A Mass Extinction Is Taking Place in the Human Gut

In November 2022, Swiss scientists opened an eagerly awaited package from rural Ethiopia. It was full of shit. For two months, public health researcher Abdifatah Muhummed had been collecting stool samples from children in a remote, pastoralist community in Ethiopia’s Somali Region, as part of a global effort to catalog and preserve the diversity of human gut bacteria. He split each sample into four tubes, froze them at –80 degrees Celsius, and shipped two of them to Europe.

Trillions of bacteria, fungi, and other microbes live in the digestive tract. Many of them are beneficial to human health—influencing our metabolism and immune system, for example. But their diversity is under threat from industrialization, urbanization, and environmental changes. When Muhummed analyzed some of the samples he’d collected—culturing them in petri dishes and adding a dye to make them visible under a microscope—he was astounded to find signs of antibiotic resistance, even in samples taken from children who had never been exposed to modern antibiotics.

That’s one of the reasons scientists want to create a global biobank—a Noah’s ark of microbes, so to speak—and permanently store samples from around the world, before it’s too late. “Of course, it is difficult to concretely say what we are losing,” says microbiologist Adrian Egli, who is based in Zurich and is part of the launch team for the Microbiota Vault project.

Source: https://www.microbiotavault.org/
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https://www.wired.co.uk/

How to Reverse Age-related Brain Deterioration

Research from APC Microbiome Ireland (APCSFI Research Centre at University College Cork (UCC) published in the journal Nature Aging introduces a novel approach to reverse aspects of aging-related deterioration in the brain and cognitive function via the microbes in the gut.

As our population ages one of the key global challenges is to develop strategies to maintain healthy brain function. This ground-breaking research opens up a potentially new therapeutic avenues in the form of microbial-based interventions to slow down brain aging and associated cognitive problems. The work was carried out by researchers in the Brain-Gut-Microbiota lab in APC led by Prof John F. Cryan, Vice President for Research & Innovation, University College Cork as well as a Principal Investigator at APC Microbiome Ireland an SFI Research Centre, based in in University College Cork and Teagasc Moorepark.

There is a growing appreciation of the importance of the microbes in the gut on all aspects of physiology and medicine. In this latest mouse study the authors show that by transplanting microbes from young into old animals they could rejuvenate aspects of brain and immune function.

Prof John F. Cryan, says “Previous research published by the APC and other groups internationally has shown that the gut microbiome plays a key role in aging and the aging process. This new research is a potential game changer , as we have established that the microbiome can be harnessed to reverse age-related brain deterioration. We also see evidence of improved learning ability and cognitive function”.

Although very exciting Cryan cautions that “it is still early days and much more work is needed to see how these findings could be translated in humans”.

APC Director Prof Paul Ross stated that “This research of Prof. Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across the brain/gut axis where brain functioning can be positively influenced. The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health”.

The study was led by co-first authors Dr Marcus Boehme along with PhD student Katherine E. Guzzetta, and Dr Thomaz Bastiaanssen.

Source: https://www.ucc.ie/

Junk food linked to gut inflammation

Eating a Western diet impairs the immune system in the gut in ways that could increase risk of infection and inflammatory bowel disease, according to a study from researchers at Washington University School of Medicine in St. Louis and Cleveland Clinic.

The study, in mice and people, showed that a diet high in sugar and fat causes damage to Paneth cells, immune cells in the gut that help keep inflammation in check. When Paneth cells aren’t functioning properly, the gut immune system is excessively prone to inflammation, putting people at risk of inflammatory bowel disease and undermining effective control of disease-causing microbes. The findings, published in Cell Host & Microbe, open up new approaches to regulating gut immunity by restoring normal Paneth cell function.

A tiny, 3D model of the intestines formed from anti-inflammatory cells known as Paneth cells (green and red) and other intestinal cells (blue) is seen in the image above. Researchers at Washington University School of Medicine in St. Louis and Cleveland Clinic used such models, called organoids, to understand why a Western-style diet rich in fat and sugar damages Paneth cells and disrupts the gut immune system

Inflammatory bowel disease has historically been a problem primarily in Western countries such as the U.S., but it’s becoming more common globally as more and more people adopt Western lifestyles,” said lead author Ta-Chiang Liu, MD, PhD, an associate professor of pathology & immunology at Washington University. “Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections.”

Paneth cell impairment is a key feature of inflammatory bowel disease. For example, people with Crohn’s disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia and fatigue, often have Paneth cells that have stopped working.

Source: https://medicine.wustl.edu/

How To Fine-Tune Bacterial Metabolism To Boost Longevity

Studies have shown that gut microbes can influence several aspects of the host’s life, including aging. Given the complexity and heterogeneity of the human gut environment, elucidating how a specific microbial species contributes to longevity has been challenging.

To explore the influence of bacterial products on the aging process, scientists at Baylor College of Medicine and Rice University developed a method that uses light to directly control gene expression and metabolite production from bacteria residing in the gut of the laboratory worm Caenorhabditis elegans.

