Gut Bacteria

Vitamin D Boosts Gut Bacteria for Cancer Immunity

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Summary: Vitamin D enhances a type of gut bacteria in mice, improving their immunity to cancer. The study shows that mice with higher levels of vitamin D resist tumor growth better and respond more effectively to immunotherapy.

This effect seems linked to the increase of Bacteroides fragilis in the gut, which somehow enhances the mice’s immune response to cancer. Further research is needed to see if this applies to humans, as earlier studies suggest a potential link between vitamin D levels and cancer risk.

Key Facts:

  1. Vitamin D Role: Mice fed with vitamin D exhibited increased levels of Bacteroides fragilis, which helped them resist cancer better.
  2. Human Implications: Preliminary data analysis from 1.5 million people in Denmark hints at a correlation between low vitamin D levels and higher cancer risk.
  3. Future Research: Understanding how vitamin D can be utilized to boost the beneficial gut microbiome could open new pathways for cancer treatment and prevention.

Source: Francis Crick Institute

Researchers at the Francis Crick Institute, the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH) and Aalborg University in Denmark, have found that vitamin D encourages the growth of a type of gut bacteria in mice which improves immunity to cancer.

Reported today in Science, the researchers found that mice given a diet rich in vitamin D had better immune resistance to experimentally transplanted cancers and improved responses to immunotherapy treatment.

This effect was also seen when gene editing was used to remove a protein that binds to vitamin D in the blood and keeps it away from tissues.

Surprisingly, the team found that vitamin D acts on epithelial cells in the intestine, which in turn increase the amount of a bacteria called Bacteroides fragilis. This microbe gave mice better immunity to cancer as the transplanted tumours didn’t grow as much, but the researchers are not yet sure how.

To test if the bacteria alone could give better cancer immunity, mice on a normal diet were given Bacteroides fragilis. These mice were also better able to resist tumour growth but not when the mice were placed on a vitamin D-deficient diet.

Previous studies have proposed a link between vitamin D deficiency and cancer risk in humans, although the evidence hasn’t been conclusive.

To investigate this, the researchers analysed a dataset from 1.5 million people in Denmark, which highlighted a link between lower vitamin D levels and a higher risk of cancer.

A separate analysis of a cancer patient population also suggested that people with higher vitamin D levels were more likely to respond well to immune-based cancer treatments.

Although Bacteroides fragilis is also found in the microbiome in humans, more research is needed to understand whether vitamin D helps provide some immune resistance to cancer through the same mechanism.

Caetano Reis e Sousa, head of the Immunobiology Laboratory at the Crick, and senior author, said: “What we’ve shown here came as a surprise – vitamin D can regulate the gut microbiome to favour a type of bacteria which gives mice better immunity to cancer.

“This could one day be important for cancer treatment in humans, but we don’t know how and why vitamin D has this effect via the microbiome. More work is needed before we can conclusively say that correcting a vitamin D deficiency has benefits for cancer prevention or treatment.”

Evangelos Giampazolias, former postdoctoral researcher at the Crick, and now Group Leader of the Cancer Immunosurveillance Group at the Cancer Research UK Manchester Institute, said: “Pinpointing the factors that distinguish a ‘good’ from a ‘bad’ microbiome is a major challenge. We found that vitamin D helps gut bacteria to elicit cancer immunity improving the response to immunotherapy in mice.

“A key question we are currently trying to answer is how exactly vitamin D supports a ‘good’ microbiome. If we can answer this, we might uncover new ways in which the microbiome influences the immune system, potentially offering exciting possibilities in preventing or treating cancer.”

Romina Goldszmid, Stadtman Investigator in NCI’s Center For Cancer Research, said: “These findings contribute to the growing body of knowledge on the role of microbiota in cancer immunity and the potential of dietary interventions to fine-tune this relationship for improved patient outcomes.

“However, further research is warranted to fully understand the underlying mechanisms and how they can be harnessed to develop personalized treatment strategies.”

This research was funded by Cancer Research UK, the UK Medical Research Council, the Wellcome Trust, an ERC Advanced Investigator grant, a Wellcome Investigator Award, a prize from the Louis-Jeantet Foundation, the Intramural Research Program of the NCI, part of the National Institutes of Health, CCR-NCI and the Danish National Research Foundation.

Research Information Manager at Cancer Research UK, Dr Nisharnthi Duggan said: “We know that vitamin D deficiency can cause health problems, however, there isn’t enough evidence to link vitamin D levels to cancer risk.

This early-stage research in mice, coupled with an analysis of Danish population data, seeks to address the evidence gap. While the findings suggest a possible link between vitamin D and immune responses to cancer, further research is needed to confirm this.

“A bit of sunlight can help our bodies make vitamin D but you don’t need to sunbathe to boost this process. Most people in the UK can make enough vitamin D by spending short periods of time in the summer sun.

“We can also get vitamin D from our diet and supplements. We know that staying safe in the sun can reduce the risk of cancer, so make sure to seek shade, cover up and apply sunscreen when the sun is strong.”

Abstract

Vitamin D regulates microbiome-dependent cancer immunity

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies.

Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival.

In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity.

Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer.

Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

New Study Shows How Gut Bacteria Break Down Cholesterol

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Ongoing research reveals synergistic effects of gut bacteria working to clear cholesterol. Higher levels of bacteria are associated with lower cholesterol. 

New research highlights species of healthy gut bacteria that play a key role in helping regulate cholesterol levels.

Published April 2 in Cell, the study identified that specific bacteria in the genus Oscillibacter consume cholesterol, and that people with higher levels of Oscillibacter in their guts had corresponding lower levels of cholesterol. The findings come from among more than 1,400 samples examined as part of the long-term Framingham Heart study aimed at lowering the damage from cardiovascular disease.

Stool samples are often used to determine the microbial composition of the gut microbiome, which is made up of bacteria and other microorganisms like viruses and fungi.

