Tag Archives: Chronic Disease

Study expands the knowledge about gut viral diversity in healthy infants

Viruses are usually associated with illness. But our bodies are full of both bacteria and viruses that constantly proliferate and interact with each other in our gastrointestinal tract. While we have known for decades that gut bacteria in young children are vital to protect them from chronic diseases later on in life, our knowledge about the many viruses found there is minimal.

A few years back, this gave University of Copenhagen professor Dennis Sandris Nielsen the idea to delve more deeply into this question. As a result, a team of researchers from COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) and the Department of Food Science at UCPH, among others, spent five years studying and mapping the diaper contents of 647 healthy Danish one-year-olds.

“We found an exceptional number of unknown viruses in the feces of these babies. Not just thousands of new virus species – but to our surprise, the viruses represented more than 200 families of yet to be described viruses. This means that, from early on in life, healthy children are tumbling about with an extreme diversity of gut viruses, which probably have a major impact on whether they develop various diseases later on in life,” says Professor Dennis Sandris Nielsen of the Department of Food Science, senior author of the research paper about the study, now published in Nature Microbiology.

The researchers found and mapped a total of 10,000 viral species in the children’s feces – a number ten times larger than the number of bacterial species in the same children. These viral species are distributed across 248 different viral families, of which only 16 were previously known. The researchers named the remaining 232 unknown viral families after the children whose diapers made the study possible. As a result, new viral families include names like Sylvesterviridae, Rigmorviridae and Tristanviridae.

Bacterial viruses are our allies

This is the first time that such a systematic an overview of gut viral diversity has been compiled. It provides an entirely new basis for discovering the importance of viruses for our microbiome and immune system development. Our hypothesis is that, because the immune system has not yet learned to separate the wheat from the chaff at the age of one, an extraordinarily high species richness of gut viruses emerges, and is likely needed to protect against chronic diseases like asthma and diabetes later on in life.”

Shiraz Shah, first author and senior researcher at COPSAC

Ninety percent of the viruses found by the researchers are bacterial viruses – known as bacteriophages. These viruses have bacteria as their hosts and do not attack the children’s own cells, meaning that they do not cause disease. The hypothesis is that bacteriophages primarily serve as allies:

“We work from the assumption that bacteriophages are largely responsible for shaping bacterial communities and their function in our intestinal system. Some bacteriophages can provide their host bacterium with properties that make it more competitive by integrating its own genome into the genome of the bacterium. When this occurs, a bacteriophage can then increase a bacterium’s ability to absorb e.g. various carbohydrates, thereby allowing the bacterium to metabolize more things,” explains Dennis Sandris Nielsen, who continues:

“It also seems like bacteriophages help keep the gut microbiome balanced by keeping individual bacterial populations in check, which ensures that there are not too many of a single bacterial species in the ecosystem. It’s a bit like lion and gazelle populations on the savannah.”

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Shiraz Shah adds:

“Previously, the research community mostly focused on the role of bacteria in relation to health and disease. But viruses are the third leg of the stool and we need to learn more about them. Viruses, bacteria and the immune system most likely interact and affect each other in some type of balance. Any imbalance in this relationship most likely increases the risk of chronic disease.”

The remaining ten percent of viruses found in the children are eukaryotic – that is, they use human cells as hosts. These can be both friends and foes for us:

“It is thought-provoking that all children run around with 10-20 of these virus types that infect human cells. So, there is a constant viral infection taking place, which apparently doesn’t make them sick. We just know very little about what’s really at play. My guess is that they’re important for training our immune system to recognise infections later. But it may also be that they are a risk factor for diseases that we have yet to discover,” says Dennis Sandris Nielsen.

Could play an important role in inflammatory diseases

The researchers have yet to discover where the many viruses in the one-year-olds come from. Their best answer thus far is the environment:

“Our gut is sterile until we are born. During birth, we are exposed to bacteria from the mother and environment. It is likely that some of the first viruses come along with these initial bacteria, while many others are introduced later via dirty fingers, pets, dirt that kids put in their mouths and other things in the environment,” says Dennis Sandris Nielsen.

As Shiraz Shah points out, the entire field of research speaks to a huge global health problem:

“A lot of research suggests that the majority of chronic diseases that we’re familiar with – from arthritis to depression – have an inflammatory component. That is, the immune system is not working as it ought to – which might be because it wasn’t trained properly. So, if we learn more about the role that bacteria and viruses play in a well-trained immune system, it can hopefully lead us to being able to avoid many of the chronic diseases that afflict so many people today.”

The research groups have begun investigating the role of gut viruses in relation to a number of different diseases that occur in childhood, such as asthma and ADHD.

