Connect with us

GASTROINTESTINAL

Could The Microbiome Of Our Gut, Hold The Secret To Living Longer?

Published

on

You are what you eat. Or so the saying goes. Science now tells us that we are what the bacteria living in our intestinal tract eat and this could have an influence on how well we age. Building on this, McGill University scientists fed fruit flies with a combination of probiotics and an herbal supplement called Triphala that was able to prolong the flies’ longevity by 60 % and protect them against chronic diseases associated with aging.

The study, published in Scientific Reports, adds to a growing body of evidence of the influence that gut bacteria can have on health. The researchers incorporated a symbiotic — made of probiotics with a polyphenol-rich supplement — into the diet of fruit flies.

The flies fed with the synbiotic lived up to 66 days old — 26 days more than the ones without the supplement. They also showed reduced traits of aging, such as mounting insulin resistance, inflammation and oxidative stress.

“Probiotics dramatically change the architecture of the gut microbiota, not only in its composition but also in respect to how the foods that we eat are metabolized,” says Satya Prakash, professor of biomedical engineering in McGill’s Faculty of Medicine and senior author of the study.

“This allows a single probiotic formulation to simultaneously act on several biochemical signaling pathways to elicit broad beneficial physiological effects, and explains why the single formulation we present in this paper has such a dramatic effect on so many different markers.”

The fruit fly is remarkably similar to mammals with about 70 % similarity in terms of their biochemical pathways, making it a good indicator of what would happen in humans, adds Prakash.

“The effects in humans would likely not be as dramatic, but our results definitely suggest that a diet specifically incorporating Triphala along with these probiotics will promote a long and healthy life.”

The authors also say that the findings can be explained by the “gut-brain axis,” a bidirectional communication system between microorganisms residing in the gastrointestinal tract — the microbiota — and the brain. In the past few years, studies have shown the gut-brain axis to be involved in neuropathological changes and a variety of conditions such as irritable bowel syndrome, neurodegeneration and even depression. Few studies, however, have successfully designed gut microbiota-modulating therapeutics having effects as potent or broad as the formulation presented in the new study.

Learning from traditional medicine

The herbal supplement used in the study, Triphala, is a formulation made from amalaki, bibhitaki and haritaki, fruits used as medicinal plants in Ayurveda, a form of traditional Indian medicine.

Susan Westfall, a former PhD student at McGill and lead author of the study, says the idea of combining Triphala and probiotics comes from her long-standing interest in studying natural products derived from traditional Indian medicine and their impact on neurodegenerative diseases.

“At the onset of this study, we were hopeful that combining Triphala with probiotics would be at least a little better than their individual components in terms of physiological benefit, but we did not imagine how successful this formulation would be,” says Westfall, who is now a postdoctoral fellow at the Icahn School of Medicine at Mount Sinai in New York, USA.

The new study, which includes data filed in a US provisional patent through a company cofounded by the authors, has the potential to impact the field of the microbiome, probiotics and human health.

Considering the broad physiological effects of this formulation shown in the fruit fly, Prakash hopes their formulation could have interesting applications in a number of human disorders such as diabetes, obesity, neurodegeneration, chronic inflammation, depression, irritable bowel syndrome and even cancer.

GASTROINTESTINAL

Viruses In Blood Lead To Digestive Problems

Published

on

While studying viruses best known for infecting the brain, researchers at Washington University School of Medicine in St. Louis stumbled upon clues to a conundrum involving a completely different part of the anatomy: the bowel, and why some people possibly develop digestive problems seemingly out of the blue.

The researchers found that viruses such as West Nile and Zika that target the nervous system in the brain and spinal cord also can kill neurons in the guts of mice, disrupting bowel movement and causing intestinal blockages. Other viruses that infect neurons also may cause the same symptoms, the researchers said.

The findings, published Oct. 4 in the journal Cell, potentially could explain why some people experience recurrent, unpredictable bouts of abdominal pain and constipation — and perhaps point to a new strategy for preventing such conditions.

“There are a number of people who are otherwise healthy who suddenly develop bowel motility problems, and we don’t understand why,” said Thaddeus S. Stappenbeck, MD, PhD, the Conan Professor of Laboratory and Genomic Medicine and the study’s co-senior author.

“But now we believe that one explanation could be that you can get a viral infection that results in your immune cells killing infected neurons in your gut. That might be why all of a sudden you can’t move things along any more.”