The research team’s goal was to identify how the gut might play a role in lowering the risk of heart disease, the top killer in the United States. One in every five deaths—about 695,000 people—was from cardiovascular disease in 2021, according to the U.S. Centers for Disease Control and Prevention.

Unraveling Microscopic Mysteries

The research involved collecting a library of stool samples over many years and then sorting through more than 16,000 relationships between microbes and their metabolic traits. Scientists noted the strongest association discovered was Oscillibacter levels appearing to be protective of cholesterol levels.

Cholesterol and other substances create plaque—a condition called atherosclerosis—that can build up in the arteries blocking blood flow and potentially lead to heart disease, stroke, heart attack, and blood clots.

Further tests involving growing the bacteria to study metabolic pathways revealed that bacteria converted cholesterol into other products before it was broken down by other bacteria and then excreted. Researchers were assisted by machine learning to determine that Oscillibacter were responsible for creating that biochemical conversion, according to a news release published by the Broad Institute of MIT and Harvard.

Harvard Scientist Stunned: Oreos Surpass Statins in Lowering His Cholesterol

Researchers also found another bacterial species previously discovered to contribute to lowering cholesterol, Eubacterium coprostanoligenes, may have a synergistic effect with Oscillibacter in metabolizing cholesterol.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Dr. Ramnik Xavier, co-director of the infectious disease and microbiome program at Broad, in the news release. He is a professor at Harvard Medical School and chief of gastroenterology at Massachusetts General Hospital.

Expanding Understanding

According to a Harvard Medical School article, scientists have known for a century that gut bacteria break down cholesterol into coprostanol, though they didn’t understand the mechanism or species involved.

An earlier study from the team published in 2020 in Cell Host and Microbe looked at 3,097 stool samples and found that people who had a particular gene in their microbiome—called IsmA—had less cholesterol in their stool, as well as lower blood cholesterol levels. The gene, they determined, made an enzyme to metabolize cholesterol, explaining how some people can eat diets higher in cholesterol but don’t impact their blood cholesterol levels.

“The findings lend more support to the concept that modifying the microbiome could have a therapeutic effect,” study co-author Dr. Stanley Shaw said in the article. A cardiologist at Brigham and Women’s Hospital and associate dean for executive education at Harvard Medical School, Dr. Shaw noted that microbiome-based therapy for heart disease will take years to develop.

Microbiome Therapeutics Coming … Someday

Therapies could mean specific enzyme therapy, probiotics, diet, or other methods. Probiotics can be found in foods like yogurt and fermented vegetables—or in supplements.

The latest study reiterates that the work could ultimately point them to a method for manipulating the microbiome in order to decrease cholesterol levels.

“Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host,” postdoctoral researcher Chenhao Li, a co-first author of the study, added.

Is More Medical Intervention Better?

Though the researchers may be well-intentioned, Dr. Craig Backs told The Epoch Times that strictly honing in on bacteria is overly simplified, has gaps that ignore underlying issues, and leads to a “pill for an ill” approach already dominating medicine.

“There’s clearly more to it than, ‘Fix your cholesterol, and you’ll have less heart disease,’” he said, noting that cholesterol is also one of several risk factors that include smoking, obesity, diet, diabetes, and high blood pressure.

He added, “You can talk about the microbiome all you want, but the way to support the microbiome is to feed the microbiome whole foods.”

Dr. Backs, an internist and founder of the Cure Center for Chronic Disease, coaches his patients to eat more healthily, including staying away from sugar, which also increases cholesterol and wreaks havoc on cardiometabolism.

His intent is to help patients understand why their cholesterol is elevated in the first place and reduce reliance on medication. The Mayo Clinic states that high cholesterol can be the result of inactivity, an unhealthy diet, and even some medications. Genetics can play a role, but it’s overstated.

“If your cholesterol is high, odds are you got it the old-fashioned way through a questionable diet, a lack of exercise and the process of aging,” interventional cardiologist Dr. Leslie Cho said in a Cleveland Clinic article.

Circling Back to the Microbiome

Those lifestyle factors are also linked to dysbiosis—an imbalance of gut microbes that causes the populations of good bacteria to decrease. In fact, lower levels of Oscillibacter bacteria have been associated with obesity.

Oscillibacter metabolizes to create the short-chain fatty acid butyrate. Among its roles in the human body, butyrate helps ameliorate oxidative status. Left unchecked, oxidation in the body can create a kind of inflammatory response that allows for plaque buildup.

With trillions of bacteria living in the human gut—including some not yet identified—associations are a complex medical mystery scientists are still unraveling. But the relationship between functional foods and the cholesterol-lowering mechanisms of the gut microbiota warrant significant study, notes a 2023 study in Foods.

“Gut microbiota dysbiosis is a risk factor in the pathophysiological processes related to cholesterol-associated diseases, constituting a subtle and potential mechanism of disease onset,” the study concludes. “Furthermore, the interaction between natural functional [food] ingredients and the cholesterol-lowering actions of the gut microbiota also represents a significant focus of research.

“This focus is poised to profoundly impact the development of novel therapeutic strategies for drug treatment.”

Gut bacteria and the immune system: How aging changes the microbiome and can lead to ‘inflammaging’

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The human immune system changes with age. Immune responses start to become less robust as people get older, which makes them more vulnerable to certain infections and diseases. However, immune system aging looks different from person to person. Research has shown that changes to the composition and diversity of the microorganisms in the gut may explain these differences in immune system aging.

The gut microbiome — the population of microorganisms that lives in the gastrointestinal tract — helps the body maintain a stable internal environment when it is faced with external changes. This is known as homeostasis. The gut microbiome supports homeostasis in different ways, such as through helping to keep the immune system alert, and digesting dietary fibre into short-chain fatty acids to strengthen the intestinal wall.

