Category: 8. Health

A new study uncovers how gut bacteria may switch from digesting plant fibers to consuming protective mucus when fiber is scarce, fueling inflammation even in people without gut disease.

Study: Gut microbiome genes involved in plant and mucin breakdown correlate with diet and gastrointestinal inflammation in healthy US adults. Image credit: Tatjana Baibakova/Shutterstock.com

In a recent study published in The Journal of Nutrition, researchers investigated the impact of fiber scarcity on the gut’s “carbohydrate-active enzymes” (CAZymes) and their subsequent role in gastrointestinal inflammation amongst healthy United States (US) adults. The study leveraged data from 330 participants and found that a higher ratio of mucin-degrading to plant-degrading enzymes, a novel metric they termed Muc2Plant, was strongly associated with increased gastrointestinal inflammation.

Study findings highlight that the Muc2Plant ratio was positively correlated with fecal inflammation biomarkers (e.g., calprotectin [p=0.001] and neopterin [p<0.001]), suggesting that imbalances in microbial digestive function (due to low fiber utilization and greater reliance on mucin degradation) can promote a pro-inflammatory state even in healthy individuals, thereby providing insight into potential targets for intervention.

Background

While organisms like humans were historically believed to be able to digest much of the food they consume, more recent research has demonstrated that a large portion of the food we consume (e.g., complex carbohydrates) is broken down by the vast enzymatic machinery of the symbiotic gut microbiome.

Gut microbiotas are known to produce thousands of carbohydrate-active enzymes (CAZymes) that process insoluble plant fibers, releasing beneficial short-chain fatty acids (SCFAs) with validated inflammation-mitigating effects. Unfortunately, recent studies have observed that in the absence of sufficient dietary fiber, some gut microbes can switch to alternative food sources, primarily the mucus layer (made of glycoproteins called mucins) that lines and protects the intestines.

This degradation of the protective mucin barrier is a hallmark of dysbiosis and has been previously linked to inflammatory bowel disease (IBD). Although the harmful effects of low fiber on gut health are well documented, few studies have directly examined how fiber influences both the gut microbiome’s enzymatic activity (whether microbes choose plant material or mucin as fuel) and gastrointestinal inflammation simultaneously.

About the study

The present study aims to systematically investigate the relationship between dietary fiber intake, the gut microbiome’s enzymatic capacity, and subclinical gut inflammation biomarkers in a cohort of healthy American adults. The cross-sectional study leveraged data from the United States Department of Agriculture (USDA) Nutritional Phenotyping Study (participant n = 330 individuals).

Data of interest included participants’ socioeconomic demographic information (for statistical model standardization), detailed dietary information (using 24-hour recalls [ASA24] and food frequency questionnaires [FFQ]), and fecal samples (for microbiome characterization, enzymatic estimation, and inflammation biomarker assessment).

Key study analyses included shotgun metagenomic sequencing to identify all the microbial genes present in the gut, allowing for a detailed profiling of individual-specific CAZyme repertoires. It also included fecal biomarkers to measure markers of gastrointestinal inflammation, including fecal calprotectin, neopterin, and myeloperoxidase (MPO).

Study findings were used to develop a novel metric (“Muc2Plant”), representing the ratio between the abundance of mucin-degrading CAZyme genes and plant-degrading CAZyme genes. Analyses revealed that a higher Muc2Plant ratio indicates a microbiome better equipped to digest the host’s mucus lining relative to dietary fiber, suggesting reduced fiber utilization and heightened inflammation risk.

Study findings

The present study demonstrates a measurable correlation between dietary fiber intake and CAZyme gene recruitment. Habitual intake of total and soluble fiber was positively correlated with a greater abundance and diversity of plant-degrading CAZymes (adjusted R² = 0.015, p = 0.010 for abundance). A lower fecal pH, indicating robust fiber fermentation, was similarly associated with a higher capacity for fiber digestion (adjusted R² = 0.036, p < 0.001).

