Publisher Health

The gut microbiome, a community of trillions of microbes living in the human intestines, has an increasing reputation for affecting not only gut health but also the health of organs distant from the gut. For most microbes in the intestine, the details of how they can affect other organs remain unclear, but for gut resident bacteria L. reuteri the pieces of the puzzle are beginning to fall into place.
“L. reuteri is one of such bacteria that can affect more than one organ in the body,” said co-corresponding author Dr. Sara Di Rienzi, assistant professor of molecular virology and microbiology at Baylor. “Researchers have found that these bacteria reduce gut inflammation in adults and rodent models, suppress bone loss in animal models of osteoporosis and in a human clinical trial, promote skin wound healing in mice and humans and improve social behavior in six mouse models of autism spectrum disorder.”
Of those effects of L. reuteri, the abilities to promote social behavior and wound healing have been shown to require signaling by the hormone oxytocin, but little was known about how this occurs.
“We investigated the link connecting L. reuteri, oxytocin and distant organs such as the brain and uncovered unexpected findings,” said first author Dr. Heather Danhof, assistant professor of molecular virology and microbiology at Baylor. “Oxytocin is mostly produced in the hypothalamus, a brain region involved in regulating feeding and social behavior, as well as in other organs. Given that other brain-produced hormones also are made in the gut, we tested the novel idea that oxytocin itself was also produced in the intestinal epithelium where L. reuteri typically resides.”
The researchers built up their case step by step. First, they reviewed single-cell RNA-Seq datasets of the intestinal epithelium, which show which genes are expressed in that tissue. They found that oxytocin genes are expressed in the epithelium of various species, including mice, macaques and humans. Then, using fluorescence microscopy, the team revealed the presence of oxytocin directly on human intestinal organoids, also called mini guts, which are laboratory models of intestinal tissue that recapitulate many of its functions and structure.
“Finally, a big moment was when we visualized oxytocin in human intestinal tissue samples, demonstrating oxytocin as an intestinal hormone,” Di Rienzi said.
“We also determined a mechanism by which L. reuteri mediates oxytocin secretion from human intestinal tissue and human intestinal organoids,” Danhof said. “L. reuteri stimulates enteroendocrine cells in the intestine to release the gut hormone secretin, which in turn stimulates another intestinal cell type, the enterocyte, to release oxytocin.”
“We are excited about these findings,” said co-corresponding author Dr. Robert Britton, professor of molecular virology and microbiology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “These bacteria have positive effects in various parts of the body, but it was not understood how that happened. Our findings reveal that oxytocin is also produced in the gut and a new mechanism by which L. reuteri affects oxytocin secretion. Now, we are working to identify potential treatments for autism spectrum disorders using a new mouse model deficient in intestinal oxytocin to gain a new understanding of the connection between oxytocin produced in the gut, social behavior and the brain.”

Cancer cells hijack normal biological processes, allowing them to multiply. For example, tumors spur construction of new blood vessels, building themselves “highways” to supply nutrients.
Researchers have known about cancer’s blood vessel infiltration for decades, but it was only in the past few years that Stanford Medicine scientists and their colleagues discovered that tumors don’t just tap the body’s highway system; they can also infiltrate and exploit its “telecommunications.”
To put it in physiologic terms, tumors don’t just grow blood vessels; they also wire themselves into the nervous system. Certain brain cancers form working electrical connections with nearby nerves, then use the nerves’ electrical signals for their own purposes, the research has shown. The latest findings, published Nov. 1 in Nature, demonstrate that these tumors can even hijack the biological machinery of brain plasticity — which enables learning — to drive their own growth.
The discoveries have opened a novel field of medicine called cancer neuroscience. It offers new opportunities to target some of the deadliest forms of cancer, including brain tumors that are almost always lethal. Scientists are especially intrigued by the cancer treatment potential of FDA-approved drugs developed for other neurological disorders, such as epilepsy. It turns out that several such medications interrupt neural signals now understood to fuel certain cancers.
“Since 2015, when we first published that neuronal activity actually drives the growth of cancer in multiple brain tumor types, there has been a very exciting explosion of studies on these interactions,” said Michelle Monje, MD, PhD, a professor of neurology and neurological sciences and senior author of the new Nature study, whose team’s discoveries form the foundation of cancer neuroscience. “This is clearly a major set of interactions crucial to tumor biology that we had missed.”
Tumors’ hidden talent
Why did cancer’s ability to twine into the nervous system stay hidden from researchers for so long? A focus on how malignant and healthy cells differ may provide an explanation.