The gut microbiome also helps us to regulate our inflammatory reactions. Inflammation helps the body fight microorganisms that cause disease, and helps repair damaged tissues. However, as the composition of our gut microbiome changes with age, a low level of inflammation can become constant throughout the body. This is called inflammaging.

When inflammaging develops in the gut, it leads to a decrease in immune responses, which puts people at a higher risk for infection and disease.

Let’s take a closer look at the gut microbiome and how it changes with age.

Gut microbiome imbalances in older adults

Diagram of microbial phyla
An overview of the four major gut microbial phyla. (Flore Van Leemput and Narveen Jandu), Author provided (no reuse)

Our gastrointestinal tract can be compared to a densely populated city inhabited by a variety of different bacteria, fungi, archaea and viruses collectively called the gut microbiota. In fact, compared to other parts of the body, the gut microbiome has the largest number of bacteria. In a healthy gut microbiome, there are four dominant families (or phyla) of microorganisms, including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria.

Firmicutes and Bacteroidetes make up around 80 to 90 per cent of the gut microbiota in the digestive tract. Firmicutes help with the production of short-chain fatty acids to support intestinal health and the secretion of mucus to improve intestinal wall defence. Bacteroidetes metabolize complex carbohydrates into vitamins and nutrients, and help promote glycogen storage to improve glucose metabolism.

The gut microbiome and immune system work closely together. The microorganisms in the gut send out signals that are detected by immune sensors. This allows the immune system to regulate the beneficial bacteria in the gut, helping maintain immune homeostasis. Through this interaction, the adaptive immune system also receives stimuli from harmful substances called antigens, which trigger an immune reaction.

However, as people age, the composition and balance of microorganisms in the gut changes. This gives rise to microbial dysbiosis, which means there is a reduction in the number of beneficial bacteria in the gut, alongside a higher number and pro-inflammatory organisms and bacteria that can cause disease. In addition to this, research has also shown that the general diversity of bacteria in our gut also decreases with age.

Over time, the shortage of beneficial bacteria such as Firmicutes in older adults starts to compromise the integrity of their intestinal barrier, causing it to become leaky. This is because the Firmicutes family plays a very important role in keeping the intestinal wall healthy and strong by producing a short-chain fatty acid called butyrate. Short-chain fatty acids such as butyrate help provide nutrients to strengthen the intestinal wall, inform immune responses and lower inflammation.

When intact, the intestinal barrier works to prevent harmful bacteria from passing through the intestinal wall, entering the circulatory system and reaching important organs. However, when there are not enough gut bacteria to produce the short-chain fatty acids that are needed for the intestinal wall to function, bacteria are able to enter the bloodstream. This contributes to the formation of intestinal inflammaging, which refers to a low level of inflammation that becomes steady throughout the body with age.

How inflammaging works

Inflammaging creates an environment that is prone to inflammation, which is caused and maintained by several factors. These can include microorganism imbalances in the intestines (microbial dysbiosis), psychological stress, physical inactivity, poor nutrition and chronic infections.

When the body is exposed to these factors on a regular basis, cellular senescence occurs. Cellular senescence is a state in which cell growth is permanently arrested, which means that cells are no longer able to self-renew. Eventually, this leads to a decrease in immune responses, which are important to prevent foreign substances and pathogens from entering the body.

Diagram of interaction between human gut and microbiota
The microbiome and the human gut work together to maintain health, depicted as a handshake. The green arrows of the inner cycle represent a positive cycle, providing protection to the human gut and allowing it to provide the gut bacteria with a favourable habitat. The red arrows of the outer cycle represent a negative cycle that leads to dysbiosis and reduced immunity. (Flore Van Leemput and Narveen Jandu), Author provided (no reuse)

Maintaining a healthy balance of gut microbiota

There is a common saying that claims “you are what you eat.” Indeed, nutrition and diet play an important role in regulating the number of different microorganisms that live in the gut. This means that diet may also play a key role in the immune function of older adults.

The Mediterranean diet, known for its lower intake of refined carbohydrates, saturated fats, dairy products and red meat, has been shown to have a positive effect on the balance of microorganisms in the gut and the strength of the intestinal barrier. The Mediterranean diet has also been linked to a lower risk of Type 2 diabetes in older adults, allowing these individuals to live a longer and healthier life.

The use of probiotics and prebiotics can also help fight age-related inflammation. Probiotics, such as Lactobacilli and Bifidobacteria, are live microorganisms that can be consumed to support overall health. More specifically, probiotics help improve the function of the intestinal barrier and regulate immune responses by modifying the composition of the gut microbiome. However, there is still some debate around whether the acidic conditions in the stomach allow probiotics to survive long enough to be able to move into the intestine.

It is clear that the immune system has an intricate relationship with the gut microbiome. A healthy and well-balanced gut microbiome will strengthen the intestinal barrier, which helps to reduce inflammation throughout the body and support the immune system.

To achieve this, it is important to maintain a healthy and well-balanced lifestyle as we grow older. This can include lower intake of dairy products and red meats, and harnessing the benefits of probiotics and prebiotics.

New Study Shows How Gut Bacteria Break Down Cholesterol

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Ongoing research reveals synergistic effects of gut bacteria working to clear cholesterol. Higher levels of bacteria are associated with lower cholesterol. 

New Study Shows How Gut Bacteria Break Down Cholesterol

New research highlights species of healthy gut bacteria that play a key role in helping regulate cholesterol levels.

Published April 2 in Cell, the study identified that specific bacteria in the genus Oscillibacter consume cholesterol, and that people with higher levels of Oscillibacter in their guts had corresponding lower levels of cholesterol. The findings come from among more than 1,400 samples examined as part of the long-term Framingham Heart study aimed at lowering the damage from cardiovascular disease.

