(Press-News.org) It is believed to be involved in the development of chronic inflammatory intestinal diseases, to trigger diabetes, to be responsible for obesity, even neurological diseases such as multiple sclerosis and Parkinson's could have their causes here - not to mention depressions and autistic disorders. We are talking about the microbiome - the vast collection of bacteria in the human gut. It is estimated that each person carries around 100 trillion bacterial cells in their digestive tract, belonging to several thousand species.
The microbiome has been the focus of research for 20 years - ever since a new technique made it possible to analyse these bacteria quickly and precisely: high-throughput sequencing. Since then, there has been an increasing body of findings that the microbiome, which is sometimes also referred to as the second human genome, is not only of central importance for digestion, but also influences, if not controls, at least a large number of body functions. The immune system is mentioned particularly frequently.
The microbiome influences the immune system
Scientists at the Universities of Würzburg and Marburg have now succeeded for the first time in experimentally demonstrating that bacterial metabolites are able to increase the cytotoxic activity of certain immune cells and thus positively influence the efficiency of tumour therapies. Ideally, the composition of the bacterial species in the microbiome could be used to control its influence on the success of the therapy.
The research team published the results of its study in the journal Nature Communications. Dr. Maik Luu, postdoc in the laboratory of Professor Michael Hudecek at the Medical Clinic and Polyclinic II of the University Hospital of Würzburg, was responsible for the finding. Another participant was Professor Alexander Visekruna from the Institute of Medical Microbiology and Hygiene at the Philipps University in Marburg, where Luu did research before moving to Würzburg.
Fatty acids increase the activity of killer cells
"We were able to show that the short-chain fatty acids butyrate and, in particular, pentanoate are able to increase the cytotoxic activity of CD8 T cells," Maik Luu describes the central result of the now published study. CD8 T cells are sometimes also called killer cells. As part of the immune system, it is their task to specifically kill cells that are harmful to the organism.
Short-chain fatty acids, in turn, belong to the most dominant class of metabolites of the gut microbiome. On the one hand, they can boost the metabolism of T cells by inducing central regulators of energy metabolism. On the other hand, they can inhibit specific enzymes that regulate the accessibility to the genetic material and thus the gene expression in the T cells. In doing so, they induce epigenetic changes.
Solid tumor models are combated more effectively
"When short-chain fatty acids reprogram CD8 T cells, one of the results is increased production of pro-inflammatory and cytotoxic molecules," Luu explains. In the experiment, treatment with the fatty acid pentanoate increased the ability of tumor-specific T cells to fight solid tumor models. "We were able to observe the same effect when fighting tumor cells with so-called CAR-T cells," says the scientist.
CAR-T cells are written out as "chimeric antigen receptor T cells". While normal T cells are largely "blind" to tumor cells, CAR T cells are able to recognize specific target antigens on the tumor surface and destroy the cancer cells thanks to a genetic modification. Michael Hudecek is one of the leading experts in the field of CAR-T cell research.
Targeted control via the composition of the microbiome
"The results are an example of how metabolites of intestinal bacteria can change the metabolism and gene regulation of our cells and thus positively influence the efficiency of tumor therapies," says Maik Luu. In particular, the use of CAR-T cells against solid tumors could benefit from this.
In these cases, therapy with genetically modified cells has so far been much less effective than the treatment of haematological tumours such as leukaemia. This could change if the CAR-T cells were treated with pentanoate or other short-chain fatty acids before being used in patients, the scientists hope.
This effect might specifically be exploited via the composition of the bacterial intestinal colonisation - especially since Luu and the others involved in the study were also able to identify the essential pentanoate producer of the intestinal flora: the bacterium Megasphaera massiliensis.
A long way to clinical applications
However, there is still a long way to go before the new findings will lead to new therapies for cancer patients. In a next step, the research team will initially expand the spectrum of tumour diseases investigated and, in addition to other solid tumours, also look at haematological tumour diseases such as multiple myeloma. In addition, it wants to investigate the functioning of short-chain fatty acids more intensively in order to identify starting points for targeted genetic modifications.
INFORMATION:
By Karina Toledo | Agência FAPESP* – A study conducted at the University of São Paulo (USP) in Brazil shows that the incidence of infections by the novel coronavirus among professional soccer players in São Paulo state during the 2020 season was 11.7%, the same as among health workers in the front line of the response to the pandemic.
To arrive at this number, the researchers retrospectively analyzed almost 30,000 RT-PCR tests performed on swabs from 4,269 athletes during eight tournaments of the São Paulo State Soccer Federation (FPF), the league responsible for organizing official championships in the state – six for men (the São Paulo Cup, Under-23s, U-20s, and the three divisions of the São Paulo Championship) and two for women (the ...
