Vaccine against deadly chytrid fungus primes frog microbiome for future exposure

A new study led by researchers at Penn State found that a new vaccine against the deadly chytrid fungus in frogs can shift the composition of the microbiome, making frogs more resilient to future exposure to the fungus.
Photo Credit: Paul Bonnar

A human's or animal’s microbiome — the collection of often beneficial microorganisms, including bacteria and fungi, that live on or within a host organism — can play an important role in the host’s overall immune response, but it is unclear how vaccines against harmful pathogens impact the microbiome. A new study led by researchers at Penn State found that a new vaccine against the deadly chytrid fungus in frogs can shift the composition of the microbiome, making frogs more resilient to future exposure to the fungus. The study, published June 12 in a special issue of the journal Philosophical Transactions of the Royal Society B, suggests that the microbiome response could be an important, overlooked part of vaccine efficacy.

“The microorganisms that make up an animal’s microbiome can often help defend against pathogens, for example by producing beneficial metabolites or by competing against the pathogens for space or nutrients,” said Gui Becker, associate professor of biology at Penn State and leader of the research team. “But what happens to your microbiome when you get a vaccine, like a COVID vaccine, flu shot, or a live-attenuated vaccine like the yellow fever vaccine? In this study, we used frogs as a model system to start exploring this question.”

Frogs and other amphibians are threatened by the chytrid fungus, which has led to extinctions of some species and severe population declines in hundreds of others across several continents. In susceptible species, the fungus causes a sometimes-lethal skin disease.

Researchers construct the most complex, complete synthetic microbiome

A bacterial cell culture from the Fischbach lab.
Image credit: L.A. Cicero

The microbial community of over 100 bacterial species could help scientists learn more about the connections between the microbiome and human health.

Key studies in the last decade have shown that the gut microbiome, the collection of hundreds of bacterial species that live in the human digestive system, influences neural development, response to cancer immunotherapies, and other aspects of health. But these communities are complex and without systematic ways to study the constituents, the exact cells and molecules linked with certain diseases remain a mystery.

Stanford University researchers have built the most complex and well-defined synthetic microbiome, creating a community of over 100 bacterial species that were successfully transplanted into mice. The ability to add, remove, and edit individual species will allow scientists to better understand the links between the microbiome and health, and eventually develop first-in-class microbiome therapies.

Many key microbiome studies have been done using fecal transplants, which introduce the entire, natural microbiome from one organism to another. While scientists routinely silence a gene or remove a protein from a specific cell or even an entire mouse, there is no such set of tools to remove or modify one species among the hundreds in a given fecal sample.

Infants in industrialized nations are losing a species of gut bacteria that digests breast milk

Credit: Cleyder Duque

Babies in industrialized nations have fewer bacteria that efficiently digest breast milk than babies of a hunter-gatherer group.

The guts of infants are nearly sterile at birth, but they become a community of trillions of microbial cells, known as the microbiome, by the time they reach adulthood. For infants who are breastfed, their health is off to a solid start with milk that provides nutrients for good bacteria that fight off pathogens.

But, according to a study led by researchers at Stanford Medicine, the bacteria efficient at digesting breast milk are being lost as nations industrialize. Because no other bacteria are as adept at digesting milk, researchers are concerned this bacterial exodus could mean rising cases of conditions common in the industrialized world, such as chronic inflammation.

The study found that bacteria in the genus Bifidobacterium — good bacteria that live in the intestines — are the most prevalent species in the microbiome of infants less than 6 months old around the world — regardless of whether they are fed breast milk or formula. Researchers discovered that a species called Bifidobacterium infantis (or B. infantis) — known to efficiently break down a special class of breast milk sugars known as oligosaccharides, as well as boost the immune system and bacterial microbiome development — dominates the gut microbiome of infants in nonindustrialized societies.

In contrast, Bifidobacterium breve, a species with limited capacity to break down milk sugars, is the most prevalent species in infants of industrialized nations.

