. These particles are normally expelled with saliva, which acts like a protective shield, particularly when humidity is low.

Although civil engineers typically design and maintain buildings so their indoor relative humidity will stay between 40 and 60 percent, the reality is a bit different, and varies widely depending on the climate of the region. The researchers suspected that these humidity levels were influencing the spread of SARS-CoV-2.

To test that theory, the investigators engineered airborne particles containing virus, with and without saliva. These were then released into large, sealed chambers with relative humidity levels of 25, 40, and 60 percent.

The saliva protected the virus at every humidity level, and at 40 and 60 percent relative humidity, half of the airborne viral particles were still infectious one hour after release. Half of the airborne particles were still infectious two hours after release at 25 percent humidity; as the relative humidity dropped, the virus was still pathogenic for much longer.

“It shows this virus can hang around for quite a while, hours even. It’s longer than a class, longer than the time you’re in a restaurant, longer than the time you take to hang out in the cafe. An occupant may come in, spread coronavirus in the air, and leave. Depending on architectural factors, then someone else could walk into that space with potent doses still hanging around,” said senior study author Mark Hernandez, a Professor of Civil and Environmental Engineering at the University of Colorado at Boulder.

The virus is probably also contaminating air for longer than it takes typical ventilation systems to eliminate it. Thus, additional mitigation strategies like filtration could reduce transmission, suggested the study authors.

“I hope this paper has an engineering impact in our buildings, for example, in schools and hospitals, so that we can minimize the infectivity of these viruses in the air,” said lead study author Marina Nieto-Caballero, PhD.

Increasing indoor humidity levels could help reduce risk for people who live in naturally arid environments, but that can be inefficient and expensive, said Hernandez. We can use strategies that we already know about instead, like opening windows, using inexpensive air filters, and increasing ventilation rates to introduce more fresh air, Hernandez added.

Sources: University of Colorado at Boulder, PNAS Nexus


Carmen Leitch

Microbiology

Scientists have found that a gene that has been previously identified in many animals and their associated microbes …

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Scientists have found that a gene that has been previously identified in many animals and their associated microbes can enable resistance to antimicrobial drugs. The resistance gene encodes for an enzyme called EstT, which can deactivate antibiotic drugs known as macrolides. The enzyme can disrupt the chemical ring structure of these antibiotics through hydrolysis. When the ring is broken or opened with water, the antibiotic loses both its active shape, and its target affinity, explained study leader Dr. Tony Ruzzini PhD, an assistant professor at the Western College of Veterinary Medicine (WCVM) of the University of Saskatchewan. The findings have been reported in the Proceedings of the National Academy of Sciences.

Image credit: Pixabay

This gene can take macrolide antibiotics out of commission, and illnesses can no longer be treated effectively. Macrolides such as tylosin, tilmicosin and tildipirosin are often used to treat cattle with bovine respiratory disease or liver abscesses, and may also be used to treat other diseases in livestock and companion animals.

In this study, the researchers analyzed genes that were found within microbes that were living in watering bowls at a beef cattle feedlot in western Canada. The investigators isolated the microbes that were in the water, and compared the genes in the microbes to databases of antimicrobial resistance genes.

A bacterium called Sphingobacterium faecium WB1 was found to carry the EstT gene, which was contained within a cluster of three antibiotic resistance genes (ARGs). It was also near plasmids and retrotransposons, suggesting it can move easily from one microbe to another. EstT is commonly found in microbes in the human microbiome too.

“This gene, even though we found it in an environmental organism, it is also present in pathogens that are responsible for causing bovine respiratory disease,” noted Ruzzini.

“Our finding adds to the considerable database of ARGs, which can be crossmatched to a bacteria’s DNA to determine if the bacterium has the potential to be resistant to a particular antimicrobial,” said first study author Dr. Poonam Dhindwal PhD, a postdoctoral fellow at WCVM.

The researchers are continuing to study EstT to learn more about how it works.

“As [antimicrobial resistance] surveillance systems rely more on molecular tools for detection, our knowledge of this specific gene and its integration into those systems will help to better inform antimicrobial use,” said Ruzzini.

Sources: University of Saskatchewan, Proceedings of the National Academy of Sciences (PNAS)


Carmen Leitch

Microbiology

For many years, there was debate about whether chronic fatigue syndrome was a ‘real’ disorder. It took time, …

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For many years, there was debate about whether chronic fatigue syndrome was a ‘real’ disorder. It took time, but patients were eventually validated, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was shown to be a disease that can cause various symptoms including fatigue, pain, cognitive difficulties, sleep problems, gastrointestinal issues, and post-exertional malaise. The causes of ME/CFS are still unclear and there is no way to treat it. But the gut microbiome has been shown to play a crucial role in many aspects of human health and disease, and now scientists have shown that the gut microbiomes of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) differ from those of healthy individuals. Two studies reported in Cell Host & Microbe have outlined these differences, showing that they might be used to diagnose ME/CFS. The gut microbiome may also present a treatment opportunity.

Image credit: Pixabay

In one of the studies, researchers assessed the gut bacteria of 106 people with ME/CFS and 91 healthy controls by analyzing stool samples. This research showed that the diversity of species, quantity of microbes, metabolic interactions, and relationships among the gut microbes were different from controls.