The study also validated the utility of the novel Muc2Plant ratio. Higher ratios, indicative of enhanced mucin degradation, significantly and positively correlated with markers of gut inflammation, even in this phenotypically healthy cohort.

Specifically, a higher Muc2Plant ratio was observed to be associated with higher levels of fecal calprotectin (adjusted R² = 0.038, p = 0.001), a well-established marker of neutrophil infiltration in the gut, and higher levels of fecal neopterin (adjusted R² = 0.071, p < 0.001), a marker of macrophage-driven inflammation.

At the same time, plant-degrading CAZyme diversity and abundance were negatively associated with fecal myeloperoxidase but positively associated with fecal neopterin, highlighting that different immune pathways may be involved.

Surprisingly, the study found no link between dietary fiber intake and the Muc2Plant ratio. However, machine learning models identified that a higher intake of white potatoes significantly predicted a lower Muc2Plant ratio, suggesting that certain types of dietary starch may help foster a healthier microbial balance.

Conclusions

The present study did not find a direct relationship between dietary fiber intake and inflammation, but did highlight complex associations between dietary fiber intake, microbial enzymatic capacity, and inflammation biomarkers. It provides evidence that the functional capacity of the gut microbiome, specifically its balance of plant-digesting versus mucin-digesting enzymes, is a crucial factor in maintaining gut health.

The study also introduces and validates the novel Muc2Plant ratio metric, demonstrating the tool’s robust association with subclinical gastrointestinal inflammation, even without overt disease. It emphasizes that these findings are correlative and not causal.

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The World Health Organization and partners will raise global awareness during the 80^th United Nations General Assembly (UNGA) on progress to address a range of critical issues impacting people’s health worldwide, and urgent work that needs to be scaled up.

These will include protecting people from noncommunicable diseases (NCDs) like cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases; advocating for mental health; addressing the common risks caused by tobacco, unhealthy diet, alcohol, physical inactivity and also climate change; and finding solutions to raise resources to finance national health systems. Promoting peace as the best medicine to protect health and end conflicts in various parts of the world will also feature prominently during UNGA.

On 25 September, the Fourth UNHA High-level Meeting on NCDs and Mental health will be held, providing a status check on efforts to protect people from the world’s leading killers.

Combined, the four major  NCDs account for 74% of all deaths globally. The WHO Director-General, Dr Tedros Adhanom Ghebreyesus, is expected to address the opening of this event, joined by leadership of the United Nations, Member States and other key partners.

In addition, strategic events held on 24 September, in collaboration with partners, including the Bloomberg Philanthropies Global Forum, will focus on how pro-health taxes on harmful products such as tobacco can protect people’s health and raise needed resources for national health services. The challenge of the global obesity epidemic will also be a subject of major attention. In addition, WHO will release the Global Hypertension Report during the Assembly, warning that uncontrolled high blood pressure remains one of the world’s leading causes of premature death.

This year’s General Assembly takes place at a critical time for the multilateral system as it adapts to a range of new realities. WHO has been working closely with fellow UN agencies, through the UN80 Initiative, to improve efficiencies in its operations while remaining committed to deliver on its mission of advancing health for all.

WHO and partners will also be advocating for action to reduce the threats to health that people face worldwide from the impacts of conflicts, such as those in  Gaza, Sudan and Ukraine, climate change and diseases such as polio.

For real time updates on WHO and global health activities during UNGA, follow WHO and the Director-General’s social media accounts:

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As the effectiveness of antibiotics meant to fight the deadly superbug Clostridioides difficile, or C. diff, wanes, a research team at the University of Houston is seeing positive results of a new antibiotic on the scene — ibezapolstat — which is proving successful in fighting these infectious bacteria in clinical trials.

C. diff is the nation’s leading cause of death from gastroenteritis causing an estimated 453,000 infections yearly and 29,300 deaths. It causes gastrointestinal illness ranging from diarrhea and abdominal pain to toxic megacolon, sepsis and death.