What Is: The Human Microbiome

The Human Microbiome
Image Credit: Scientific Frontline stock image

The Invisible Organ

The human body is not a sterile, solitary entity. It is a dense, complex, and dynamic ecosystem. Each individual serves as a host to a vast community of microorganisms, collectively known as the human microbiota. This community, which resides in and on the body, is estimated to comprise between 10 trillion and 100 trillion symbiotic microbial cells. Early estimates, which have become a cornerstone of the field, suggested these microbial cells outnumber human cells by a ratio of ten to one. While more recent analyses propose a ratio closer to 1:1, the sheer scale of this microbial colonization remains staggering. These microbial cells, though only one-tenth to one-hundredth the size of a human cell, may account for up to five pounds of an adult's body weight.

This vast microbial community is not a passive passenger. It functions as a "virtual organ" of the body, or more precisely, a "metabolic organ". It is so deeply integrated into our physiology that we are dependent on it for essential life functions, including digestion, immune system development, and the production of critical nutrients.

Maternal microbiome promotes healthy development of the baby

Bifidobacterium breve 
Credit: Hall Lab, Quadram Institute

A new study has found that a species of gut bacteria, known to have beneficial effects for health in mice and humans, changes the mother’s body during pregnancy and affects the structure of the placenta and nutrient transport - which impacts the growing baby.

The bacteria, Bifidobacterium breve, is widely used as a probiotic so this study could point to ways of combating pregnancy complications and ensuring a healthy start in life across the population.

The research involved scientists from the University of Cambridge, the Quadram Institute, and the University of East Anglia and is published today in the journal Cellular and Molecular Life Sciences.

Microbes in our gut, collectively called the gut microbiome, are known to play a key role in maintaining health by combating infections, and influencing our immune system and metabolism. They achieve these beneficial effects by breaking down food in our diet and releasing active metabolites that influence cells and body processes.

Little is known about how these interactions influence fetal development and the baby’s health pre-birth. To address this, Professor Lindsay Hall from the Quadram Institute and University of East Anglia, and Dr Amanda Sferruzzi-Perri and Dr Jorge Lopez-Tello from the University of Cambridge analysed how supplementation with Bifidobacterium bacteria affected pregnancy in mice.

Aging, Frailty, and our Microbiomes

Photo Credit: Magda Ehlers

We humans tend to think we live independently, capable of ensuring our own health and wellbeing. As researchers are increasingly aware, however, our microbiomes—the trillions of microbes that live on and within us—play central roles in our health and susceptibility to different diseases. And as we age, our microbiomes change too, with important health implications over time.

Jackson Laboratory (JAX) Associate Professor Julia Oh, Ph.D., studies the microbiome, particularly the microbes that colonize the skin. While prior research has explored the gut microbiome in the context of aging, to date there has been little insight into the changes that occur in other microbial communities of our body, like the mouth and skin. To further investigate, Oh and her team collaborated with UConn Center on Aging Professors Julie Robison, Ph.D., and George Kuchel, M.D., to study the microbiome of the skin, oral, and gut of older adults compared to younger adults.

Because of the unique design of their study, where they sampled frail older adults inhabiting skilled nursing facilities as well as community-dwelling older adults, they found that the greatest microbiome differences between the groups were associated with increased frailty, not chronological age. A second surprising finding was that microbiome differences between cohorts were most pronounced in the skin, rather than the gut or mouth. Moreover, the skin harbored the greatest number of potential risk factors for infectious disease. The researchers presented their findings in “Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults,” published in Nature Aging.

“This was an extraordinary multidisciplinary effort between our clinical and research team at UConn Center on Aging and The Jackson Laboratory for Genomic Medicine,” says Oh. “We believe this exciting study is an important step to understanding how the microbiome contributes to aging and chronic diseases, in turn allowing us to identify potential interventional targets to improve health across lifespan.”

Some Gut Bacteria Linked to Precancerous Colon Polyps

Scientific Frontline stock graphic

A new study by Harvard Medical School investigators at Massachusetts General Hospital has linked certain types of gut bacteria to the development of precancerous colon polyps. Their results are published in Cell Host & Microbe.

“Researchers have done a lot of work to understand the relationship between the gut microbiome and cancer. But this new study is about understanding the microbiome’s influence on precancerous polyps,” said co-corresponding author Daniel C. Chung, HMS professor of medicine, medical co-director of the Center for Cancer Risk Assessment at Mass General Cancer Center, and a faculty member of the gastroenterology division at Mass General.