Stool samples are often used to determine the microbial composition of the gut microbiome, which is made up of bacteria and other microorganisms like viruses and fungi.

The research team’s goal was to identify how the gut might play a role in lowering the risk of heart disease, the top killer in the United States. One in every five deaths—about 695,000 people—was from cardiovascular disease in 2021, according to the U.S. Centers for Disease Control and Prevention.

Unraveling Microscopic Mysteries

The research involved collecting a library of stool samples over many years and then sorting through more than 16,000 relationships between microbes and their metabolic traits. Scientists noted the strongest association discovered was Oscillibacter levels appearing to be protective of cholesterol levels.

Cholesterol and other substances create plaque—a condition called atherosclerosis—that can build up in the arteries blocking blood flow and potentially lead to heart disease, stroke, heart attack, and blood clots.

Further tests involving growing the bacteria to study metabolic pathways revealed that bacteria converted cholesterol into other products before it was broken down by other bacteria and then excreted. Researchers were assisted by machine learning to determine that Oscillibacter were responsible for creating that biochemical conversion, according to a news release published by the Broad Institute of MIT and Harvard

Researchers also found another bacterial species previously discovered to contribute to lowering cholesterol, Eubacterium coprostanoligenes, may have a synergistic effect with Oscillibacter in metabolizing cholesterol.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Dr. Ramnik Xavier, co-director of the infectious disease and microbiome program at Broad, in the news release. He is a professor at Harvard Medical School and chief of gastroenterology at Massachusetts General Hospital.

Expanding Understanding

According to a Harvard Medical School article, scientists have known for a century that gut bacteria break down cholesterol into coprostanol, though they didn’t understand the mechanism or species involved.

An earlier study from the team published in 2020 in Cell Host and Microbe looked at 3,097 stool samples and found that people who had a particular gene in their microbiome—called IsmA—had less cholesterol in their stool, as well as lower blood cholesterol levels. The gene, they determined, made an enzyme to metabolize cholesterol, explaining how some people can eat diets higher in cholesterol but don’t impact their blood cholesterol levels.

“The findings lend more support to the concept that modifying the microbiome could have a therapeutic effect,” study co-author Dr. Stanley Shaw said in the article. A cardiologist at Brigham and Women’s Hospital and associate dean for executive education at Harvard Medical School, Dr. Shaw noted that microbiome-based therapy for heart disease will take years to develop.

Microbiome Therapeutics Coming … Someday

Therapies could mean specific enzyme therapy, probiotics, diet, or other methods. Probiotics can be found in foods like yogurt and fermented vegetables—or in supplements.

The latest study reiterates that the work could ultimately point them to a method for manipulating the microbiome in order to decrease cholesterol levels.

“Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host,” postdoctoral researcher Chenhao Li, a co-first author of the study, added.

Is More Medical Intervention Better?

Though the researchers may be well-intentioned, Dr. Craig Backs told The Epoch Times that strictly honing in on bacteria is overly simplified, has gaps that ignore underlying issues, and leads to a “pill for an ill” approach already dominating medicine.

“There’s clearly more to it than, ‘Fix your cholesterol, and you’ll have less heart disease,’” he said, noting that cholesterol is also one of several risk factors that include smoking, obesity, diet, diabetes, and high blood pressure.

He added, “You can talk about the microbiome all you want, but the way to support the microbiome is to feed the microbiome whole foods.”

Dr. Backs, an internist and founder of the Cure Center for Chronic Disease, coaches his patients to eat more healthily, including staying away from sugar, which also increases cholesterol and wreaks havoc on cardiometabolism.

His intent is to help patients understand why their cholesterol is elevated in the first place and reduce reliance on medication. The Mayo Clinic states that high cholesterol can be the result of inactivity, an unhealthy diet, and even some medications. Genetics can play a role, but it’s overstated.

“If your cholesterol is high, odds are you got it the old-fashioned way through a questionable diet, a lack of exercise and the process of aging,” interventional cardiologist Dr. Leslie Cho said in a Cleveland Clinic article.

Circling Back to the Microbiome

Those lifestyle factors are also linked to dysbiosis—an imbalance of gut microbes that causes the populations of good bacteria to decrease. In fact, lower levels of Oscillibacter bacteria have been associated with obesity.

Oscillibacter metabolizes to create the short-chain fatty acid butyrate. Among its roles in the human body, butyrate helps ameliorate oxidative status. Left unchecked, oxidation in the body can create a kind of inflammatory response that allows for plaque buildup.

With trillions of bacteria living in the human gut—including some not yet identified—associations are a complex medical mystery scientists are still unraveling. But the relationship between functional foods and the cholesterol-lowering mechanisms of the gut microbiota warrant significant study, notes a 2023 study in Foods.

“Gut microbiota dysbiosis is a risk factor in the pathophysiological processes related to cholesterol-associated diseases, constituting a subtle and potential mechanism of disease onset,” the study concludes. “Furthermore, the interaction between natural functional [food] ingredients and the cholesterol-lowering actions of the gut microbiota also represents a significant focus of research.

“This focus is poised to profoundly impact the development of novel therapeutic strategies for drug treatment.”

Certain type of gut bacteria may help lower risk of cardiac disease.

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A collage of a photo of a man against a backdrop of gut bacteria under a microscope
Scientists have linked specific gut bacteria to reduced heart disease risk.
  • Scientists have discovered that gut microbes play a significant role in influencing cardiovascular disease.
  • This builds upon previous research linking the gut microbiota to various health issues like diabetes and obesity.
  • Using data from the Framingham Heart Study, researchers identified specific bacteria in the gut that can break down cholesterol, suggesting a potential path to reducing heart disease risk.
  • This research not only sheds light on the mechanisms by which gut bacteria affect cholesterol levels but also opens the door for treatments aimed at modifying the gut microbiota to improve heart health.