Until now the frontline treatments for C. diff have been the antibiotics vancomycin, with a sustained clinical cure of 42% to 71%, and fidaxomicin at 67%.

And yet, a superbug would not be so deadly if it was not able to outlive the very medicines meant to destroy it.

“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. difficile infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. New antibiotics are urgently needed.” said Kevin Garey, Robert L. Boblitt Endowed Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author on recent clinical trial results with ibezapolstat published in Lancet Microbe.

C. diff infections often return when the natural balance in the gut stays disrupted — good bacteria like Bacillota, Bacteroidota, and Actinomycetota are reduced, while harmful types like Pseudomonadota increase. These changes can weaken the gut’s defenses, causing a loss of the kind of bacteria that helps break down bile acids. When that happens, harmful bacteria can easily take over.

“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence” said study lead author Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at UH.

Enter ibezapolstat

Ibezapolstat has a way of working that kills harmful C. difficile bacteria without harming the good bacteria in the gut that protect against C. diff infections.

“A randomized, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” reports Garey.

“Ibezapolstat was found to be safe, well tolerated, and was associated with the preservation of key health-promoting bacteria responsible for bile acid homoeostasis, a key component in preventing recurrent C. difficile infection.”

Eubank added, “This helps confirm the important anti-C diff recurrence properties of Ibezapolstat.”

Ibezapolstat is being developed by Acurx Pharmaceuticals progressing towards phase III clinical trials. The study was conducted at 15 centers, primarily outpatient clinics and hospitals in the United States. Participants were aged 18–90 years, with diarrhea and a confirmed diagnosis of mild or moderate C difficile infection.

“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.

Reference: Eubank TA, Jo J, Alam MJ, et al. Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study. Lancet Microbe. 2025;6(8):101126. doi: 10.1016/j.lanmic.2025.101126

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On Thanksgiving Day 1998, a geneticist called Donavon Decker and told him the lab had identified the gene that was causing his and his sisters’ muscles to slowly deteriorate. By the way, the geneticist added, this might be a good candidate for gene therapy.

Decker called back every month until April, when the researcher finally put him in touch with neurologist Jerry Mendell. Mendell said Decker could be of service — but that he couldn’t help Decker. 

Gene therapy was still new and risky. No muscular dystrophy patient had ever received one. To assure safety, Mendell would only inject a tiny foot muscle. Decker wouldn’t benefit. He could be harmed and might be rendered ineligible for future gene therapies. But if it worked, it could advance the field, including for his four sisters with the disease.

“He put his foot out,” Mendell recalled, “and said ‘go for it.’”

Decker died Monday at age 62. There are today still no treatments for his condition, known as limb-girdle muscular dystrophy (LGMD). But Decker’s study paved the way for gene therapy’s resurgence over the past decade, including approval of the first gene therapy for spinal muscular atrophy and Duchenne, the most well-known and fatal form of muscular dystrophy.

That trial “really set the stage for everything that came afterwards,” said Sharon Hesterlee, a longtime friend of Decker as well as interim head of the Muscular Dystrophy Association (MDA), which sponsored the 1999 study. 

He died of complications from an elevator accident, exacerbated by the toll the disease had taken on his lungs.  

Those in the muscular dystrophy community remembered a fearless and indefatigable advocate who set an example and served as a resource for other parents and patients. “I could cry just talking about him,” said Kelly Brazzo, whose daughter has LGMD. “He moved the gene therapy field forward without ever seeing a benefit himself, just a heroic and selfless act.” 

The excitement over Decker’s study faded fast. Three days after his injection, he and Mendell appeared on the Jerry Lewis MDA Telethon, where they both spoke about the promise of an imminent cure. Less than two weeks later, 18-year-old Jesse Gelsinger died in a misstep-ridden trial at the University of Pennsylvania. The field, including the LGMD study, shut down overnight.  