Journal reference:

Shah, S. A., et al. (2023). Expanding known viral diversity in the healthy infant gut. Nature Microbiology. doi.org/10.1038/s41564-023-01345-7.

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

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

Hundreds of research studies have now investigated long COVID, in which symptoms of COVID-19 and other health issues …

Hundreds of research studies have now investigated long COVID, in which symptoms of COVID-19 and other health issues linger for months after the acute phase of infection has passed. Long COVID can occur in people who have had any type of case of COVID-19, from the mild to the severe. Researchers have been categorizing various symptoms of long COVID, and have proposed that there are subtypes of the disease. Scientists have also been following long COVID cases to determine how long symptoms might last.

Colorized scanning electron micrograph of a cell (green) infected with the Omicron strain of SARS-CoV-2 virus particles (pink), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

In a new report published in the Journal of the Royal Society of Medicine, scientists have shown that organ damage continued to occur in 59 percent of long COVID patients twelve months after their symptoms started. This was true even for some people who had not experienced severe COVID-19.

This research included 536 long COVID patients, 13 percent of whom had been hospitalized when they were diagnosed with COVID-19. Patients who had reported poor quality of life, extreme breathlessness, and cognitive dysfunction were a focus of this study.

Out of 536 study participants, 331 (62 percent) had persistent organ dysfunction six months after they’d been initially diagnosed. There was a followup with the study volunteers six months later, in which they received an organ MRI scan. This revealed that 29 percent of long COVID patients were having trouble with multiple organs, such as reduced function and other symptoms specific to the organ. At the one-year followup, there was impairment in a single organ in 59 percent of the study participants.

Symptoms of breathlessness began to go away between six and twelve months, but only for some patients; the individuals reporting breathlessness at six months was 38 percent, and it dropped to 30 percent at one year; cognitive dysfunction decreased from affecting 48 to 38 percent of particpants; quality of life disruptions were experienced by 57 percent, then 45 percent of patients.

“Several studies confirm persistence of symptoms in individuals with long COVID up to one year. We now add that three in five people with long COVID have impairment in at least one organ, and one in four have impairment in two or more organs, in some cases without symptoms,” said study co-author Professor Amitava Banerjee of the UCL Institute of Health.

More research will still be needed to understand the mechanisms underlying the development of long COVID.

Sources: Eurekalert! via SAGE Publications, Journal of the Royal Society of Medicine

Carmen Leitch

We now know that even mild cases of COVID-19 can lead to long COVID, in which symptoms linger …

We now know that even mild cases of COVID-19 can lead to long COVID, in which symptoms linger for weeks, months, or longer, detracting from people’s ability to lead a normal life. Scientists are starting to characterize long COVID, which will help us learn more about how it arises and find ways to treat the disorder. A major effort by the National Institutes of Health, Researching COVID to Enhance Recovery (RECOVER) is now ongoing (and still recruiting); it has used electronic health records to look for symptom patterns in about 35,000 Americans who were infected with SARS-CoV-2 (the virus that causes COVID-19) and went on to develop symptoms that are known as long COVID.

Novel Coronavirus SARS-CoV-2  Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-CoV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

It’s not unusual for viral infections to cause lingering symptoms in people, and they can be hard to define and treat. In the case of COVID-19, these symptoms have been called post-acute SARS-CoV-2 infection (PASC), or more commonly, long COVID. It’s been estimated that as many as 40 percent of Americans have had long COVID symptoms at some point.

There are many physiological issues that have been linked to long COVID, including loss of taste or smell, fatigue, headache, dizziness, depression, anxiety, cough, chest pain, joint pain, muscle pain, or gastrointestinal distress, among other symptoms.

A new RECOVER study published in Nature Medicine has outlined four major subtypes of long COVID, which are characterized by different symptom clusters.

  • One subtype involves heart, circulation, and kidney dysfunction, and a high proportion of these patients were infected in the initial months of the US pandemic. This group accounted for about 34 percent of long COVID patients. The sex ratio is roughly one-to-one in this group, and patients were older, with a median age of 65. About 61 percent had been hospitalized for COVID.
  • A second subtype is related to anxiety, sleep disorders, headache, chest pain, and respiratory problems; about two-thirds of these individuals were women. Around 33 percent of long COVID patients were in this category. Their median age was 51; and fewer of them, about 31 percent, had been hospitalized for COVID. The people in this group tended to get COVID between November 2020 and November 2021. Many of them had underlying respiratory conditions like asthma or chronic obstructive pulmondary disorder (COPD).
  • The final two subtypes did not include as many patients. About 23 percent of patients were in the third group, with musculoskeletal and nervous system issues.
  • The final subtype, which included ten percent of patients, experienced digestive and respiratory symptoms.