“Through the microbiome, we potentially have an opportunity to intervene and prevent colorectal cancer from forming,” he said.

Colorectal cancer is the second-leading cause of cancer-related deaths in the U.S., and rates of colorectal cancer are rising among young adults.

Nearly all colorectal cancers arise from a precancerous polyp. One of the best ways to reduce the incidence of colorectal cancer is to stop the growth at the polyp stage.

A mother mouse needs a diverse gut microbiome to form a healthy placenta

“More and more evidence is suggesting that [the gut microbiome] begins to exert its influence even during prenatal life,” said UCLA’s Elaine Hsiao.
Photo Credit: Karsten Paulick

The bacteria found naturally in the digestive tract does a lot more than help digest food.

Scientists have established that these microbial communities are also involved with the immune system and play a role in mental health. Now, they can add helping grow a healthy placenta during pregnancy to the list of unexpected ways the gut microbiome influences health and well-being.

New research led by UCLA scientists and published today in the journal Science Advances shows that mice with depleted gut microbiomes had smaller placentas than normal mice and that the network of blood vessels between the placenta and the fetus was also less developed.

Either of these conditions could deprive a fetus of nutrients, oxygen and other things it needs to grow. But when malnourished pregnant mice that had been fed low-protein diets and had diminished microbiomes were supplemented with short-chain fatty acids, which are produced by gut microbes, their placentas grew to normal size, the researchers said.

The new findings add to mounting evidence that in addition to its many other activities, the gut microbiome plays a role in the formation of new blood vessels, a process known as angiogenesis. They also show that byproducts of microbe metabolism known as metabolites play key roles in feto-placental development.

Mice study suggests metabolic diseases may be driven by gut microbiome, loss of ovarian hormones

Mice that received fecal implants from donors that had their ovaries removed gained more fat mass and had greater expression of liver genes associated with inflammation, Type 2 diabetes, fatty liver disease and atherosclerosis. The findings may shed light on the greater incidence of metabolic dysfunction in postmenopausal women. The team members included, from left: molecular and integrative physiology professor Erik R. Nelson; Kelly Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition; and animal sciences professor Brett R. Loman.
  Photo Credit: Fred Zwicky

The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers found in a new rodent study.

The findings, published in the journal Gut Microbes, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.

“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper.  “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”

A New Method for Assessing the Microbiome of the Human Gut

A technique called 'bead beating.'
Photo Credit: Courtesy of California Institute of Technology

The gut microbiome—the population and variety of bacteria within the intestine—is thought to influence a number of behavioral and disease traits in humans. Most obviously, it affects intestinal health. Cancer, inflammatory bowel disease, and celiac disease, for example, are all affected by the gut microbiome. But recent research at Caltech and other research centers has identified connections between the gut microbiome and diseases such as Parkinson's disease and multiple sclerosis as well as links between the gut microbiome and the presence of autistic behaviors, anxious behaviors, and a propensity to binge-eat sweets. (Most of this work has been done in the laboratory of Sarkis Mazmanian, Caltech's Luis B. and Nelly Soux Professor of Microbiology, who works mainly on mouse models.)

Looking directly at the human gut and the bacteria that make this space their home is often performed with sequencing—a process that analyzes the DNA sequences that make up each organism. However, this process is difficult in the intestine largely because the amount of microbial DNA in the gut is miniscule in comparison to the amount of host DNA. In intestinal tissue, roughly 99.99 percent of the DNA present is from the host organism; only 0.01 percent is microbial DNA.

However powerful the effects of these microbes, it is hard to understand their role without knowing their composition. Microbiome studies often rely on studies of feces and saliva, but these are quite different from the ecosystem of the gut itself.

How Studying Poop May Help Us Boost White Rhino Populations

White Rhinoceros with baby, being protected from poachers. Shot in the Kruger National Park, South Africa.
Photo Credit: Nadine Venter

Researchers at North Carolina State University have identified significant differences in the gut microbiome of female southern white rhinos who are reproducing successfully in captivity, as compared to females who have not reproduced successfully in captivity. The work raises questions about the role that a particular genus of gut microbes may be playing in limiting captive breeding of this rhinoceros species.