Decker, though, remained a force in the community. In 2001, he testified before Congress to push for the MD Care Act, a bill that dramatically expanded federal investment into muscular dystrophy, and served on the research coordinating committee the law created.

Mendell, who in 2004 became director of the gene therapy center at Nationwide Children’s Hospital, kept working too, relying in part on data from Decker’s foot. It had been one of the first studies to try to ferry genes into the body with a new, potentially safer group of viruses, called AAVs, than the one Gelsinger received. 

Although the results weren’t a home run — the dose was infinitesimal — it showed they could safely deliver genes into muscle, Mendell said. Although he never published the data, he said he used it when submitting applications to the Food and Drug Administration.

In 2013, as the gene therapy field began its modern resurgence, Mendell was ready to start a new trial for Decker’s subtype, called LGMD 2D, this time infusing a full leg, through the blood stream. There are dozens of LGMD subtypes, each tied to a different gene. LGMD 2D, while ultra-rare, had been chosen because it was more common than others, and the gene could fit snugly into viruses.

Decker volunteered again. But a blood test showed he still had antibodies from the 1999 trial. They would block the gene therapy, which used the same category of virus. “So he asked me if I knew anyone else that would do [it],” Decker recalled at a speech at the MDA’s conference earlier this year, when he was given an MDA Legacy Award for Community Impact in Research. 

His sister June Burney stepped forward, becoming the first muscular dystrophy patient to receive gene therapy through the new system. She saw some benefit, Decker recalled, but then regressed.

Mendell moved to dose patients systemically, the approach that would eventually lead to Elevidys, the gene therapy for Duchenne. But that’s where LGMD efforts began sputtering. 

After promising early results in LGMD 2E, Sarepta Therapeutics bought out a startup spun out of Nationwide to develop one-time treatments for five different subtypes. But it did not move most of those programs forward, including the 2D treatment, for years, spending most of its resources on Duchenne.

The delays frustrated Decker. Fellow advocates described him as a kind, soft-spoken man, with ample time, support, and wisdom ready, including for those facing a new diagnosis. And he had a humorous streak: He often recounted how, at the end of his hospital stay for Mendell’s trial, he yelped in pain when Mendell poked the site of the injection — the doctor jumped back, terrified the gene therapy had gone horribly awry, only to look up to see Decker laughing. But he could be a fierce advocate when he felt LGMD patients were being left behind.

LGMD is often described as a less common and less severe form of muscular dystrophy. But he saw the toll the disease could take. In the years since the 1999 trial, he became fully reliant on his wheelchair and had to leave his job as an air traffic control specialist. He lost three sisters to the disease, which slowly sapped strength from their lungs. “They don’t understand the urgency,” he said in a documentary, “In Search of Strength,” about his life that came out this year.

“Sometimes I feel overwhelmed when I see nothing happening, and I can see how some companies are not working on the research like they say they do,” he said. “That makes me angry at times and sometimes it gets the best of me, but it also makes me a strong advocate.”

He kept testifying, explaining to the Food and Drug Administration the abilities the disease had taken from him and advocating for the agency for flexibility in ultra-rare diseases.

And he encouraged other advocates to not leave their full faith in companies. Joe Dion remembered meeting him in 2023, when Sarepta was working on a gene therapy for LGMD 2C, a condition both his children were facing. 

Decker encouraged Dion to remain skeptical, advice that led him to fund an alternative gene therapy effort. Both of his children have been dosed this year, while Sarepta, facing financial challenges and the death of a patient in another LGMD trial, pulled away from the disease altogether. 

“If that wasn’t for him” his kids would never have been treated, said Dion. He credits the treatment with giving his 12-year-old son, Peter, who had been declining, the strength to get his student lobster license this summer and pull up traps at 7 a.m. 

Before Decker died, he was trying to figure out how he could buy Peter’s lobster and have it transported frozen across the country, to his home in Kansas. 