The team reports (“Optogenetic control of gut bacterial metabolism to promote longevity”) in eLife that green-light-induced production of colanic acid by resident Escherichia coli bacteria protected gut cells against stress-induced cellular damage and extended the worm’s lifespan. The researchers indicate that this method can be applied to study other bacteria and propose that it also might provide in the future a new way to fine-tune bacterial metabolism in the host gut to deliver health benefits with minimal side effects.

Illustration of bacteria in the intestine.

Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an E. coli strain that secretes colanic acid (CA) under the quantitative control of light,” the investigators wrote.

Using this optogenetically-controlled strain to induce CA production directly in the C. elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host.

“Thus, optogenetics can be used to achieve quantitative and temporal control of [the microbiome] metabolism in order to reveal its local and systemic effects on host health and aging. “We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms,” said co-corresponding author Meng Wang, PhD, professor of molecular and human genetics at the Huffington Center on Aging at Baylor.

Source: https://www.genengnews.com/

Diabetics die 3 times more of Covid-19

From the outset of the pandemic, data coming out of early coronavirus hot spots like China, Italy, and New York City foretold that certain groups of people would be more vulnerable to Covid-19. The disease hit older people and people with underlying medical conditions the hardest. As early as February, diabetes had emerged as one of the conditions associated with the highest risk. In one large study out of China, people with diabetes were more than three times as likely to die of Covid-19 than the overall population.

But that’s not what brought four diabetes experts from Australia and the United Kingdom onto a Zoom call back in April. They were supposed to just be catching up—a virtual tea among friends. But talk soon turned to something strange that they’d been seeing in their own hospitals and hearing about through the grapevine. The weird thing was that people were showing up in Covid-19 wards, after having tested positive for the virus, with lots of sugar in their blood. These were people with no known history of diabetes. But you wouldn’t know it from their lab results.

After that call, the experts reached out to colleagues in other countries to see if they’d seen or heard of similar cases. They had. Acute viral infections of all sorts can stress the body, causing blood sugar levels to rise. So that in itself wasn’t unusual, says Francesco Rubino, a bariatric surgeon and diabetes researcher at King’s College in London, who was on that first Zoom call. “What we were seeing and hearing was a little bit different.”

Doctors around the world had described to him strange situations in which Covid-19 patients were showing symptoms of diabetes that didn’t fit the typical two-flavor manifestation of the disease. In most people with type 1 diabetes, their immune cells suddenly turn traitorous, destroying the cells in the pancreas that produce insulin—the hormone that allows glucose to exit the bloodstream and enter cells. People with type 2 diabetes have a different problem; their body slowly becomes resistant to the insulin it does produce. Rubino and his colleagues were seeing blended features of both types showing up spontaneously in people who’d recently been diagnosed with Covid-19.

That was the first clinical puzzle,” he says. For clues to an explanation, Rubino and his colleagues looked to ACE2, the protein receptor that SARS-CoV-2 uses to invade human cells. It appears in the airways, yes, but also in other organs involved in controlling blood sugar, including the gut. Doctors in China discovered copies of the coronavirus in the poop of their Covid-19 patients. And a meta-analysis found that gastrointestinal symptoms plague one out of 10 Covid-19 sufferers.

In the last few decades, scientists have discovered that the gut is not the passive digestive organ once thought. It actually is a major endocrine player—responsible for producing hormone signals that talk to the pancreas, telling it to make more insulin, and to the brain, ordering it to make its owner stop eating. If the coronavirus is messing with these signals, that could provide a biological basis for why Covid-19 would be associated with different forms of diabetes, including hybrid and previously unknown manifestations of the disease. Rubino is one of a growing number of researchers who think that the relationship between the coronavirus and diabetes is actually a two-way street. Having diabetes doesn’t just tip the odds toward contracting a worse case of Covid-19. In some people, the virus might actually trigger the onset of diabetes, and the potential for a lifetime of having to manage it.

Source: https://www.wired.com/

New Vaccine Brings Revolution In Preventing Chronic Inflammation Related To 60% Of Death

As we learn more and more about health, well-being, and all the factors that affect both, inflammation has become a major player in the conversation. Linked with symptoms ranging from bloating and acne to more serious things like depression and cancer, chronic inflammation, researchers believe, could continue to increase in prevalence. But a new vaccine offers hope for the future of preventing inflammatory diseases.

The vaccine, which is currently for animals, was developed by Institut Cochin in France. Researchers already knew about a connection between inflammation, gut health, and the protein flagellin: Flagellin essentially allows into the rest of the body, resulting in inflammation, and while antibodies exist within that intestinal barrier to help prevent leaky gut, it’s harder to keep all the bacteria contained if your microbiome is out of balance. Researchers hypothesized they could boost the flagellin antibodies within the gut, thereby keeping harmful bacteria from spreading into the body. They administered a flagellin vaccine to mice by injecting it directly into their intestinal lining, spurring the production of the flagellin-fighting antibodies. Chronic inflammation is thought to be related to 60% of deaths worldwide, due to its connection to stroke, diabetes, cancer, and more. This vaccine could be a game-changer if scientists are able to replicate the findings in a version for humans, which researcher Benoît Chassaing says they’re working on.