“RECOVER is aiming to rapidly elucidate what is happening in long COVID. Looking at how cases cluster can profoundly impact the prognosis and care of patients,” said co-senior study author Dr. Rainu Kaushal, chair of the Department of Population Health Sciences at Weill Cornell Medicine, among other appointments.

“This sex difference in long-COVID risk is consistent with prior research, but so far very few studies have even tried to uncover the mechanisms underlying it,” noted study leader Dr. Fei Wang, an associate professor of population health sciences at Cornell.

Now the investigators want to follow up on these findings to look for risk factors that predispose people to certain subtypes of long COVID, and identify existing medications that might be repurposed to use as long COVID treatments.

Another part of the RECOVER initiative has also used machine learning to analyze long COVID trends. Reporting in eBioMedicine, this work indicated that there are links between underlying conditions such as diabetes or hypertension and the risk of long COVID.

Sources: Cornell University, Nature Medicine

Carmen Leitch

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and …

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and Prevention (CDC) has estimated that the number could be as high as 476,000. Lyme disease is also becoming more common in other countries, with an estimated 200,000 cases in Western Europe every year. Ixodes tick bites transmit the bacteria that cause Lyme disease; these pathogens are varieties of Borrelia bacteria, including Borrelia burgdorferi in the US and B. afzelii and B. garinii in Europe. The disease causes rash, fever, joint pain, and can lead to nervous system and heart complications.

A digitally colorized SEM image at high magnification, depicting three Borrelia burgdorferi bacteria, derived from a pure culture. / Credit: CDC/ Claudia Molins / Photo Credit: Jamice Haney Carr

Now scientists may have learned how Borrelia bacteria migrate from the site of a bite to an infected person’s bloodstream. For this work, researchers created a specialized 3D tissue model that was meant to mimic a human blood vessel, the skin around it, and the tick bite. High-resolution optical imaging was used to monitor the bacteria. This showed that  B. burgdorferi basically uses trial and error to find an opening in spaces called junctions, which line blood vessels and can be found near the sites of bites. Once the pathogenic microbes break through, they can move into the bloodstream and on to other tissues and organs. The findings have been reported in Advanced Science.

If Borrelia could not find a junction right away, they kept searching until they found one, said senior study author Peter Searson, a professor at the Whiting School of Engineering of Johns Hopkins University. “The bacteria spend an hour or two using this behavior to find their way into the blood vessels, but once there, they are in circulation in a matter of seconds.”

Understanding how these bacterial pathogens spread could help scientists develop treatments for Lyme disease, which can cause symptoms that last for months or even years. It may be possible to prevent the pathogens from moving beyond the site of the initial bite.

The researchers have experience developing vascular models with tissue engineering, and they applied what they knew to make a dermal tissue model.

“We also believe that the kind of human tissue-engineered model we created can be broadly applied to visualize the details of dynamic processes associated with other vector-borne diseases and not just Lyme disease,” Searson added.

Sources: CDC, WHO, Johns Hopkins University, Advanced Science

Carmen Leitch

After only a few months of the COVID-19 pandemic, scientists and clinicians knew that the virus could cause …

After only a few months of the COVID-19 pandemic, scientists and clinicians knew that the virus could cause myriad health problems in various organs throughout the body. While a SARS-CoV-2 infection begins as in the nose, airways, and lungs, it can go on to disrupt the function of blood vessels, interfere with senses of taste and smell, and cause gastrointestinal distress, for some examples. There can also be a host of long-term effects that are so common in patients who have recovered from an initial COVID-19 infection, there is a term form it – long COVID, or post acute coronavirus syndrome (discussed in the video below).

Colorized scanning electron micrograph of chronically infected and partially lysed cells (green) infected with a variant strain of SARS-CoV-2 virus particles (blue), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

While people can develop immunity to SARS-CoV-2 from an infection, a vaccine shot, or a combination of those things, the virus has continued to mutate, which it is still doing, and it can infect people multiple times. Scientists have now found that repeat SARS-CoV-2 infections significantly increases the likelihood of other health problems, which can affect the brain, heart, lungs, gastrointestinal system, mucoskeletal system, and mortality. Repeat infections also increase the risk of kidney disease, mental health issues, and diabetes. The findings have been reported in Nature Medicine.

“Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase,” said senior study author Ziyad Al-Aly, MD, a clinical epidemiologist at the School of Medicine.

