Changes in gut microbiota influence which patients get AIG-related neuroendocrine tumors

Researchers took biopsies of AIG patients with and without neuroendocrine tumor growth to understand their bacterial communities
Image Credit: Osaka Metropolitan University

Researchers from Osaka Metropolitan University have discovered how the balance of bacteria in the stomach affects the growth of neuroendocrine tumors (NETs). By identifying the specific bacteria involved and the biochemical reactions that cause tumor growth, the researchers hope to create a new diagnostic technique to detect which patients are most likely to develop cancer.

Autoimmune gastritis (AIG) is a long-term condition in which the body’s immune system mistakenly attacks the lining of the stomach. This ongoing immune response gradually damages the stomach, affecting how it functions and its ability to protect itself from harmful agents. Over time, these changes can increase the risk of developing NETs, a type of tumor that develops from hormone-producing cells in the stomach.

Drawing a Line from the Gut Microbiome to Inflammation and Depression

Morganella morganii bacteria on a plate.
Photo Credit: Ajay Kumar Chaurasiya
(CC BY-SA 4.0)

It’s become increasingly clear that the gut microbiome can affect human health, including mental health. Which bacterial species influence the development of disease and how they do so, however, is only just starting to be unraveled.

For instance, some studies have found compelling links between one species of gut bacteria, Morganella morganii, and major depressive disorder. But until now no one could tell whether this bacterium somehow helps drive the disorder, the disorder alters the microbiome, or something else is at play.

Harvard Medical School researchers have now pinpointed a biologic mechanism that strengthens the evidence that M. morganii influences brain health and provides a plausible explanation for how it does so.

The findings, published in the Journal of the American Chemical Society, implicate an inflammation-stimulating molecule and offer a new target that could be useful for diagnosing or treating certain cases of the disorder. They also provide a roadmap for probing how other members of the gut microbiome influence human health and behavior.

“There is a story out there linking the gut microbiome with depression, and this study takes it one step further, toward a real understanding of the molecular mechanisms behind the link,” said senior author Jon Clardy, the Christopher T. Walsh, PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.

Altered gut bacteria may be early sign of Alzheimer’s disease

 

Alzheimer’s disease causes changes to the brain that begin two decades or more before symptoms appear. A study by researchers at Washington University School of Medicine in St. Louis reveals that the bacteria that live in the gut also change before Alzheimer’s symptoms arise, a discovery that could lead to diagnostics or treatments for Alzheimer’s disease that target the gut microbiome.
Image Credit: Gerd Altmann

People in the earliest stage of Alzheimer’s disease — after brain changes have begun but before cognitive symptoms become apparent — harbor an assortment of bacteria in their intestines that differs from the gut bacteria of healthy people, according to a study by researchers at Washington University School of Medicine in St. Louis.

The findings, published June 14 in Science Translational Medicine, open up the possibility of analyzing the gut bacterial community to identify people at higher risk of developing dementia, and of designing microbiome-altering preventive treatments to stave off cognitive decline.

“We don’t yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case,” said co-corresponding author Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine. “It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer’s disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease.”

Brain-Belly Connection: Gut Health May Influence Likelihood of Developing Alzheimer’s

UNLV study pinpoints 10 bacterial groups associated with Alzheimer’s disease, provides new insights into the relationship between gut makeup and dementia.
Illustration Credit: Julien Tromeur

Could changing your diet play a role in slowing or even preventing the development of dementia? We’re one step closer to finding out, thanks to a new UNLV study that bolsters the long-suspected link between gut health and Alzheimer’s disease.

The analysis — led by a team of researchers with the Nevada Institute of Personalized Medicine (NIPM) at UNLV and published this spring in the Nature journal Scientific Reports — examined data from dozens of past studies into the belly-brain connection. The results? There’s a strong link between particular kinds of gut bacteria and Alzheimer’s disease.

Between 500 and 1,000 species of bacteria exist in the human gut at any one time, and the amount and diversity of these microorganisms can be influenced by genetics and diet.