Decker was also working on his own approach. At one point, he helped another company with interest in LGMD raise nearly $5 million, Hesterlee, the MDA chief, recalled. That company pivoted away, but Decker started his own company, focused on a new non-viral gene therapy approach that might help older patients like himself and his sister June. He recruited top scientific leaders like Hesterlee to advise.

“And the fact that the company had no money didn’t faze him at all,” said Hesterlee. “You don’t underestimate Donavon ever, that was my advice to anyone. Sure. You know, he sounds like a Midwestern guy. He’s got kind of a low-key, slow way of talking. … Don’t let that make you think that he can’t make things happen, because he really could.”

A type of brain cell that plays a vital role in maintaining neural networks and repairing injuries lies at the core of a promising newly published Nature study on Alzheimer’s disease from the USF Health Byrd Alzheimer’s Center and Research Institute.

These cells are called microglia. To understand how they function, picture the vintage ’80s video game Pac-Man and the iconic character gobbling up everything in its maze-like path. In this case, however, it’s not tiny ghosts being devoured, but harmful proteins.

“Microglia are immune cells in the brain and they are scavengers,” said Gopal Thinakaran, PhD, CEO and endowed chair of the Byrd Institute. “They play an important role in clearing up debris in the brain. And they also have a very important role in Alzheimer’s disease.”

Microglia multiply as needed — think millions of Pac-Men and Ms. Pac-Men roaming neural pathways — to keep the brain debris-free.

“Imagine the brain as a bustling city, full of nerve cells or neurons, sending important messages back and forth,” Dr. Thinakaran said. “Microglia are like the city’s sanitation crew, emergency responders and even urban planners, all rolled into one. These tiny cells, making up about 10 percent of the brain, are incredibly important for keeping the city running smoothly and adapting to change.”

Microglia are constantly sending out feelers or projections to monitor the brain’s environment, searching for any signs of trouble, like infection, damage, or unwanted debris. And when they find it, they transform from their resting state to an active blob-like shape and engulf, in classic video-game style, harmful substances.

However, in aging individuals with diseased brains, microglia have a more difficult time keeping up with the garbage removal. Eventually, they succumb to the chronic pathology that permeates the brain, ultimately becoming sluggish and swollen, laden with oily lipids, and unable to remove fatty deposits of lipids efficiently.

 The factors that cause microglia to lose their effectiveness are part of the new study published Sept. 3 in the prestigious journal Nature, with Dr. Thinakaran serving as the co-senior author of an investigation done in collaboration with his former colleague Jubao Duan, PhD, at the University of Chicago and Endeavor Health Research Institute.

The paper shows how a variation in a particular gene, called PICALM, has a profound effect on the microglia. This change in the gene disrupts the microglia, heightening the likelihood of Alzheimer’s developing, explained Ari Sudwarts, PhD, co-first author on the paper and a postdoctoral research scholar in the Morsani College of Medicine.

“We made significant progress in understanding the functions of PICALM — the third-most significant risk gene for late-onset Alzheimer’s disease,” Dr. Sudwarts said. “We found that a variant of PICALM affected the immune cells of the brain, reducing their ability to clear debris, and causing a buildup of cholesterol and lipids. Understanding the functions disrupted by a specific risk gene gives new targets for developing pharmaceuticals for patients who have this genetic variant.”

Dr. Thinakaran is working to learn more about PICALM and other common genetic variants that also have a profound impact, increasing the risk of developing the disease.

“This is like gene mutations that cause cancer,” he said. “If you have such a mutation, you’re going to pass it on to your kids. There are only about three genes that have that kind of capability for Alzheimer’s disease. All the others are called risk factors — they don’t cause the disease in all people, but they increase one’s lifetime risk.”

He is fascinated by the challenge of figuring out how gene variants affect the disease, as well as how scientists can separate genetic effects from the lifestyle factors known to affect Alzheimer’s risk. 