Alterations in the gut microbiota have been linked to several illnessesTrusted Source, such as type 2 diabetes, obesity, and inflammatory bowel disease.

Researchers from the Broad Institute of MIT and Harvard in collaboration with Massachusetts General Hospital have recently discovered that gut microbes could also influence cardiovascular disease.

The new study, published in CellTrusted Source, highlights particular bacterial species in the gut that digest cholesterol, potentially reducing cholesterol levels and the risk of heart disease in individuals.

The researchers examined metabolites and microbial genomes from over 1,400 participants in the long-running Framingham Heart StudyTrusted Source, which investigates cardiovascular disease risk factors.

They found that a type of bacteria called Oscillibacter absorbs and processes cholesterol from its environment, noting that individuals with higher quantities of this microbe in their intestines exhibited reduced cholesterol levels.

The team also uncovered the process these bacteria likely employ to degrade cholesterol.

The findings imply that future interventions targeting the microbiota in specific manners may aid in lowering cholesterol levels in humans.

These discoveries provide a foundation for more focused research on the impact of microbiome alterations on health and disease.

Gut microbiota affects cardiovascular disease risk

Over the last decade, researchers have found associations between the makeup of the gut microbiota and aspects of cardiovascular disease, like levels of triglyceridesTrusted Source and blood sugar after eatingTrusted Source.

However, the development of treatments targeting these links has been challenging, mainly because of an incomplete understanding of the metabolic processes in the gut.

Now, researchers from the Broad Institute achieved a more thorough and detailed view of how gut microbes affect metabolism.

They used a powerful method called shotgun metagenomic sequencing to take a close look at all the DNA of the microorganisms within a sample.

Along with this, they applied a technique called metabolomics to measure the amounts of hundreds of known and even thousands of yet-to-be-identified substances produced by these organisms.

Oscillibacter in the gut may help lower cholesterol levels

The method revealed over 16,000 links between microbes and metabolic characteristics, with one particularly notable finding: individuals hosting several species of bacteria from the Oscillibacter genus exhibited lower cholesterol levels compared to those without these bacteria.

Remarkably, Oscillibacter species were found to be quite prevalent in the gut, averaging about one in every 100 bacteria.

To understand how these microbes metabolize cholesterol, the researchers aimed to identify the biochemical pathway involved, which involved cultivating the organism in a laboratory setting.

Luckily, the laboratory had devoted years to collecting bacteria from stool samples, building a unique collection that includes Oscillibacter species.

After the researchers successfully cultivated the bacteria in the lab, they used mass spectrometry to pinpoint the likely byproducts created when the bacteria process cholesterol.

This helped them understand the methods these bacteria use to reduce cholesterol levels.

They discovered that the bacteria transform cholesterol into substances that other bacteria can further break down and the body can then eliminate.

The enzymes that break down cholesterol

By applying machine learning, the team identified specific enzymes that might be responsible for changing cholesterol into these substances.

In addition, the researchers identified another type of gut bacteria, Eubacterium coprostanoligenes, which also plays a role in lowering cholesterol.

This bacterium contains a gene known to be involved in processing cholesterol. In their latest findings, the team observed that Eubacterium may work together with Oscillibacter to further reduce cholesterol levels.

This indicates that future research focusing on how different types of bacteria interact could provide deeper insights into the complex ways the gut microbiota influences human health.

The researchers are aiming to understand how the complex world inside our guts works by starting with one tiny organism or gene at a time.

They believe this careful approach will help them figure out the system’s workings and create targeted treatments that could directly target harmful microbes.

How our gut flora affects heart disease risk

Two experts, who were not involved in this research, spoke to Medical News Today about the study.

Cheng-Han Chen, MD, board certified interventional cardiologist and medical director of the Structural Heart Program at Memorial Care Saddleback Medical Center in Laguna Hills, CA, said, “the gut microbiome is increasingly being understood as playing a major role in human health, including cardiovascular health.”

“This study utilized metagenomic and metabolomic techniques to identify and focus on a specific species of gut bacteria (Oscillibacter) that appeared to be associated with lower stool and blood cholesterol levels, likely due to their cholesterol-metabolizing properties. As more research is performed to understand the connections between the microbiome and cardiovascular disease, we will be able to identify many more bacterial species that play a role in regulating our cardiovascular risk factors.”
— Dr. Cheng-Han Chen

Chen pointed out that “as gut uptake and metabolism of fats and cholesterol affects our blood cholesterol levels, it is important for us to understand the mechanisms by which this occurs.”

“This research can potentially lead to therapeutics that help our natural gut flora better maintain a favorable blood cholesterol profile, which in turn may even lead to improved cardiovascular health,” he explained.

Using probiotics to target cholesterol

Yu-Ming Ni, MD, board certified cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, agreed, saying, “there’s been a lot of interest in the effect of the microbiome on general health.”

“We coexist with trillions of organisms on our skin and in our intestinal and genitourinary tract. These organisms play a critical role in our ability to fight off external pathogens, in the metabolism of food, and in the health of our immune system. Specifically, this study shows that there are bacterial strains that may affect cholesterol exposure in the intestinal tract.”
— Dr. Yu-Ming Ni

“The discovery of the cholesterol metabolizing properties of Oscillibacter bacteria is fascinating, and it suggests the possibility of the use of this probiotic strain as a therapeutic agent for treating high cholesterol,” Ni said.

However, Ni also noted a few limitations of the study.

“Given that this study was in vitro, it is too early to tell whether the cholesterol effects of this organism in the human body can be replicated. More importantly, we don’t know what other effects this organism may have on the human body, and these other effects may be harmful,” he said.

Ni noted that “further study is needed in actual patients to determine if this organism can play a helpful role in reducing cholesterol uptake.”

Serotonin-Producing Gut Bacteria in Newborns Shields Against Allergies

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Summary: New research highlights the critical role of unique gut bacteria in newborns, producing serotonin to educate immune cells and prevent allergic reactions early in life.