Brain health in over 50s deteriorated more rapidly during the pandemic, even if they didn’t have COVID-19, according to major new research linking the pandemic to sustained cognitive decline.
Researchers looked at results from computerised brain function tests from more than 3,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. The remote study, led by teams at the University of Exeter and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, tested participants’ short term memory and ability to complete complex tasks.
Through analysing the results from this big dataset, researchers found that cognitive decline quickened significantly in the first year of the pandemic, when they found a 50 per cent change to the rate of decline across the study group. This figure was higher in those who already had mild cognitive decline before the pandemic, according to the research published in The Lancet Healthy Longevity.
This continued into the second year of the pandemic, suggesting an impact beyond the initial 12-month period of lockdowns. The researchers believe this sustained impact to be particularly relevant to ongoing public health and health policy.
The cognitive decline seems to have been exacerbated by a number of factors during the pandemic, including an increase in loneliness and depression, a decrease in exercise and higher alcohol consumption. Previous research has found that physical activity, treating existing depression, getting back into the community and reconnecting with people, are all important ways to reduce dementia risk and maintain brain health.
Anne Corbett, Professor of Dementia Research and PROTECT Study Lead at the University of Exeter, said: “Our findings suggest that lockdowns and other restrictions we experienced during the pandemic have had a real lasting impact on brain health in people aged 50 or over, even after the lockdowns ended. This raises the important question of whether people are at a potentially higher risk of cognitive decline which can lead to dementia. It is now more important than ever to make sure we are supporting people with early cognitive decline, especially because there are things they can do to reduce their risk of dementia later on. So if you are concerned about your memory the best thing to do is to make an appointment with your GP and get an assessment.
“Our findings also highlight the need for policy-makers to consider the wider health impacts of restrictions like lockdowns when planning for a future pandemic response.”
Professor Dar Aarsland, Professor of Old Age Psychiatry at King’s IoPPN, said “This study adds to the knowledge of the long-standing health-consequences of COVID-19, in particular for vulnerable people such as older people with mild memory problems. We know a great deal of the risks for further decline, and now can add COVID-19 to this list. On the positive note, there is evidence that life-style changes and improved health management can positively influence mental functioning. The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

The slowdown of physical activity during adolescence is not likely caused by lifestyle and environment but by energy demands placed on the body as it grows and sexually matures, according to a new study by researchers at the University of Colorado Anschutz Medical Campus.
The study, published today in the Proceedings of the Royal Society B, examined the lifestyles of the physically active Tsimane people, an indigenous population of forager-horticulturalists in lowland Bolivia, to see similarities and differences to adolescents living in post-industrialized nations.
“We wanted to look at the role of environment and the role of biology,” said the study’s lead author Ann E. Caldwell, PhD, assistant professor of medicine specializing in endocrinology and metabolism at the University of Colorado School of Medicine. “These changes are normally thought to be associated with psychosocial changes that happen in adolescence in technologically advanced societies, but we looked at this from an evolutionary standpoint.”
The Tsimane had minimal hypertension, coronary artery disease and ate mostly what they grew or hunted. Their levels of physical activity were far higher than those in post-industrialized societies. Yet, at older ages they also do less physical activity during adolescence, like their cohorts in other cultures.
Scientists know that physical activity declines with age and that males are more active than females. The steepest age-related declines in physical activity occur in adolescence and at earlier ages in girls in several post-industrialized countries. The lack of physical activity is one of the biggest predictors of chronic disease. Recent studies found that 28% of adults worldwide are insufficiently active, while a staggering 80% of adolescents worldwide fall into this category. This is defined as less than 150 minutes a week of at least moderate intensity activity for adults and less than 420 minutes a week for children and adolescents.
“Adolescence is a life stage characterized by distinct endocrinological, anatomical and cognitive changes that likely require substantial energetic resources, though the energetic costs of these hormones and related physiological sequelae have not been fully quantified,” Caldwell said.
As the body rapidly grows, it requires massive energy boosts to build muscle, bone, neural connections and the elements of sexual maturity. High levels of physical activity at this time and low levels of food will delay sexual maturity. Girls in particular pay a higher price for physical activity since it can slow down sexual maturation, critical from an evolutionary standpoint.