“Our work focuses on the southern white rhinoceros (Ceratotherium simum simum), because while it is not yet endangered, species numbers are declining in the wild due to poaching,” says Christina Burnham, first author of a paper on the work and a former graduate student at NC State.

“There is a significant population of southern white rhinos under human care in the United States, but there have been challenges in getting many of these animals to reproduce successfully. It is critical we understand why, as the managed rhinos serve as important assurance populations in case wild rhino numbers continue to fall. We wanted to know how the gut microbiome may influence the reproductive ability of these rhinos.”

Mothers Influence Gut Microbial Development in Wild Primates

A baby gelada foraging in Simien Mountains National Park in Ethiopia. Their early-life gut microbiome, from infancy through first years of life, are shown to be influenced by bacteria likely passed down from mom.
Credit: Sharmi Sen

The bacteria that reside in the human gut (“the gut microbiome”) are known to play beneficial and harmful roles in human health. Because these bacteria are transmitted through milk, mothers can directly impact the composition of bacteria that their offspring harbor, potentially giving moms another pathway to influence their infant’s future development and health. A study of wild geladas (a non-human primate that lives in Ethiopia) provides the first evidence of clear and significant maternal effects on the gut microbiome both before and after weaning in a wild mammal. This finding, published in Current Biology, suggests the impact of mothers on the offspring gut microbiome community extends far beyond when the infant has stopped nursing.

A research team co-led by Stony Brook University anthropologist Amy Lu, and biologists Alice Baniel and Noah Snyder-Mackler at Arizona State University, came to this conclusion by analyzing one of the largest datasets on gut microbiome development in a wild mammal.

“Early life gut microbial development is known to have a large impact on later life health in humans and other model organisms,” said Lu, associate professor in the Department of Anthropology in the College of Arts and Sciences at Stony Brook University. “Now we have solid evidence that mothers can influence this process, both before and after weaning. Although we’re not 100% certain how mothers do this, one possible explanation is that they transfer specific bacteria to their offspring.”

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

 

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

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

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

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

Scientists link certain gut bacteria to lower heart disease risk

Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green).
Image Credit: Ahmed Mohamed 

Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the Broad Institute of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in Cell, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.

Members of Ramnik Xavier’s lab, Broad’s Metabolomics Platform, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called Oscillibacter take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.

“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 Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the Broad. He is also a professor at Harvard Medical School and Massachusetts General Hospital.

How the gut creates a cozy home for beneficial microbiome species

Image Credit: Courtesy of Carnegie Institution for Science

The digestive tract of fruit flies remodels itself to accommodate beneficial microbiome species and maintain long-term stability of the gut environment, according to new research led by Carnegie’s William Ludington and Allan Spradling. Their findings are published in Nature Communications.

The gut microbiome is an ecosystem of hundreds to thousands of microbial species living within the human body. These populations affect our health, fertility, and longevity. But there is still so much to learn about how these microbial species interact with our bodies and with each other.

“Every day, we encounter, and even ingest, a diverse array of bacterial species,” explained Ludington, who has been probing microbiome acquisition and composition for several years at Carnegie. “Despite this, the gut microbiome remains relatively stable over time—a phenomenon that is maintained across many species ranging from mammals to insects.”

He, Spradling, and their collaborators wanted to determine how our guts can maintain such remarkably consistent microbiome compositions. Because the human microbiome is so complex, they studied fruit flies, which are only colonized by a handful of microbial species.

Personalized Gut Microbiome Analysis for Colorectal Cancer Classification with Explainable AI

Explainable AI offers a promising solution for finding links between diseases and certain species of gut bacteria, finds a research team at Tokyo Tech. Using a concept borrowed from game theory, the researchers developed a framework that reveals which bacterial species are closely associated with colorectal cancer in individual subjects, providing a more reliable way to find and characterize disease subgroups and identify biomarkers in the gut microbiome.