URBANA, Ill. - Food insecurity is a major problem in the U.S., and it worsened during the COVID-19 pandemic. The Supplemental Nutrition Assistance Program (SNAP) provides some relief, but millions of Americans still lack adequate access to healthy food. A new study from the University of Illinois proposes a potential solution.
"Restructuring SNAP as a Universal Basic Income (UBI) program or modified UBI is a straightforward way to eliminate food insecurity in United States. It's expensive but it is not difficult," says Craig Gundersen, distinguished professor in the Department of Agricultural and Consumer Economics at U of I. Gundersen authored the study, published ...
Tsukuba, Japan - Extended exposure to light during nighttime can have negative consequences for human health. But now, researchers from Japan have identified a new type of light with reduced consequences for physiological changes during sleep.
In a study published in June 2021 in Scientific Reports, researchers from University of Tsukuba compared the effects of light-emitting diodes (LEDs), which have been widely adopted for their energy-saving properties, with organic light-emitting diodes (OLEDs) on physical processes that occur during sleep.
Polychromatic white LEDs emit a large amount ...
Tsukuba, Japan - Scientists from the Division of Physics at the University of Tsukuba used the quantum effect called "spin-locking" to significantly enhance the resolution when performing radio-frequency imaging of nitrogen-vacancy defects in diamond. This work may lead to faster and more accurate material analysis, as well as a path towards practical quantum computers.
Nitrogen-vacancy (NV) centers have long been studied for their potential use in quantum computers. A NV center is a type of defect in the lattice of a diamond, in which two adjacent carbon atoms have been replaced with a nitrogen atom and a void. This leaves an unpaired electron, which can be detected using radio-frequency waves, because its probability of emitting a photon ...
The discovery of the first high-temperature superconductor in 1986 brought with it the hope that superconductivity would one day revolutionise power transmission, electronic devices and other technologies. Materials that show superconductivity (zero electrical resistance) generally do so at an extremely low temperature. For their use to become widespread and world-changing, we need to develop a material that is superconducting close to room temperature. Research showed that the first high-temperature superconductor - a copper oxide compound - was part of a ...
Anyone who likes to sing in the shower probably knows that they sometimes sing out of tune. But what about professional singers? How well do they evaluate their own abilities? And what role does this self-assessment play in becoming a better musician? A research team from the Max Planck Institute for Empirical Aesthetics in Frankfurt, New York University, and the University of Hamburg has now investigated these questions scientifically in a study of professional singers.
The study participants, all female sopranos, were each recorded singing "Happy Birthday" in a studio. They were then asked to listen to all of the recordings and rate the pitch accuracy of both their ...
Babies younger than four weeks old, called neonates, were once thought not to perceive pain due to not-yet-fully-developed sensory systems, but modern research says otherwise, according to researchers from Hiroshima University in Japan.
Not only do babies experience pain, but the various levels can be standardized to help nurses recognize and respond to the babies' cues -- if the nurses have the opportunity to learn the scoring tools and skills needed to react appropriately. With tight schedules and limited in-person courses available, the researchers theorized, virtual e-learning may be able to provide a path forward for nurses to independently pursue training in this area.
To test this hypothesis, researchers conducted a pilot study ...
Drs. Nobuo Noda (Director) and Tatsuro Maruyama (Researcher) et al. at the Institute of Microbial Chemistry (BIKAKEN, Tokyo, Japan) discovered that lipidated Atg8(1), the most famous factor that mediates autophagy, has membrane perturbation activity and elucidated that this activity is responsible for efficient autophagosome formation.
Autophagosome formation is an essential step in determining the target of degradation in autophagy, which is one of the mechanisms of intracellular protein degradation. It is known that lipidated Atg8 plays a primary role in autophagy processes; however, the molecular function of lipidated Atg8 on the autophagy-related ...
A new study from Queen Mary University of London has demonstrated that immune cells can be stimulated to assemble into special structures within pancreatic cancer such that, at least in a pre-clinical model, researchers can demonstrate an improvement in the efficacy of chemotherapy.
The body's immune system is a critical defence against illness such as infections, as has been highlighted by the recent COVID-19 pandemic. The same immune system can also help us fight cancer. However, pancreatic cancer is different; a key feature of this cancer type is that the pancreatic cancer cells are surrounded by a dense, impenetrable barrier known as the stroma, which often blocks the access of immune cells to ...
Coral reefs are a favorite spot for scuba divers and are among the world's most diverse ecosystems. For example, the Hawaiian coral reefs, known as the "rainforests of the sea," host over 7,000 species of marine animals, fishes, birds and plants. But coral reefs are facing serious threats, including a number of diseases that have been linked to human activity.
To understand the connection between human activity and a type of tumorlike disease called growth anomalies (GAs), researchers at the National Institute of Standards and Technology (NIST) have collaborated with the U.S Geological Survey (USGS) and the National ...