ME/CFS patients had unusually low levels of several types of bacteria, including Eubacterium rectale and Faecalibacterium prausnitzii, which generate the short-chain fatty acid butyrate. Previous research has shown that butyrate, a microbial metabolic byproduct, plays a crucial role in gut health maintenance. Butyrate provides a source of energy for cells lining the gut, aids in protecting the cells from disease, and supports the immune system in the gut.

Additional work showed that the reduction of certain bacteria levels was linked to decreases in butyrate production. With fewer butyrate-producing bacteria present, there were other species to fill the void. ME/CFS patients had higher levels of nine microbes, including two that have been linked to autoimmune disorders and inflammatory bowel disease – Enterocloster bolteae and Ruminococcus gnavus.

Symptoms of fatigue were found to increase as levels of F. prausnitzii decreased in ME/CFS patients, which suggests that disease severity may depend on gut microbe levels. People with ME/CFS also had low levels of a microbe that generates acetate.

Biochemical processes in the gut, which are influenced by relationships among gut microbes, were also notably different from controls; the bacterial network seems to be totally altered in ME/CFS patients.

The second report analyzed differences in the microbiomes of ME/CFS patients in different stages of disease. Health data, blood, and stool samples were analyzed from 149 ME/CFS patients; 74 of them had been diagnosed within the previous four years and were classified as short-term, while 75 had been diagnosed over a decade prior and were long-term. There were 74 healthy controls included in this work.

Those who were short-term had less diversity in their microbiomes and significantly lower levels of species that generate butyrate. Long-term patients had more stable microbiomes that were more similar to healthy controls, even while these individuals had more severe symptoms and worse metabolic disturbances. In all ME/CFS patients, tryptophan metabolism was decreased.

This work has shown that there could be biomarkers for ME/CFS in the microbiome, which could also help classify the disease and may lead to treatments, though a lot more research will be needed before those tests and treatments are realized.

Sources: National Institutes of Health, Cheng Guo et al Cell Host & Microbe 2023, Ruoyun Xiong et al Cell Host & Microbe 2023


Carmen Leitch

Microbiology

Even after decades of research, the cause of the most common form of dementia, Alzheimer’s disease, is unclear. …

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Even after decades of research, the cause of the most common form of dementia, Alzheimer’s disease, is unclear. Evidence that pointed to plaques and tangles of disordered proteins called amyloid beta and tau has been called into question since therapeutics that aim at the protein clumps have not been particularly effective at relieving disease. In recent years, scientists have also found evidence that viral infections may be to blame for some serious long-term diseases; multiple sclerosis, for example, seems to only develop in people who have been infected with Epstein-Barr virus (EBV). The pandemic coronavirus SARS-CoV-2 also appears to have neurological impacts in some people.

Influenza B virus particles, colorized blue, isolated from a patient sample and then propagated in cell culture. Both influenza A and B can cause seasonal flu; however, unlike influenza A virus, which can also infect animals, influenza B only infects humans. Microscopy by John Gallagher and Audray Harris, NIAID Laboratory of Infectious Diseases. Credit: NIAID

Researchers have now used the power of biobanks that contain health data from hundreds of thousands of people to look for links between viral infections like influenza and EBV and neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), generalized dementia, and Parkinson’s disease. Data from FinnGen on over 300,000 people was used to look for associations that were then assessed in the nearly half a million people in the UK Biobank for confirmation. An additional cohort of almost 100,000 people who had not had any neurodegenerative disorder was used as a control group. COVID-19 hospitalizations were not included in this study. The findings have been reported in Neuron.

The research showed that there is a connection between viral infections and neurodegeneration, which is particularly significant for viruses that are able to cross the blood brain barrier and infect the central nervous system, perhaps unsurprisingly. The study authors suggested that these so-called neurotropic viruses may be causing neurodegeneration because of neuroinflammation.

A first pass of the data suggested there were 45 significant associations between viral infections and neurodegenerative disease. After querying the UK Biobank, the researchers refined it to 22 associations.

The top candidate was generalized dementia, which was linked to infections with six different viruses: all influenza, flu and pneumonia, viral pneumonia, viral encephalitis, viral warts, and other viral diseases seem to raise the risk of generalized dementia. The research also showed that anyone who had viral encephalitis was 20 times more likely or more to receive an Alzheimer’s diagnosis compared to people who have not had viral encephalitis.

Severe flu was connected to a greater likelihood of different types of neurodegeneration. Influenza and pneumonia exposures were also linked to an increased risk of all neurodegenerative disorders except multiple sclerosis.

Senior study author Michael Nalls, Ph.D., the NIH Center for Alzheimer’s Related Dementias (CARD) Advanced Analytics Expert Group leader, also noted that the viral infections that are being considered in this study were quite severe and led to hospitalizations; they were not mild cases of the common cold.

“Nevertheless, the fact that commonly used vaccines reduce the risk or severity of many of the viral illnesses observed in this study raises the possibility that the risks of neurodegenerative disorders might also be mitigated,” said Nalls.

“Our results support the idea that viral infections and related inflammation in the nervous system may be common and possibly avoidable risk factors for these types of disorders,” added study co-author Andrew B. Singleton, Ph.D., the director of CARD.

Sources: National Institutes of Health, Neuron


Carmen Leitch