Postdoctoral researcher and first author James White, PhD, was studying mice infected with West Nile virus, a mosquito-borne virus that causes inflammation in the brain, when he noticed something peculiar. The intestines of some of the infected mice were packed with waste higher up and empty farther down, as if they had a blockage.

“We actually noticed this long ago, but we ignored it because it wasn’t the focus of our research at the time,” said West Nile expert Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and the paper’s co-senior author.

“But Jim White dug in. He wanted to figure out why this was happening.”

White, Diamond, Stappenbeck and colleagues including Robert Hueckeroth, MD, PhD, of the University of Pennsylvania, found that not only West Nile virus but its cousins Zika, Powassan and Kunjin viruses — all of which target the nervous system like West Nile — caused the intestines to expand and slowed down transit through the gut. In contrast, chikungunya virus, an unrelated virus that does not target neurons, failed to cause bowel dysfunction.

Further investigation showed that West Nile virus, when injected into a mouse’s foot, travels through the bloodstream and infects neurons in the intestinal wall. These neurons coordinate muscle contractions to move waste smoothly through the gut. Once infected, the neurons attract the attention of immune cells, which attack the viruses — and kill the neurons in the process.

“Any virus that has a propensity to target neurons could cause this kind of damage,” said Diamond, who is also a professor of molecular microbiology and of pathology and immunology.

“West Nile and related viruses are not very common in the U.S. But there are many other viruses that are more widespread, such as enteroviruses and herpesviruses, that also may be able to target specific neurons in the wall of the intestine and injure them.”

If that’s the case, such widespread viruses may provide a new target in the prevention or treatment of painful digestive issues. Having chronic gut motility problems is a miserable experience, and while the condition can be managed, it can’t be cured or prevented.

“Many of the viruses that might target the gut nervous system cause mild, self-limiting infections, and there’s never been reason to develop a vaccine for them,” Diamond said.

“But if you knew that some particular viruses were causing this serious and common problem, you might be more apt to try to develop a vaccine.”

The infected mice’s digestive tracts gradually recovered over an eight-week time span. But when the researchers challenged the mice with an unrelated virus or an immune stimulant, the bowel problems promptly returned. This pattern echoed the one seen in people, who cycle through bouts of gastrointestinal distress and recovery. The flare-ups often are triggered by stress or illness, but they also can occur for no apparent reason.

“It’s amazing that the nervous system of the gut is able to recover and re-establish near normal motility, even after taking a pretty big hit and losing a lot of cells,” said Stappenbeck, who is also a professor of developmental biology.

“But then, it’s really just barely functioning normally, and when you add any stress, it malfunctions again.”

Previous studies have linked bowel motility to changes in the microbiome – the community of bacteria, viruses and fungi that live in the gut.

“What we need to explore now is how this story connects to everything else we know about gut motility,” Stappenbeck said.

“What effect does damage to the gut nervous system have on the microbiome? We would love to connect those dots.”

Continue Reading

GASTROINTESTINAL

Ingestible ‘Bacteria On A Chip’ Could Help Diagnose Disease

Published

on

MIT researchers have built an ingestible sensor equipped with genetically engineered bacteria that can diagnose bleeding in the stomach or other gastrointestinal problems.

This “bacteria-on-a-chip” approach combines sensors made from living cells with ultra-low-power electronics that convert the bacterial response into a wireless signal that can be read by a smartphone.

“By combining engineered biological sensors together with low-power wireless electronics, we can detect biological signals in the body and in near real-time, enabling new diagnostic capabilities for human health applications,” says Timothy Lu, an MIT associate professor of electrical engineering and computer science and of biological engineering.

In the new study, appearing in the May 24 online edition of Science, the researchers created sensors that respond to heme, a component of blood, and showed that they work in pigs. They also designed sensors that can respond to a molecule that is a marker of inflammation.

Lu and Anantha Chandrakasan, dean of MIT’s School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science, are the senior authors of the study. The lead authors are graduate student Mark Mimee and former MIT postdoc Phillip Nadeau.

Wireless communication

In the past decade, synthetic biologists have made great strides in engineering bacteria to respond to stimuli such as environmental pollutants or markers of disease. These bacteria can be designed to produce outputs such as light when they detect the target stimulus, but specialized lab equipment is usually required to measure this response.

To make these bacteria more useful for real-world applications, the MIT team decided to combine them with an electronic chip that could translate the bacterial response into a wireless signal.