“An individual’s risk in a lifetime becomes different, whether you exercise or not, whether you keep an active lifestyle or you’re highly educated and many other things,” Dr. Thinakaran said. “So it becomes really difficult to narrow down and study genetic impacts.”

But over the last two decades, genetic methods have become more advanced and zeroed in on “hotspots” in genes that increase one’s lifetime risk. One such hotspot is the PICALM gene, which is associated with a risk of developing late-onset Alzheimer’s.

Much research has focused on the PICALM gene, as well as the PICALM protein it produces, over the past two decades, including that done at the University of Chicago and Endeavor Health Research Institute by Dr. Duan. Dr. Thinakaran collaborated with Dr. Duan on a research grant to further study PICALM-related risk factors and received federal funding in 2019, just after Dr. Thinakaran moved to USF.

They oversaw a dual-lab study, involving cultured human-derived brain cells in petri dishes. Over time, this allowed them to gain a greater understanding of molecular changes in PICALM and the resulting increased risk of developing Alzheimer’s. They learned that 30 percent of the population has a certain variant, or allele, of the PICALM gene. Called the “minor allele” of PICALM, it appears to protect people against Alzheimer’s. But they wanted to understand the reason — the mechanism — for that.

When they examined the data in cultured cells, they found the answer lay in the Pac-Men of the brain — the microglia.

“Dr. Duan found that the risk allele in PICALM only showed up in microglia,” Dr. Thinakaran stated. “So we said, let’s introduce the change in the microglia, adding both the minor allele, which is protected from risk, and the major allele, which is not.”

As a result, they were able to find that the major allele reduces PICALM protein levels in the microglia. Having less PICALM protein damages organelles — functional structures within a cell — that degrade waste proteins called lysosomes. The less effective organelles disturb how proteins and lipids are managed in the cell, ultimately reducing the capacity for microglia to engulf protein material like amyloid and tau in the brain.

“This creates these compact structures called lipid droplets that cause further havoc in a cell, and it impedes the microglia from doing its job,” said Dr. Thinakaran. “It’s extremely rare to have a story develop like this, and it took five years to unfold.”

The take-away message?

“Many risks are being identified in microglia,” he said. “And we are giving kind of a roadmap for one risk, and how the process results in lipid dysregulation and how the further accumulation of lipid droplets really starts to make the microglia ineffective. The knowledge we have gained adds one more piece to the Alzheimer’s puzzle we are putting together.”

Reference: Kozlova A, Zhang S, Sudwarts A, et al. PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia. Nature. 2025. doi: 10.1038/s41586-025-09486-x

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“As people age, their cognitive ability tends to gradually decline,” Na said. “This is natural, and we saw that in this sample. But we also saw that people whose weight varied the most experienced more rapid cognitive declines.”

The researchers grouped participants based on how much their weight varied during the study. People whose weight varied the least demonstrated the lowest amount of cognitive decline, while people whose weight varied the most demonstrated between two and four times as much cognitive decline. This result also held true when the researchers compared variability in waist circumference and body mass index (BMI) to variability in cognitive decline.

In another analysis, the researchers found that both losing at least 5% of one’s weight and cycling between weight loss and gain of at least 5% of one’s weight were associated with faster cognitive decline. The results indicate the dangers of losing or fluctuating weight for older adults, Na said.

Older adults who gained weight demonstrated roughly the same level of cognitive decline as those whose weight remained stable. However, the researchers explained this does not suggest that gaining weight is a good idea for older adults.

“Mid-life obesity is a known risk factor for cognitive decline later in life, but there is an ‘obesity paradox’ associating late-life obesity with a healthier cognitive trajectory,” Na said. “Some studies have revealed a complex interplay between age-related muscle mass loss and fat gain in older adults, and our study does not suggest older adults should gain weight.”