The study reveals that these bacteria encourage the development of T-regulatory cells, crucial for suppressing inappropriate immune responses and preventing autoimmune diseases. This work suggests that before the neonatal gut matures to produce its own neurotransmitters, specific bacteria supply essential serotonin, promoting a balanced immune system.

Such findings underscore the importance of early exposure to beneficial bacteria for preventing allergies and potentially autoimmune diseases later in life.

Key Facts:

  1. Serotonin-Producing Gut Bacteria: Newly born infants’ guts harbor special bacteria that produce serotonin, crucial for developing a healthy immune system by fostering T-regulatory cells.
  2. Prevention of Allergies: This mechanism helps in preventing dangerous allergic reactions to food and beneficial microbes by maintaining a high level of serotonin, which keeps the immune response in check.
  3. Critical Early Development Role: The research emphasizes the significance of the right microbial exposure after birth, suggesting a potential link between reduced diversity in gut bacteria due to modern lifestyles and the rise in food allergies among children in developed countries.

Source: Weill Cornell University

Weill Cornell Medicine investigators discovered that unique bacteria colonize the gut shortly after birth and make the neurotransmitter serotonin to educate gut immune cells. This prevents allergic reactions to food and the bacteria themselves during early development.

The preclinical study, published in Science Immunology on Mar. 15, showed that bacteria abundant in the guts of newborns produce serotonin, which promotes the development of immune cells called T-regulatory cells or Tregs.

These cells suppress inappropriate immune responses to help prevent autoimmune diseases and dangerous allergic reactions to harmless food items or beneficial gut microbes.

This shows a baby in a field of flowers.
The researchers observed that the neonatal mouse gut had much higher levels of neurotransmitters, including serotonin, than the adult gut.

“The gut is now known as the second human brain as it makes over 90 percent of the neurotransmitters in the human body. While neurotransmitters such as serotonin are best known for their roles in brain health, receptors for neurotransmitters are located throughout the human body,” explained the study’s senior author, Dr. Melody Zeng, an assistant professor of immunology in the Gale and Ira Drukier Institute for Children’s Research and the Department of Pediatrics at Weill Cornell Medicine.

Gut Bacteria in Babies Provide a Helping Hand

The researchers observed that the neonatal mouse gut had much higher levels of neurotransmitters, including serotonin, than the adult gut.

“So far, almost all studies of gut neurotransmitters were conducted in adult animals or human subjects, where a specific gut cell type called enterochromaffin cells produce neurotransmitters,” said Dr. Zeng.

“However, we discovered that this isn’t the case in the newborn gut where most of the serotonin is made by bacteria that are more abundant in the neonatal gut.”

This was also confirmed in babies through a human infant stool biobank that the Zeng lab has established in collaboration with the Neonatal Intensive Care Unit in the NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns. These samples were obtained with parental consent and deidentified.

The study results suggest that before the neonatal gut is mature enough to make its own neurotransmitters, unique gut bacteria may supply neurotransmitters that are needed for critical biological functions during early development.

“We found that gut bacteria in young mice not only directly produce serotonin but also decrease an enzyme called monoamine oxidase that normally breaks down serotonin, thus keeping gut serotonin levels high,” said the study’s lead author Dr. Katherine Sanidad, postdoctoral associate in pediatrics at Weill Cornell Medicine.

The high serotonin levels shift the balance of immune cells by increasing the number of Tregs, which helps prevent the immune system from overreacting and attacking gut bacteria or food antigens. “The neonatal gut needs these serotonin-producing bacteria to keep the immune system in check,” Dr. Sanidad added.

Healthy Immune System Helps Later in Life

Dr. Zeng noted that this work underscores the importance of having the right types of beneficial bacteria soon after birth. Babies in developed countries have better access to antibiotics, less exposure to diverse microbes in their clean environments and potentially unhealthy diets that may significantly impact the abundance of serotonin-producing bacteria in their intestines.

As a result, these babies may have fewer Tregs and develop immune reactions to their own gut bacteria, or allergies to food. This may be one reason food allergies have become increasingly common in children, particularly in developed countries.

“If educated properly, the immune system in babies would recognize that things like peanuts and eggs are okay, and it doesn’t have to attack them,” she said. This may also have an impact on developing autoimmune diseases—when the immune system attacks the body’s own healthy cells—later in life.

The team next plans to look at bacteria in human infant stool samples to measure their production of serotonin, other neurotransmitters and molecules that may help train the immune system to prevent future immune-related diseases, such as allergies, infections and cancer.

“It’s essential to understand how the immune system is trained during early life, but this is understudied in newborns and children. Further studies of these developmental periods may hopefully lead us to mitigation approaches to reduce the risk of inflammatory diseases like food allergies and inflammatory bowel disease later in life,” Dr. Sanidad said.

Funding: Dr. Melody Zeng’s lab is supported in part by the National Institutes of Health grants R01HD110118, R01HL169989, R21CA270998, and K01DK114376; The Starr Cancer Consortium; the Hartwell Foundation; and the Jill Roberts Center for Inflammatory Bowel Disease, the Children’s Health Council, and the Drukier Institute for Children’s Health at Weill Cornell Medicine.

Abstract

Gut bacteria-derived serotonin promotes immune tolerance in early life

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined.

Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown.

We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine.

Oral gavage of serotonin into neonatal mice resulted in long-term T cell–mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria.

Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

Helpful Gut Bacteria Seem to Reduce Allergic Disease in Kids

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In babies, the right combo of gut bacteria might stave off later allergies, so scientists are testing “cocktails” of helpful microbes as therapy

Illustration of a sick person blowing into a tissue.