In the immune system, chronic infections and the defence against tumors often lead to the phenomenon of T cell exhaustion: In this process, the T lymphocytes gradually lose their function, which impairs their responses against cancer and infections. The molecular mechanisms that control this loss of function have not been fully unraveled.
It is now certain that the exhaustion process is significantly influenced by the “powerhouses of the cells,” the mitochondria.
When mitochondrial respiration fails, a cascade of reactions is triggered, culminating in the genetic and metabolic reprogramming of T cells — a process that drives their functional exhaustion. But this “burnout” of the T cells can be counteracted: pharmacological or genetic optimization of cellular metabolism increases the longevity and functionality of T cells. This can be achieved, for example, by overexpressing a mitochondrial phosphate transporter that drives the production of the energy-providing molecule adenosine-triphosphate.
These discoveries are reported by a team led by Dr. Martin Vaeth at the Institute for Systems Immunology at Julius-Maximilians-Universität (JMU) Würzburg in the journal Nature Communications. “We are optimistic that our findings will contribute to the improvement of cancer immunotherapy,” the scientist says.
Possible Improvement of CAR-T Cell Therapy
One example: CAR-T cell therapy has demonstrated remarkable efficacy in the treatment of leukemia and lymphoma. CAR-T cells are lymphocytes that that have been engineered in the laboratory to fight the respective form of cancer. However, when it comes to solid tumors, CAR-T cells also tend to exhaustion, limiting their success in this context.
“Our experiments demonstrate that augmented mitochondrial metabolism also increases the longevity and functionality of virus-specific T cells in chronic infections,” says the JMU scientist. It is plausible that this strategy can be also harnessed to enhance T-cell-based immunotherapies for cancer therapy.

Compact genetic testing device created for Covid-19 could be used to detect a range of pathogens, or conditions including cancer.
A virus diagnosis device that gives lab-quality results within just three minutes has been invented by engineers at the University of Bath, who describe it as the ‘world’s fastest Covid test’.
The prototype LoCKAmp device uses innovative ‘lab on a chip’ technology and has been proven to provide rapid and low-cost detection of Covid-19 from nasal swabs. The research team, based at the University of Bath, say the technology could easily be adapted to detect other pathogens such as bacteria — or even conditions like cancer.
The device works by rapidly releasing and amplifying genetic material from a nasal swab sample by carrying out a chemical reaction to produce a result, which can be viewed on a smartphone app.
Unlike lateral flow assay tests, commonplace during the pandemic, the LoCKAmp employs the same ‘gold standard’ genetic-based testing techniques previously reserved for lab-based PCR (polymerase chain reaction) tests, thus enabling rapid testing at laboratory-scale standard for the first time.
As well as its accuracy, the speed of the LoCKAmp sets it apart. With results shown within three minutes, the research team say that to their knowledge this makes LoCKAmp the fastest Covid-19 test reported to date.
Made with off-the-shelf components and factory-manufactured printed circuit boards, the prototype device could be made on a mass scale quickly and at low cost, presenting care providers and public health bodies around the world with an effective new tool in virus detection. The research team says a commercial partner with the relevant design and manufacturing expertise could quickly redesigned the LoCKAmp into a small, portable device — with great potential for use in remote healthcare settings.

Antibiotic-resistant bacteria pose a major challenge to healthcare systems worldwide. Due to numerous resistance mechanisms, infections with the pathogen Pseudomonas aeruginosa are particularly feared. Researchers at the German Center for Infection Research (DZIF), the University Hospital Cologne, the Helmholtz Centre for Infection Research in Braunschweig and the University Medical Center Hamburg-Eppendorf have now discovered antibodies that could lead to a highly potent treatment option of acute and chronic infections with P. aeruginosa. The study was published in the scientific journal Cell.
Antibiotic-resistant bacteria pose a growing threat worldwide, not only to infected patients but also to our health systems as a whole. In particular, infections with the bacterium Pseudomonas aeruginosa are feared due to numerous resistance mechanisms and can lead to complicated lung and bloodstream infections, especially in seriously ill patients. In addition, the pathogen can permanently colonise organs such as the lungs, where it promotes progressive tissue damage. Often, so-called antibiotics of last resort have to be used in infected patients because the standard therapies are no longer effective. New therapeutic approaches are therefore urgently needed to ensure effective treatment of infections with multidrug-resistant pathogens such as P. aeruginosa in the future.
Researchers from the German Center for Infection Research (DZIF) and the University Hospital Cologne, together with colleagues from the Helmholtz Centre for Infection Research in Braunschweig and the University Medical Center Hamburg-Eppendorf, have now succeeded in isolating and characterising highly effective antibodies against this pathogen from immune cells of cystic fibrosis patients who were chronically infected with P. aeruginosa.
Research approach adopted from the development of antiviral therapies
“Many of the highly effective and broadly neutralising monoclonal antibodies used against viruses were isolated from infected, recovered or vaccinated individuals and then further developed for clinical use,” explains Dr Alexander Simonis, first author of the study, assistant physician in the Department of Infectiology and head of the junior research group “Immunotherapies against bacterial infections” at the University Hospital Cologne.
In their study, the researchers therefore investigated whether the approach of isolating and recombinantly expressing broadly neutralising antibodies from human immune cells, which has been successful for viral infections, can also be used to develop new therapies against bacterial infections. In order to find suitable antibodies, they focused on patients with cystic fibrosis, whose lungs are often chronically colonised with P. aeruginosa. The researchers hypothesised that repeated exposure to the bacterium in these patients would lead to the development of antibodies able to effectively inhibit the virulence of P. aeruginosa. Thanks to a robust screening test, the researchers indeed found monoclonal antibodies in the blood samples of some cystic fibrosis patients that are able to neutralise the virulence of the bacterium.
Antibodies as pathoblockers: successful inhibition of bacterial virulence
The mode of action of these antibodies is based on blocking an important virulence factor of the bacterium, the so-called type III secretion system, which plays an important role especially in severe infections with P. aeruginosa. In extensive experiments with cell culture and animal models, the researchers were able to show that the newly developed antibodies are just as effective against the bacterium as classical antibiotics. However, since the activity of these antibodies is independent of the mechanisms of action of conventional antibiotics, these so-called pathoblockers can also — in contrast to many classical antibiotics — be effective against highly resistant bacteria.