The findings suggest that monitoring older adult weight could provide additional information that could be useful in protecting cognitive health, but, according to Na, individuals should not rely just on doctor visits to track weight.

“From one doctor’s appointment to the next, the way weight is measured may not be consistent,” Na said. “Perhaps you have your coat and shoes on one time, and the next time you are in light clothes and socks. To make sure you understand what is happening to their body and brain, older adults should track their weight at home in a more consistent way. For example, a person could weigh themselves around the same time in the morning after getting up, before breakfast and after a bathroom trip while wearing the same pajamas. This would provide them with very consistent data. Then, if their weight is not stable, they need to let their physicians know.”

Reference: Flores AC, Wennberg AM, Leung CW, Na M. Variability in body weight and body composition and cognitive trajectories in older adults in the United States. Obesity. 2025:oby.24309. doi: 10.1002/oby.24309

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The government of the Democratic Republic of the Congo on Thursday declared a new outbreak of Ebola in the central province of Kasai, the country’s 16th since 1976, as the World Health Organization warned that infections might rise further.

KINSHASA, Sept. 5 (Xinhua) — The government of the Democratic Republic of the Congo (DRC) on Thursday declared a new outbreak of Ebola in the central province of Kasai, the country’s 16th since 1976, as the World Health Organization (WHO) warned that infections might rise further.

DRC Health Minister Roger Kamba announced at a press conference in the capital of Kinshasa that the Zaire strain of the Ebola virus has re-emerged in the Bulape health zone, with 28 suspected cases reported, including 15 deaths. Four health workers were among the victims.

“These figures remain provisional, as investigations are still ongoing,” Kamba said, stressing that the announcement was guided by transparency and scientific rigor.

Samples tested on Sept. 3 at the DRC’s National Institute of Biomedical Research confirmed the cause of the outbreak as the Zaire strain, the WHO Regional Office for Africa said in a statement. “Case numbers are likely to increase as the transmission is ongoing,” it warned.

“The country has a stockpile of treatments, as well as 2,000 doses of the Ervebo Ebola vaccine, effective to protect against this type of Ebola, already prepositioned in Kinshasa that will be quickly moved to Kasai to vaccinate contacts and frontline health workers,” the WHO noted, adding that it is delivering two tonnes of supplies, including personal protective equipment, mobile laboratory equipment and medical supplies.

Meanwhile, it acknowledged that the affected area is hard to reach, taking at least one day of driving from the provincial capital Tshikapa, with few air links. “This is the starting phase of the response. We are too early to make an assessment,” said Patrick Otim, an officer at the WHO regional office, at an online briefing.

According to an early statement by the Ministry of Health, the index case was a 34-year-old pregnant woman admitted to Bulape General Reference Hospital on Aug. 20 with symptoms of sudden fever, multiple hemorrhages, bloody vomiting, and severe fatigue. She died on Aug. 25 from multiple organ failure.

The DRC last declared the end of an Ebola outbreak in September 2022, after one case was confirmed in the eastern province of North Kivu. Testing showed that the case was genetically linked to the 2018-2020 outbreak in North Kivu and Ituri provinces, which killed nearly 2,300 people.

Kasai previously reported Ebola outbreaks in 2007 and 2008, according to the WHO.

Ebola first occurred in 1976 in two simultaneous outbreaks: one was of Sudan virus disease in Nzara in what is now South Sudan, and the other was of Ebola virus disease in Yambuku, in what is now the DRC, then known as Zaire. The latter occurred in a village near the Ebola River, from which the disease takes its name, according to the WHO.

Ebola is a highly contagious hemorrhagic fever that causes a range of symptoms such as fever, vomiting, diarrhea, generalized pain, or malaise, and in many cases, internal and external bleeding.  ■

More than a decade ago, scientists harnessed a bacterial molecular machine that identifies and cuts specific sections of DNA, revolutionizing the ability to edit genes and accelerating research into treatments for all manner of diseases with a genetic link. But the technology known as CRISPR-Cas9 works by cutting DNA, not moving it. At Purdue University, researchers are investigating a similar molecular machine that moves so-called “jumping genes” into new locations in bacterial DNA, laying the groundwork for a more powerful gene-editing tool.