I stopped sending peanut butter and jelly sandwiches to school with my kids around 2007. That was roughly the moment when people started talking about a dramatic rise in the number of children with serious nut allergies. Cases of all kinds of allergies in youngsters have increased since then. The prevalence of asthma has doubled since the 1980s, and more than one quarter of children have eczema, food allergies, or hay fever or other seasonal allergies.

A host of studies from around the world strongly suggest that our allergy epidemic is the result of reduced exposure to germs in early life. During this critical window of time, an infant’s immune system learns to defend against dangerous microbes and to tolerate good ones that can live in the gut and aid in processes such as digestion. This immune education comes from encountering a wide variety of germs. But as social habits have changed, leading us to spend more time indoors, these encounters have been reduced, and immune overreactions—allergies—have climbed.

This idea, introduced decades ago as the “hygiene hypothesis” and refined over the years, is supported by epidemiological studies showing that having older siblings, attending day care, living on a farm and having pets protect against allergies. But more antiseptic early lives—delivery by cesarean section, not receiving breast milk and getting antibiotic therapy in the first year of life—seem to increase risk.

Now stronger evidence is emerging that clarifies the ways that microbes inside children’s guts can trigger allergies. Scientists are working out how the presence or absence of certain bacteria in kids’ digestive systems affects allergic risk, thanks to technological advances that let researchers identify more types of gut microbes. Someday it might be possible to replace certain microbes in children and in the population at large and thereby lessen people’s susceptibility to allergies.

In infancy the gut microbiomes of children who later develop allergies or asthma look different from those of children who don’t go on to have allergies. “Children who are at the highest risk are missing important health-promoting bacteria in that first year of life,” says Stuart Turvey, a pediatric immunologist at the University of British Columbia and British Columbia Children’s Hospital.

Among other things, the presence of certain innocuous bacteria early on creates a welcoming environment that allows other, helpful bacteria to follow in predictable waves. If those first “keystone” bacteria are missing, the subsequent waves of colonization are delayed or disrupted. “Microbial exposures in early life can really shape the immune system in ways that they can’t much later in life,” says Supinda Bunyavanich, a pediatric allergist and immunologist at Mount Sinai in New York City.

In a study of more than 1,100 children published in 2023, Turvey and his colleagues found that children who had these microbiome disruptions at age one were more likely to be diagnosed with eczema, food allergies, allergic rhinitis or asthma at age five. “Not every kid gets all four [diagnoses], but often the kids who had two or more had a more pronounced microbiome imbalance signature,” he says.

Work in mice has helped researchers determine which microbes are especially influential and why. Talal Chatila, a physician who works in the food allergy program at Boston Children’s Hospital, found that giving allergy-prone mice microbes from the orders Clostridiales and Bacteroidales protected the animals from developing food allergies. “Particular microbes within a healthy gut act to suppress allergic responses,” Chatila says. One way they do that is by promoting the formation of regulatory T cells, which help to control immune system responses.

Another type of bacteria that has a positive effect on humans is Bifidobacterium infantis, which eats sugars in breast milk and is more abundant in some children who are breastfed. B. infantis was once common in people’s guts but is much less so now in Western countries. “Only 16 percent of Canadian kids have this, and rates are lower in the U.S.,” Turvey says. Among youngsters who had to have antibiotics in infancy, the presence of B. infantis protected them against developing asthma by age five, Turvey’s studies have shown. Antibiotics reduce microbial diversity in the gut, but these particular bacteria seem to counter those negative effects.

Multiple clinical trials are underway to test allergy treatments with “cocktails” of selected bacteria. Most of these trials involve treating infants who are at high risk for allergies and then following them through childhood to see whether the treatments keep the children allergy-free. For prebiotics and probiotics now on the market, there is no convincing evidence that they can make allergies go away.

Biotherapeutics are not the only answer. Avoiding unnecessary cesarean sections and antibiotics and enacting policies that support breastfeeding could also help, Bunyavanich says. She is working on a trial comparing children born vaginally, who are exposed to microbes in the birth canal, with children born by C-section who had the mother’s vaginal fluids applied at birth. Both will be compared with children born by C-section without any microbial exposure.

The scientists will follow the kids through early childhood to see who has increased risk of allergies. If this and the other trials do reduce allergies, bringing back the microbes we’ve lost could turn out to be a key health strategy.

Gut bacteria linked to colorectal cancer in young people

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Certain gut bacteria reside in colorectal tumors, but the species differ depending on a patient’s age, offering hope that our gut tenants could serve as early warning signs of cancer in young people.

Studies of microbes in tumors could potentially help scientists develop new ways of screening for colorectal cancer, some scientists think. (Image credit: PonyWang via Getty Images)

Colorectal cancer most often affects people over age 50, but it’s on the rise in younger people, who are rarely offered screening to catch these cancers early. Now, a new study hints that microbes found in the tumors of younger and older cancer patients differ, and this could potentially offer new means for early diagnosis.

In new research, published Feb. 1 in the journal eBioMedicine, scientists probed the gut microbiome — the community of microbes that populate the lower digestive tract — in cancer patients of two age groups. They included 136 people under age 50 with a median age of 43 and 140 people over 50 with a median age of 73. The researchers found that distinct sets of bacteria were present in tumors of older and younger people with colorectal cancer.

Colorectal cancer is often, but not always, hereditary

“We know that many of these early-onset cancers are not directly linked to a genetic factor,” said Laura Valle, a cancer researcher at the Catalan Institute of Oncology, IDIBELL in Spain who was not involved in the new study. Environmental factors, such as alcohol consumption and high-fat, low-fiber diets, are also associated with this cancer, whereas people who eat fiber-rich foods appear less likely to develop it. The foods and drinks people consume are known to affect their gut bacteria, suggesting a link between these factors.

“We have always hypothesized that early-onset colorectal cancers will have something to do with the microbiome,” Valle told Live Science.