The risks appear to increase with every infection. So if you have already had COVID-19, two or even three times, it’s still best to avoid getting it again, said Al-Aly, who added that people who have been vaccinated, been sick with COVID-19, or both, should not feel invincible. Prevention continues to be very important.

If you can be in well-ventilated areas, try to do so, and take precautions. Anyone who is eligible should wear a mask, get boosted, and get a flu shot, said Al-Aly. This is particularly important as the winter season arrives, and new variants keep emerging.

The study authors assessed about 5.8 million medical records from a U.S. Department of Veterans Affairs database, with multiple races, ages, and sexes represented. Of those, about 5.3 million did not get COVID-19 between March 2020 and April 2022, so they served as controls. Another 443,000 people did get one COVID-19 infection during that time, while almost 41,000 had two documented infections, or more. Most of them had been sick two or three times, while a small number of people had four infections (no one had five documented cases, according to the database).

Taking several factors into account, including vaccination status and the variant causing the infection, the researchers found that people who had COVID-19 reinfections were twice as likely to die and three times as likely to be hospitalized with a subsequent COVID-19 case compared to people who had not been reinfected. Repeat infections also made people 3.5 times more likely to develop problems in their lungs, three times as likely to have heart problems, and 1.6 times more likely to have brain disorders compared to people who only got COVID-19 once.

One thing that is unclear is how researchers might be able to account for very mild or asymptomatic cases of COVID-19 that might not have been diagnosed or documented. Unfortunately, a lack of routine testing in the United States has made data on those mild cases impossible to ascertain.

Sources: Washington University in St. Louis, Nature Medicine

Carmen Leitch

Scientists have developed a gel that can block the receptor for a molecule called succinate, which is a …

Scientists have developed a gel that can block the receptor for a molecule called succinate, which is a normal byproduct of metabolism. By blocking its receptor, the gel can lower inflammation levels in the mouth, and alter the community of oral bacteria living there. The work, which used a mouse model and human cells in culture, is the first step on the path to a simple, at-home treatment for gum disease. The work has been published in Cell Reports.

Image credit: Pixabay

Periodontitis, also known as periodontal or gum disease, is one of the most common inflammatory disorders, and is thought to affect almost half of all people older than 30. There are three hallmarks of gum disease: inflammation, an imbalance or dysbiosis in the oral microbiome, and degradation of the support structures and bones underlying teeth. When gum disease is left untreated, it can cause gums to become painful and bleed. Gum disease patients might have trouble chewing, and may eventually start to lose teeth. Serious gum problems can also interfere with other aspects of health.

Right now, there is not a gum disease treatment that can reduce inflammation, while simultaneously limiting disruption to the oral microbiome and preventing the loss of bone, noted co-first study author Yuqi Guo, an associate research scientist at NYU Dentistry. “There is an urgent public health need for more targeted and effective treatments for this common disease.”

Previous research has indicated that a molecule that is generated during cellular metabolism, called succinate, is associated with gum disease. Higher succinate levels also correspond to higher levels of inflammation. Abnormally high succinate levels were found in human dental plaque. This team has also shown that excess succinate activates its receptor and triggers bone loss. Thus, succinate seemed like a good target to aim for when developing treatments for excessive inflammation, and potentially, gum disease or bone loss.

The researchers engineered mice that lacked the succinate receptor. When gum disease was modeled in these succinate receptor-depleted mice, there was less dysbiosis in their oral microbiomes, and lower levels of inflammation compared to normal mice with gum disease. When mice were exposed directly to succinate, gum disease got worse in normal mice, while the mice without succinate receptors did not experience inflammation, dysbiosis, or bone loss.

Now that the researchers had evidence that high succinate levels can lead to gum disease, and blocking the receptor can relieve it, they formulated a gel containing a succinate receptor-blocking compound.

In a cell culture model, the compound lowered inflammation and other biochemical mechanisms leading to bone loss. When a mouse model of gum disease was treated with the gel, the animals had less inflammation and bone loss compared to mice that did not get the treatment, and within only a few days. There was also a shift in the oral microbiome of the mice. Bacteria called Bacteroidetes, which are dominant during gum disease, were reduced after gel treatment.

However, the investigators determined that the gel was not acting as an antibiotic and was not influencing bacterial growth directly. “This suggests that the gel changes the community of bacteria through regulating inflammation,” suggested co-senior study author Deepak Saxena, a professor at NYU Dentistry.

The researchers want to eventually create gels or oral strips that can be used at home by gum disease patients or those at risk, and a formulation that releases more slowly that can be applied to patches of gum disease.

Sources: New York University, Cell Reports


Carmen Leitch