Imagine a skin cream that heals damage occurring throughout the day when your skin is exposed to sunlight or environmental toxins. That’s the potential of a synthetic, biomimetic melanin developed by scientists at Northwestern University.
In a new study, the scientists show that their synthetic melanin, mimicking the natural melanin in human skin, can be applied topically to injured skin, where it accelerates wound healing. These effects occur both in the skin itself and systemically in the body.
When applied in a cream, the synthetic melanin can protect skin from sun exposure and heals skin injured by sun damage or chemical burns, the scientists said. The technology works by scavenging free radicals, which are produced by injured skin such as a sunburn. Left unchecked, free radical activity damages cells and ultimately may result in skin aging and skin cancer.
The study will be published Nov. 2 in Nature npj Regenerative Medicine.
Melanin in humans and animals provides pigmentation to the skin, eyes and hair. The substance protects your cells from sun damage with increased pigmentation in response to sunlight — a process commonly referred to as tanning. That same pigment in your skin also naturally scavenges free radicals in response to damaging environmental pollution from industrial sources and automobile exhaust fumes.
“People don’t think of their everyday life as an injury to their skin,” said co-corresponding author Dr. Kurt Lu, the Eugene and Gloria Bauer Professor of Dermatology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine dermatologist. “If you walk barefaced every day in the sun, you suffer a low-grade, constant bombardment of ultraviolet light. This is worsened during peak mid-day hours and the summer season. We know sun-exposed skin ages versus skin protected by clothing, which doesn’t show age nearly as much.”
The skin also ages due to chronological aging and external environmental factors, including environmental pollution.