“Our idea was to package bacterial cells inside a device,” Nadeau says. “The cells would be trapped and go along for the ride as the device passes through the stomach.”

For their initial demonstration, the researchers focused on bleeding in the GI tract. They engineered a probiotic strain of E. coli to express a genetic circuit that causes the bacteria to emit light when they encounter heme.

They placed the bacteria into four wells on their custom-designed sensor, covered by a semipermeable membrane that allows small molecules from the surrounding environment to diffuse through. Underneath each well is a phototransistor that can measure the amount of light produced by the bacterial cells and relay the information to a microprocessor that sends a wireless signal to a nearby computer or smartphone. The researchers also built an Android app that can be used to analyze the data.

The sensor, which is a cylinder about 1.5 inches long, requires about 13 microwatts of power. The researchers equipped the sensor with a 2.7-volt battery, which they estimate could power the device for about 1.5 months of continuous use. They say it could also be powered by a voltaic cell sustained by acidic fluids in the stomach, using technology that Nadeau and Chandrakasan have previously developed.

“The focus of this work is on system design and integration to combine the power of bacterial sensing with ultra-low-power circuits to realize important health sensing applications,” Chandrakasan says.

Diagnosing disease

The researchers tested the ingestible sensor in pigs and showed that it could correctly determine whether any blood was present in the stomach. They anticipate that this type of sensor could be either deployed for one-time use or designed to remain the digestive tract for several days or weeks, sending continuous signals.

Currently, if patients are suspected to be bleeding from a gastric ulcer, they have to undergo an endoscopy to diagnose the problem, which often requires the patient to be sedated.

“The goal with this sensor is that you would be able to circumvent an unnecessary procedure by just ingesting the capsule, and within a relatively short period of time you would know whether or not there was a bleeding event,” Mimee says.

To help move the technology toward patient use, the researchers plan to reduce the size of the sensor and to study how long the bacteria cells can survive in the digestive tract. They also hope to develop sensors for gastrointestinal conditions other than bleeding.

In the Science paper, the researchers adapted previously described sensors for two other molecules, which they have not yet tested in animals. One of the sensors detects a sulfur-containing ion called thiosulfate, which is linked to inflammation and could be used to monitor patients with Crohn’s disease or other inflammatory conditions. The other detects a bacterial signaling molecule called AHL, which can serve as a marker for gastrointestinal infections because different types of bacteria produce slightly different versions of the molecule.

“Most of the work we did in the paper was related to blood, but conceivably you could engineer bacteria to sense anything and produce light in response to that,” Mimee says. “Anyone who is trying to engineer bacteria to sense a molecule related to disease could slot it into one of those wells, and it would be ready to go.”

The researchers say the sensors could also be designed to carry multiple strains of bacteria, allowing them to diagnose a variety of conditions.

“Right now, we have four detection sites, but if you could extend it to 16 or 256, then you could have multiple different types of cells and be able to read them all out in parallel, enabling more high-throughput screening,” Nadeau says.

Continue Reading

GASTROINTESTINAL

Fasting Boosts Stem Cells’ Regenerative Capacity

Published

on

As people age, their intestinal stem cells begin to lose their ability to regenerate. These stem cells are the source for all new intestinal cells, so this decline can make it more difficult to recover from gastrointestinal infections or other conditions that affect the intestine.

This age-related loss of stem cell function can be reversed by a 24-hour fast, according to a new study from MIT biologists. The researchers found that fasting dramatically improves stem cells’ ability to regenerate, in both aged and young mice.

In fasting mice, cells begin breaking down fatty acids instead of glucose, a change that stimulates the stem cells to become more regenerative. The researchers found that they could also boost regeneration with a molecule that activates the same metabolic switch. Such an intervention could potentially help older people recovering from GI infections or cancer patients undergoing chemotherapy, the researchers say.

“Fasting has many effects in the intestine, which include boosting regeneration as well as potential uses in any type of ailment that impinges on the intestine, such as infections or cancers,” says Omer Yilmaz, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. “Understanding how fasting improves overall health, including the role of adult stem cells in intestinal regeneration, in repair, and in aging, is a fundamental interest of my laboratory.”

David Sabatini, an MIT professor of biology and member of the Whitehead Institute for Biomedical Research, is also a senior author of the paper, which appears in the May 3 issue of Cell Stem Cell.