This vaccine strategy can be envisaged in humans, because such abnormalities of the microbiota have been observed in patients with inflammatory and metabolic diseases. With this in mind, we are currently working on a means of locally administering flagellin to the intestinal mucosa,” he says.

They’re also looking into testing the vaccine on animals that already have chronic inflammatory diseases, to see if it can be used for inflammatory treatment, as opposed to just prevention. But until such a vaccine for humans exists, there are lots of ways to combat inflammation naturally. If you’re still looking for more information, check out the Ultimate Guide to Inflammation class.. When inflammation was induced, the unvaccinated mice became obese, and the vaccinated mice did not. Immunization quelled intestinal inflammation by lowering levels of the flagellin-expressing bacteria in their microbiota, intestines, and intestinal lining.

Source: https://www.mindbodygreen.com/

How To Strengthen Your Immune System

There’s another reason to celebrate the gut microbiome—a healthy gut might actually be able to save lives. According to scientists at the Lawson Health Research Institute, all it takes to strengthen your immune system is to improve your gut health, a process that we know is as easy as increasing your ingestion of probiotics and dietary fiber. How’s that for functional food?

These Lawson Health Research Institute scientists are implementing a preliminary study that would discover whether a fecal transplant of a healthy microbiome can help patients with melanoma become more receptive to immunotherapy treatments. During immunotherapy treatments, patients take certain drugs to stimulate their immune systems in order to attack tumors in their bodies. A fecal transplant, according to these researchers, would make their immune systems more receptive to the drugs and, in turn, could help more people successfully fight their cancer.

We know that some people’s immune systems don’t respond well, and it seems to be associated with the microbes within your gut,” Michael Silverman, M.D., a Lawson associate scientist, said in a video filmed by the research institute. “The goal is to give people healthy microbes to replenish the microbes in their gut so that their immune system responds optimally, and they’re able to control the tumor.”

Source: https://www.mindbodygreen.com/

The Brain In Your Gut

From moods to memory, the brain in our guts has a big impact on the brain in our heads. Pioneering neuroscientist Associate Professor Elisa Hill-Yardin from RMIT in Australia has spent years delving deep into the gut-brain connection, an emerging field in health research. Here she shares the five critical things we should know about our “gut brain”.

The gut has similar types of neurons to the brain. The gut brain is a big nervous system, about the same size as the spinal cord, which controls the contractions of the gut and its secretions. There are very rare gene mutations that affect brain connectivity and we’ve learned that the vast majority of those gene mutations are also found in the gut. If those mutations change the wiring in the brain, they’re also likely to change the wiring and the action of the gut brain – the enteric nervous system. To date, we’ve only ever examined the effect of those mutations in the brain. Now we’re starting to look at them in our second brain, the gut.

We now know that microbes in the gut do change our mood and behaviour, and microbes even change brain activity. There’s a great study that looked at women, doing MRI brain scans and showing that if they ate yoghurt for a certain number of days their resting brain activity was different – which is amazing! But we also know from animal studies that microbes have an impact on mental health. You can breed mice that are germ free and we know that those mice show differences in their anxiety behaviours – in other words, they’re less anxious without the microbes. So you could say we’re being controlled by the microbes in our gut. They’re much more important to our feelings than we ever thought.

What’s come out in research in recent years, though it’s been known for a long time in the autism community, is that the majority of children with autism have serious gut problems. Now we don’t know the cause of autism but we do know that there are hundreds and hundreds of rare gene mutations that alter brain connectivity. And we now know that some of those mutated genes are also found in the gut. We’re also learning that diseases that affect cognition and memory, like dementia, may also have a gut component. Researchers are starting to look at traditional brain diseases like Alzheimer’s, Parkinson’s, Multiple Sclerosis, and finding difference in the microbes in the gut. So they’re starting to think about how we can make changes in our microbes to make changes to our brain health.

The Gut-Brain Axis team that I lead at RMIT is focused on understanding how the enteric nervous system is altered in neurological disorders such as autism. This includes researching how the gut nervous system interacts with microbes in the intestine and changes in inflammatory pathways. We’re trying to identify the basic mechanisms, examining the connections between the gastrointestinal tract and changes in mood and behaviour, including the impact of genetics on microbiota in the gut. The ultimate the aim is to find novel therapies that can improve daily life for people with autism, but our work also has broader application for other neurological disorders, such Parkinson’s disease.

Many of the great enteric physiologist pioneers are in Australia and they were the first to describe different types of neurons based on their activity and neurochemical content. This work has been done on animal models, due to the possibilities of emulating human genetic diseases in these models. So, a lot of basic anatomy and physiology has been studied. But what we need now is to move the field towards using the latest sophisticated techniques and capitalising on the recent interest in the gut-brain axis, which of course involves understanding how the gastrointestinal tract works in concert with the trillions of microbes that live inside it.

Professor Elisa Hill-Yardin has presented her work to the US Air Force Office of Scientific Research

Source: https://www.rmit.edu.au/