The gut microbiome comprises a complex population of different bacterial species that are essential to human health. In recent years, scientists across several fields have found that changes in the gut microbiome can be linked to a wide variety of diseases, notably colorectal cancer (CRC). Multiple studies have revealed that a higher abundance of certain bacteria, such as Fusobacterium nucleatum and Parvimonas micra, is typically associated with CRC progression.

Tracing tomatoes’ health benefits to gut microbes

The tomatoes used in the study were developed at Ohio State and are the type typically found in canned tomato products.
Photo Credit: Couleur

Two weeks of eating a diet heavy in tomatoes increased the diversity of gut microbes and altered gut bacteria toward a more favorable profile in young pigs, researchers found.

After observing these results with a short-term intervention, the research team plans to progress to similar studies in people, looking for health-related links between tomatoes in the diet and changes to the human gut microbiome – the community of microorganisms living in the gastrointestinal tract.

“It’s possible that tomatoes impart benefits through their modulation of the gut microbiome,” said senior author Jessica Cooperstone, assistant professor of horticulture and crop science and food science and technology at The Ohio State University.

“Overall dietary patterns have been associated with differences in microbiome composition, but food-specific effects haven’t been studied very much,” Cooperstone said. “Ultimately we’d like to identify in humans what the role is of these particular microorganisms and how they might be contributing to potential health outcomes.”

African Wildlife Poop Sheds Light on What Shapes the Gut Ecosystem

Photo Credit: James C. Beasley

A study of elephants, giraffes and other wildlife in Namibia’s Etosha National Park underscores the ways in which the environment, biological sex, and anatomical distinctions can drive variation in the gut microbiomes across plant-eating species. Because the gut microbiome plays a critical role in animal health, the work can be used to inform conservation efforts.

“This study is valuable because Etosha gave us the opportunity to sample such a large number of species under different environmental conditions,” says Erin McKenney, co-author of a paper on the work and an assistant professor of applied ecology at North Carolina State University. “That gives us meaningful insight into the role the environment plays in shaping the gut microbiome of herbivores.

“Unfortunately, this study may also be important for a second reason,” McKenney says. “Etosha is experiencing devastating wildfires affecting a huge section of the park. Because our samples were taken before the wildfires, these findings could inform recovery efforts by helping us understand how species’ microbiomes are adjusting to changes in diet that stem from the fire’s impact on the landscape.”

Revealed: Some microbiome species regulate their entire bacterial ecosystem

Image Credit: Scientific Frontline 

A team of mathematicians and biologists led by Carnegie’s Will Ludington and Technische Universität Berlin’s Michael Joswig developed a new approach to reveal key genes and species that regulate biological networks. Their work, published this week in Proceedings of the National Academy of Sciences, identifies genes in cells and species in ecosystems that sit at the top of a regulatory hierarchy and drive evolutionary and ecological trajectories.

Charles Darwin concluded On the Origin of Species with the famous “tangled bank” analogy to explain how organisms in an ecosystem affect one another’s fitness. “It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth,” Darwin wrote. “And to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us.” 

To map these interactions in ecosystems, ecologists use network analysis to study the connections. Keystone species, such as wolves, have a disproportionately large impact on their communities and the other organisms within them.

Scientists discover links between Alzheimer’s disease and gut microbiota

Photo (L-R): Dr Stefanie Grabrucker (a postdoctoral researcher) and Professor Yvonne Nolan, of APC Microbiome Ireland and the Department of Anatomy and Neuroscience.
Photo Credit: Ms Bereniece Riedewald.

Researchers have discovered the link between gut microbiota and Alzheimer’s disease.

For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.

The research was led by Professor Yvonne Nolan, APC Microbiome Ireland, a world leading SFI funded research center based at University College Cork (UCC), and the Department of Anatomy and Neuroscience, UCC, with Professor Sandrine Thuret at King’s College London and Dr Annamaria Cattaneo IRCCS Fatebenefratelli, Italy. The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer’s disease due to its particular susceptibility to lifestyle and environmental influences.

Published in Brain, the study shows that memory impairments in people with Alzheimer’s could be transferred to young animals through transplant of gut microbiota. Alzheimer’s patients had a higher abundance of inflammation-promoting bacteria in fecal samples, and these changes were directly associated with their cognitive status.