A research team has discovered antibodies that could lead to a new approach to treating acute and chronic infections with the bacterium Pseudomonas aeruginosa. Due to its numerous resistance mechanisms, P. aeruginosa is associated with high morbidity and mortality and can cause complicated infections and dangerous cases of sepsis in severely ill patients. The team of scientists from the University of Cologne, University Hospital Cologne, the Helmholtz Centre for Infection Research in Braunschweig and University Hospital Hamburg-Eppendorf isolated the antibodies from immune cells of chronically ill patients and described their binding mechanisms. The study ‘Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa’ was published in the scientific journal Cell.
Antibiotic-resistant bacteria are a crucial health concern worldwide not only to infected people, but also to our healthcare systems in general. Infections with the bacterium P. aeruginosa in particular are a threat due to numerous resistance mechanisms, often leading to complicated infections of the lungs and dangerous sepsis, especially in severely ill patients. In addition, the pathogen can permanently colonize organs such as the lungs, where it promotes progressive tissue damage. Often, so-called last-resort antibiotics must be used to treat infected patients, as the standard treatments no longer work. New therapeutic approaches are therefore urgently needed to ensure effective treatment for infections with multi-resistant pathogens such as P. aeruginosa in the future.
In their study, the researchers therefore investigated whether the approach of isolating broadly neutralizing human antibodies, which has been successful for viral infections, could also be used for the development of new therapies against bacterial infections. “Many of the therapeutic antibodies that are already being used against viruses have been isolated and developed from infected, recovered or vaccinated individuals,” said lead author Dr Alexander Simonis, resident physician at the Infectiology Department of Department I of Internal Medicine and head of the BMBF-funded junior research group ‘Immunotherapies against bacterial infections’ at the UoC’s Center for Molecular Medicine Cologne.
The research team isolated highly effective antibodies against this pathogen from immune cells of patients with cystic fibrosis who were chronically infected with P. aeruginosa. These antibodies block an important virulence factor of the bacterium, the so-called type III secretion system, which plays an important role especially in severe infections with P. aeruginosa. In extensive experiments using cell cultures and animal models, the researchers were able to show that the newly developed antibodies are as effective against the bacterium as conventional antibiotics. However, since the activity of these antibodies is independent of the mechanisms of action and resistance of antibiotics, these so-called pathoblockers can also — in contrast to many conventional antibiotics — work on highly resistant bacteria.
“The findings and the experimental approaches can also be transferred to other bacterial pathogens and thus represent a promising new approach for the treatment of infections with multi-resistant bacteria,” concluded the last author of the study, lecturer (Privatdozent) Dr Jan Rybniker, physician at the Infectiology Department of Department I for Internal Medicine and head of the ‘Translational Research Unit — Infectious Diseases’ at University Hospital Cologne and the UoC’s Center for Molecular Medicine Cologne.
The study was conducted with funding from the Clinician Scientist Programme of the UoC’S Faculty of Medicine, the Career Advancement Program of the Center for Molecular Medicine Cologne as well as from the funding measure ‘Young Researchers Groups in Infection Research’ by the Federal Ministry of Education and Research, which has supported Dr Simonis since May 2022 with a junior research group.
The scientists are now planning to further develop the antibodies and to test them in clinical trials. In the long term, they plan to use the antibodies as part of a new therapeutic approach, especially in acute and severe infections with P. aeruginosa. According to the researchers, the antibodies also offer the possibility to protect patients with an increased risk of P. aeruginosa infections — especially in intensive care units or in the case of cancer — by means of passive immunization.

Atherosclerosis is considered a frequent cause of cardiovascular diseases and strokes. Despite medical progress, case numbers are constantly rising. Targeted new therapeutic approaches are therefore more important than ever. An international team led by Professor Christian Weber, Director of the Institute for Cardiovascular Prevention (IPEK) at the University Hospital of Munich, and Professor Donato Santovito, leader of the Translational Vascular Therapy research group at IPEK, has now identified a specific microRNA molecule as a promising starting point for the investigation of new therapies.
Some time ago, the researchers had already demonstrated that the transmembrane protein CXCR4 plays a significant role in the development of atherosclerosis. The protein transmits signals to the cell interior. If CXCR4 is specifically silenced in arterial endothelial cells or in smooth muscle cells, it results in more severe atherosclerotic lesions. At the same time, there is increased leukocyte ingress into the cell, which leads to inflammatory processes. With regard to leukocytes, however, the presence of CXCR4 can also promote the development of inflammatory processes. “It made sense, therefore, to only boost the expression of CXCR4 on the cells of the vascular wall in order to counteract the atherosclerosis,” says Santovito. “The challenge, however, is not to influence any biological processes, as the protein occurs in all cells and exercises various important functions.”
Blockade molecule intervenes in signaling pathway
Using databases, molecular biological screening in cell cultures, and mouse models, the researchers therefore searched specifically for microRNA molecules that are limited to vascular cells and are involved in the regulation of CXCR4. And indeed, they managed to identify a good therapeutic starting point for the treatment of atherosclerosis in the form of miR-206, a candidate which occurs only in endothelial cells and in vascular smooth muscle cells. In those sites, it downregulates the expression of CXCR4 by binding to the transcripts of the CXCR4 gene and preventing their conversion into the protein.
For therapeutic application, the effect of miR-206 needs to be suppressed. To this end, the researchers developed a so-called target-site blocker (TSB): a molecule that specifically interrupts interactions between miR-206 and the CXCR4 transcripts and thus only boosts its expression in the respective cells. The researchers were able to demonstrate the effectiveness of this approach in a mouse model and in human cells in the culture. Most notably, the blocker they developed was able to prevent atherosclerosis in the mouse model.
“Eliminating miRNA-mediated gene suppression represents an attractive, feasible, and cost-effective method for fine-tuning gene expression at the cell-specific level,” summarizes LMU researcher Weber. Tissue-specific miRNA regulation pathways are prevalent and are considered to be a specific therapeutic target for a wide variety of diseases.
As their next step, the researchers plan to evaluate their results in preclinical studies with larger animal models within the framework of the German Cardiovascular Research Centre (DZHK) and the Cluster for Nucleic Acid Therapeutics Munich (CNATM).