The UNLV team’s analysis found a significant correlation between 10 specific types of gut bacteria and the likelihood of developing Alzheimer’s disease. Six categories of bacteria — Adlercreutzia, Eubacterium nodatum group, Eisenbergiella, Eubacterium fissicatena group, Gordonibacter, and Prevotella9 — were identified as protective, and four types of bacteria — Collinsella, Bacteroides, Lachnospira, and Veillonella — were identified as a risk factor for Alzheimer’s disease.

Your gut senses the difference between real sugar and artificial sweetener

A section of mouse intestines shows in green the relatively scarce neuropod cells in the epithelium that are responsible for communicating conditions inside the gut to the nervous system outside. 
Credit: Borhoquez Lab, Duke

Your taste buds may or may not be able to tell real sugar from a sugar substitute like Splenda, but there are cells in your intestines that can and do distinguish between the two sweet solutions. And they can communicate the difference to your brain in milliseconds.

Not long after the sweet taste receptor was identified in the mouths of mice 20 years ago, scientists attempted to knock those taste buds out. But they were surprised to find that mice could still somehow discern and prefer natural sugar to artificial sweetener, even without a sense of taste.

The answer to this riddle lies much further down in the digestive tract, at the upper end of the gut just after the stomach, according to research led by Diego Bohórquez, an associate professor of medicine and neurobiology in the Duke University School of Medicine.

In a paper appearing Jan. 13 in Nature Neuroscience, “we’ve identified the cells that make us eat sugar, and they are in the gut,” Bohórquez said. Infusing sugar directly into the lower intestine or colon does not have the same effect. The sensing cells are in the upper reaches of the gut, he said.

Messengers from gut to brain

 

Thomas Korn is a professor for Experimental Neuroimmunology at TUM.
Image: Magdalena Jooss / TUM

Scientists have long been aware of a link between the gut microbiome and the central nervous system (CNS). Until now, however, the immune cells that move from the gut into the CNS and thus the brain had not been identified. A team of researchers in Munich has now succeeded in using violet light to make these migrating T cells visible for the first time. This opens up avenues for developing new treatment options for diseases such as multiple sclerosis (MS) and cancer.

The link between the gut microbiome and the CNS, known as the gut/brain axis (GBA), is believed to be responsible for many things: a person’s body weight, autoimmune diseases, depression, mental illnesses and Alzheimer’s disease. Researchers at the Technical University of Munich (TUM) and LMU University Hospital Munich have now succeeded in making this connection visible for the first time. This is cause for hope – for those suffering from MS, for example. It may offer ways to adapt treatments, and T cells could perhaps be modified before reaching the brain.

The immune system is affected by environmental factors – also in the central nervous system in case of MS patients. This autoimmune disease is subject to repeated flare-ups, experienced by patients as the improvement or worsening of their condition. T cells collect information and, in MS patients, carry it to the central nervous system (in the brain or spinal cord) where an immune response is triggered. Until now, however, it was long uncertain how and from where the T cells were traveling to the CNS.

The team working with Thomas Korn, a professor of experimental neuroimmunology at TUM, has developed a method for marking immune cells in mice using photoconvertible proteins. The T cells can then be made visible with violet light. The researchers successfully tested this method with the mouse model in lymph nodes, both in the gut and the skin. They were able to track the movement of the T cells from those locations into the central nervous systems.

T cells from the skin migrated into the gray and white matter of the CNS, while almost all T cells from the gut ended up in the white matter. For T cells in the brain, it was still possible to determine their origin. “What makes these insights so important is that they demonstrate for the first time that environmental influences impact the T cells in lymph nodes in the gut and the skin, which then carry this information into the distant organs,” says Prof. Thomas Korn. “The characteristics of the T cells are sufficiently stable for us to determine whether immune responses are influenced by skin or gut T cells,” adds LMU researcher Dr. Eduardo Beltrán, who performed the bioinformatic analyses in this study.

An important insight for MS patients: “If gut or skin cells were known to be the cause, the T cells could be treated at the source of the disease and predictions could be made on the progress of the chronic inflammation and autoimmune condition,” says first author Michael Hiltensperger. The results of the study could also mean a breakthrough for research on other autoimmune diseases or cancer.

Paper released in publication Nature Immunology

Source/Credit: Technical University of Munich

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