The team, led by Leifu Chang, a Purdue associate professor of biological sciences, has produced high-resolution structural snapshots of the Tn7-like transpososome, a complex of nucleic acids and proteins that can accurately cut and paste an entire gene from one location to another in the genome of a cell. This structural information is analogous to an exploded parts diagram for an engine, showing all the parts in atomic-level detail and how they work together. In a pair of papers published in the journal Cell in 2023 and 2024, the team captured the structure of all the components needed to understand how the molecular machine recognizes a jumping gene and the location in the genome where it will insert that gene.

“We’ve captured all the components that are really essential in this structure. This is a quite complicated process, requiring recognition of specific DNA in the gene and in the target and, while previous research has shown many partial structures, it’s important to see the whole picture,” said Chang, a member of the Purdue Institute for Cancer Research. “We’re providing a lot of information to understand how that process happens.”

Chang’s research is part of Purdue’s presidential One Health initiative, which involves research at the intersection of human, animal and plant health and well-being.

There are many similarities between the Tn7-like transpososome and the CRISPR system. CRISPR, which evolved as part of a bacterial defense system against known viral invaders, identifies and stores snippets of DNA from invaders between DNA brackets in a pattern called “clustered regularly interspersed short palindromic repeats,” hence CRISPR. Using the stored DNA as a template, the system generates an RNA mirror image of the viral DNA and surveils the cell looking for a match. When a match is made and an invader identified, a protein cuts the DNA of the viruses, blocking replication. The beauty of the system, from the standpoint of researchers, is that it uses RNA — a molecule easily synthesized in a lab — to identify and target DNA. By synthesizing an RNA snippet that searches for its own targets, researchers can use the system to snip DNA with precision.

But while CRISPR is great at what it does in bacteria, Chang said, it’s not a one-stop gene editing tool in human cells. For starters, cutting DNA in humans triggers a DNA repair pathway that could undo the cut or unintentionally introduce a mutation as part of the repair. Also, once the DNA is cut, it might not be repaired in which case the cell would die. Researchers have devised various workarounds, but they aren’t yet efficient and only work in dividing cells, putting repairs to cells that don’t divide, like neurons, out of reach.

By contrast, the transpososome is a complete package that includes the machinery for inserting genes. The transpososome facilitates the movement of transposons, or “jumping genes,” that can be copied and moved to different locations in the genome. Jumping genes make up about half of the genome in animal cells, including in humans, and are believed to increase genetic diversity.

“In general, breaking DNA to achieve genome editing is not ideal,” Chang said. “The transposon system is a more efficient approach because the proteins insert DNA seamlessly, so that avoids the harmful consequence of breaking DNA.”

Scientists who study the Tn7-like transpososome have discovered two pathways that it uses to find its target. The first uses a protein to directly recognize specific DNA sequences. The second is similar to CRISPR-Cas9, in that it uses a snippet of RNA as a guide to find the target. Chang, who is an expert in CRISPR-Cas systems, is interested in understanding how the CRISPR-type pathways work.

The two Cell papers taken together present complete cryo-electron microscopy structures of essential components in atom-by-atom detail. The structures show the point at which DNA attaches to two proteins, which triggers formation of the entire transpososome complex, and initiate transposition. As the 2024 paper states, “The findings provide mechanistic insights into targeted DNA insertion by Tn7-like transposons with implications for improving the precision and efficiency of their genome-editing applications.”

Chang said researchers are already trying to use the Tn7-like transpososome to edit animal cells but, so far, the process isn’t effective. While much work needs to be done to arrive at systems useful in nonbacterial cells, the full structural information he has provided will accelerate that work.

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