To find out which gut bacteria thrive inside the tumors of older and younger people, researchers retrospectively looked at samples of tissue taken from cancer patients, sampling the microbiome directly from tumors and from nearby noncancerous tissue.

In both age groups, tumors harbored a smaller variety of bacterial species than surrounding tissue, and this loss of diversity was more dramatic in the older group. This suggests that only a portion of gut bacteria can survive in a tumor, a low-oxygen environment that’s often inflamed by the immune system.

However, it’s not yet clear what the bacteria do inside the tumors or why certain species thrive there. “This is what exactly needs to be figured out using mechanistic studies,” said lead study author Naseer Sangwan, a microbiologist at the Cleveland Clinic Lerner Research Institute.

Beyond looking at overall changes in microbial diversity, Sangwan and colleagues found certain species that were more often found in tumors of one age group over the other. They also found that different types of colorectal tumors — such as colon carcinomas and rectal tumors — housed distinct bacterial species.

Neither Sangwan nor Valle wanted to speculate about how any given species might affect the growth or spread of a tumor.

“It’s usually not just one bacterium,” Valle said; the community of bacteria in a given tumor should be considered as a whole, not as individual parts. In other words, the microbes interact in complex ways and could collectively influence a tumor’s behavior.

At this point, the study has revealed a correlation between certain gut microbes and colorectal cancer. Although this doesn’t prove that these bacteria cause colorectal cancer, there’s a possibility of a causal link. One hypothesis is that the presence of certain bacterial species or a combination of species could either prevent or promote the cancer.

For example, a broad group of bacteria called Akkermansia, which were more often found in the younger group, were predominantly present in small tumors. This led the scientists to speculate whether these microbes might somehow limit tumor growth. In fact, a mouse study revealed that probiotic treatment — which involved consuming live cultures of Akkermansia — could hinder tumor growth.

Such findings lead some scientists to wonder whether probiotics could control or limit colorectal cancers in human patients. Valle said she’s skeptical, citing evidence that treatments designed to alter the gut microbiome don’t necessarily have lasting effects.

Sangwan, on the other hand, is excited about the prospects for harnessing the microbiome for early cancer diagnosis. The eventual goal is to “accurately predict the occurrence of cancer in young people,” he said.

Early diagnosis of colorectal cancer isn’t usually an option in people under age 45, who have yet to undergo their first colonoscopy. “If you get symptoms from a cancer in the colon, it usually means that it’s quite advanced,” Valle noted. However, lowering the screening age might not be the best solution.

“It’s invasive, and there is a percentage of adverse effects,” such as punctures in the colon, she said. But if we know what bacteria can be found in tumors, it might be possible to detect the microbes in stool samples from young people, she suggested, thus narrowing down who should be screened for signs of cancer.

The study had a small number of participants, so it requires validation in a larger group, Valle said. In addition, many ethnic groups were missing from the study — such as Black, Asian, Hispanic, Native American and Pacific Islander backgrounds — so scientists aren’t certain these results would be similar in patients in these groups.

“We will follow up on this using bigger cohorts of diverse people and ethnicities,” Sangwan said.

New gut-brain circuits found for sugar and fat cravings

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Gut Bacteria Can Protect Stem Cell Transplant Patients from Harmful Immune Reactions

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After stem cell transplantation, donated immune cells sometimes lead to graft versus host disease (GvHD). Now researchers at the Technical University of Munich (TUM) and the Universitätsklinikum Regensburg (UKR) report that GvHD is much less common when certain microbes are present in the gut. In the future, it may be possible to deliberately bring about this protective composition of the microbiome.

Their study “Bacteria and Bacteriophage Consortia are Associated with Protective Intestinal Metabolites in Patients Receiving Stem Cell Transplantation” appears in Nature Cancer.

It has been known for some time that microbes in the gut play a role in determining whether GvHD occurs. A team working with Erik Thiele Orberg, PhD, who heads a research group at the clinic and polyclinic for internal medicine III at TUM, Ernst Holler, PhD, senior professor of allogenic stem cell transplantation at UKR, and Hendrik Poeck, PhD, at UKR’s clinic and polyclinic for internal medicine, describes in Nature Cancer how the gut microbiome must be composed to provide protection.

Gut Bacteria Can Protect Stem Cell Transplant Patients from Harmful Immune Reactions“The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of  intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics, and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages. correlating with the production of immunomodulatory metabolites (IMMs),” write the investigators.

“Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA): acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.”

Seventy-eight patients observed

The researchers studied stool samples from 78 patients at the two university clinics and tracked them over two years following stem cell transplantation. They used the results to develop a risk index indicating the probability of a rejection reaction. “Instead of counting bacteria, we measured the quantities of certain metabolites produced by the microbes,” says Thiele Orberg.

These immuno-modulatory microbial metabolites (IMMs) influence the immune system and the body’s regenerative capacity. “It is remarkable that a positive prognosis does not depend only on IMMs from bacteria,” says Elisabeth Meedt, MD, a physician at UKR and co-first author of the article. “We demonstrated that certain viruses in the gut–the bacteriophages–also play a role. This alone offers an impressive insight into the complex world of our gut microbiome.”

“Patients with a low IMM risk index had a higher chance of survival, showed fewer graft vs. host reactions, and experienced fewer relapses,” adds Poeck, noting that the metabolites are formed mainly by bacteria from the families Lachnospiraceae and Oscillospiraceae combination with the bacteriophages. The researchers at TUM and UKR next want to predict and actively improve patients’ chances at a cure.

“By precisely controlling the composition of fecal microbiota transplants, the gut could be colonized with specific consortia of bacteria and bacteriophages,” explains Hendrik Poeck. “In the coming years, we want to find out whether we can use this approach to prevent graft vs. host reactions as well as relapses.”

Initial experiments with mice reportedly have been successful. As a result, the procedure could now be tested in clinical trials with human patients, according to the scientists.