“This study provided evidence that fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat,” Sabatini says. “Interestingly, switching these cells to fatty acid oxidation enhanced their function significantly. Pharmacological targeting of this pathway may provide a therapeutic opportunity to improve tissue homeostasis in age-associated pathologies.”

The paper’s lead authors are Whitehead Institute postdoc Maria Mihaylova and Koch Institute postdoc Chia-Wei Cheng.

Boosting regeneration

For many decades, scientists have known that low caloric intake is linked with enhanced longevity in humans and other organisms. Yilmaz and his colleagues were interested in exploring how fasting exerts its effects at the molecular level, specifically in the intestine.

Intestinal stem cells are responsible for maintaining the lining of the intestine, which typically renews itself every five days. When an injury or infection occurs, stem cells are key to repairing any damage. As people age, the regenerative abilities of these intestinal stem cells decline, so it takes longer for the intestine to recover.

“Intestinal stem cells are the workhorses of the intestine that give rise to more stem cells and to all of the various differentiated cell types of the intestine. Notably, during aging, intestinal stem function declines, which impairs the ability of the intestine to repair itself after damage,” Yilmaz says. “In this line of investigation, we focused on understanding how a 24-hour fast enhances the function of young and old intestinal stem cells.”

After mice fasted for 24 hours, the researchers removed intestinal stem cells and grew them in a culture dish, allowing them to determine whether the cells can give rise to “mini-intestines” known as organoids.

The researchers found that stem cells from the fasting mice doubled their regenerative capacity.

“It was very obvious that fasting had this really immense effect on the ability of intestinal crypts to form more organoids, which is stem-cell-driven,” Mihaylova says. “This was something that we saw in both the young mice and the aged mice, and we really wanted to understand the molecular mechanisms driving this.”

Metabolic switch

Further studies, including sequencing the messenger RNA of stem cells from the mice that fasted, revealed that fasting induces cells to switch from their usual metabolism, which burns carbohydrates such as sugars, to metabolizing fatty acids. This switch occurs through the activation of transcription factors called PPARs, which turn on many genes that are involved in metabolizing fatty acids.

The researchers found that if they turned off this pathway, fasting could no longer boost regeneration. They now plan to study how this metabolic switch provokes stem cells to enhance their regenerative abilities.

They also found that they could reproduce the beneficial effects of fasting by treating mice with a molecule that mimics the effects of PPARs. “That was also very surprising,” Cheng says. “Just activating one metabolic pathway is sufficient to reverse certain age phenotypes.”

The findings suggest that drug treatment could stimulate regeneration without requiring patients to fast, which is difficult for most people. One group that could benefit from such treatment is cancer patients who are receiving chemotherapy, which often harms intestinal cells. It could also benefit older people who experience intestinal infections or other gastrointestinal disorders that can damage the lining of the intestine.

The researchers plan to explore the potential effectiveness of such treatments, and they also hope to study whether fasting affects regenerative abilities in stem cells in other types of tissue.

Continue Reading

Like Us on Facebook

Trending Posts

News1 day ago

Paternal Transmission Of Epigenetic Memory Via Sperm

Studies of human populations and animal models suggest that a father’s experiences such as diet or environmental stress can influence...

News1 day ago

Father’s Nicotine Use Can Cause Cognitive Problems In Children And Grandchildren

A father’s exposure to nicotine may cause cognitive deficits in his children and even grandchildren, according to a study in...

News1 day ago

Nutrition Has A Greater Impact On Bone Strength Than Exercise

ANN ARBOR—One question that scientists and fitness experts alike would love to answer is whether exercise or nutrition has a...

News2 days ago

Breast­feed­ing Pro­tects In­fants From An­ti­bi­otic-Res­ist­ant Bac­teria

Globally, more than 200,000 newborns die annually of infections caused by antibiotic-resistant bacteria. However, a new study shows that breastfeeding...

News2 days ago

Combining Genetic and Sun Exposure Data Improves Skin Cancer Risk

SAN DIEGO, Calif. – By combining data on individuals’ lifetime sun exposure and their genetics, researchers can generate improved predictions...

News3 days ago

More Clues Revealed In Link Between Normal Breast Changes And Invasive Breast Cancer

A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process —...

News3 days ago

Kids’ Sleep May Suffer From Moms’ Tight Work Schedules

It may be tough for working moms to get a good night’s sleep, but working tight hours may affect their...

Trending