Your microbiome shapes your life. But where did it come from?

Microbiome Acquisition


Artist’s concept of this research that probes the odds of a new species being acquired by a microbiome ecosystem created by Navid Marvi, courtesy of the Carnegie Institution for Science. CREDIT By Navid Marvi, courtesy of the Carnegie Institution for Science.

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 even our longevity. But how do they get there in the first place?

New collaborative work led by Carnegie’s William Ludington reveals crucial details about how the bacterial communities that comprise each of our individual gut microbiomes are acquired. These findings, published in the Proceedings of the National Academy of Sciences, have major implications for treatments such as fecal transplants and probiotic administration.

“There is a huge amount of variation in microbiome composition between individuals,” Ludington explained. “For example, if you look at the sum total of all of the bacterial species that are adapted to live in the gastrointestinal systems of humans, most of these are not present in a majority of people. That’s how incredibly diverse these gut microbial populations are.”

A combination of elements, including genetics, diet, and environment contribute to the differences between our microbiomes. But there isn’t a direct line between these inputs and the species that successfully colonize our guts. There’s an element of chance at play each time we are exposed to a new microbe as to whether it will be acquired and become a member of our gut ecosystem. Ludington and his collaborators set out to understand the factors that shape the odds of this colonization process.

Although many researchers have studied microbiome compositions in natural populations, there have been few attempts to use a controlled environment to reveal the process by which new species successfully join the gut microbial ecosystem. Ludington and his collaborators—Eric Jones and David Sivak of Simon Fraser University and Jean Carlson of UC Santa Barbara—developed a new ecological model to understand how we acquire the specific mix of microbes that are individual to our own particular gut communities.  

Working in the comparatively much less complicated microbiomes of fruit flies, the team showed that exposure to a microbial species does not guarantee its successful incorporation into the microbiome ecosystem. They found that the state of the microbiome, and interactions between existing microbiome member species, sets the odds for whether a newly encountered bacteria is added into the mix.

“Even among genetically identical flies that lived in the same housing and were fed the same diets, we saw variations in microbiome composition,” Sivak said.

The researchers then used these results to build mathematical models that could probe increasingly complex scenarios by which new microbiome species could be acquired, leading to their breakthrough understanding of the community factors that shape membership in the microbiome ecosystem.

“Think of microbiome composition as a big party where the social dynamics determine who leaves early and who stays until dawn,” said Ludington.

Added Jones, the paper’s first author: “Bacterial colonization depends on a number of complicated factors that we’re just starting to understand.  We showed, for example, that some groups of species facilitate each other’s colonization and are therefore more likely to coexist.”

These group interactions have exciting implications for how microbiomes are transmitted between individuals, including how medical professionals might drive a person’s microbiome towards a desired composition.

“The beauty of the mathematical approach we deployed is that it acknowledges that colonization is a roll of the dice, but we are now able to attribute the weighting of the dice to biological interactions with a molecular basis that has been honed by evolution,” said Carlson.

The team’s findings provide a framework for quantitatively examining the mechanisms that therapies such as fecal transplants and probiotics depend upon, advancing toward the eventual goal of personalized microbiome medicine.        

Scientists identify gut-derived metabolites that play a role in multiple sclerosis

Gut Bacteria and Multiple Sclerosis

Scientists identify gut-derived metabolites that play a role in neurodegeneration

 

A New York-based, multi-institutional research team has found high levels of three toxic metabolites produced by gut bacteria in the cerebrospinal fluid and plasma samples of multiple sclerosis (MS) patients. The important findings, published in the journal Brain, further scientists’ understanding of how gut bacteria can impact the course of neurological diseases by producing compounds that are toxic to nerve cells.

Previously published evidence has supported the concept that an imbalance in the gut microbiota—the community of organisms that live in the human intestines—may underly a range of neurological disorders. Researchers also found that certain gut bacteria are either enriched or depleted in MS patients compared to healthy individuals, but it is unclear how these microbes communicate with the brain and affect the neurodegenerative disease process.

“Our findings suggest that MS patients’ gut bacteria produce and release large amounts p-cresol-sulfate, indoxyl-sulfate and N-phenylacetylglutamine into the bloodstream, and they eventually reach the cerebrospinal fluid,” said Hye-Jin Park, one of the lead authors on the study and a research associate with the Neuroscience Initiative at the Advanced Science Research Center at the Graduate Center, CUNY (CUNY ASRC) “Once there, these toxic metabolites bathe the brain and spinal cord, and potentially play a role in the destruction of the myelin sheath that protect nerves.”

For the study, the research team obtained blood and cerebrospinal fluid samples from volunteer patients at the Multiple Sclerosis Center of Northeastern New York. Samples were taken from patients before and after treatment with the disease modifying therapy dimethyl fumarate (DMF), which has been reported to have a profound effect on reshaping the gut microbiome of MS patients. The analyzed data allowed researchers to identify an abundance of the three toxic metabolites in MS patients not treated with DMF compared to healthy individuals. They also noted a reduction in the metabolites following treatment with DMF.

“The presence of high levels of these toxic metabolites also correlates with biomarkers of neurodegeneration in MS patients, and with the ability to impair neuronal function of cultured cells in the laboratory,” said Achilles Ntranos, a lead author of the study and assistant professor of Neurology at the Icahn School of Medicine at Mount Sinai, where a second set of samples was collected from MS patients.

“This is an exciting and significant discovery,” said Patrizia Casaccia, the study’s primary investigator and the founding director of the CUNY ASRC’s Neuroscience Initiative. “This work not only furthers our understanding of the role of gut-brain communication in neurodegenerative disease progression, but also provides a potential metabolic target for develop new MS Therapies.”

Gut bacteria associated with chronic pain

People with fibromyalgia show variations in microbiome composition

Bacterial Species Composition

Bacterial species which were found in greater quantities in individuals with fibromyalgia (left) versus species which were found in greater quantities in healthy individuals (right).CREDIT Dr. Amir Minerbi

Scientists have found a correlation between a disease involving chronic pain and alterations in the gut microbiome.

Fibromyalgia affects 2-4 percent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by widespread chronic pain. In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia. Approximately 20 different species of bacteria were found in either greater or are lesser quantities in the microbiomes of participants suffering from the disease than in the healthy control group.

Greater presence or absence of certain species of bacteria

Human Gut Microbiome Composition

Human gut microbiome composition shows an enormous richness. Each circle represents a bacterial species, while the different colours mark different bacterial phyla. CREDIT Dr. Amir Minerbi

“We used a range of techniques, including Artificial Intelligence, to confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age, and so on, which are known to affect the microbiome,” says Dr. Amir Minerbi, from the Alan Edwards Pain Management Unit at the McGill University Health Centre (MUHC), and first author on the paper. The team also included researchers from McGill University and Université de Montréal as well as others from the Research Institute of the MUHC.

Dr. Minerbi adds, “We found that fibromyalgia and the symptoms of fibromyalgia – pain, fatigue and cognitive difficulties – contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease. We also saw that the severity of a patient’s symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria – something which has never been reported before.”

Are bacteria simply the markers of the disease?

At this point, it’s not clear whether the changes in gut bacteria seen in patients with fibromyalgia are simply markers of the disease or whether they play a role in causing it. Because the disease involves a cluster of symptoms, and not simply pain, the next step in the research will be to investigate whether there are similar changes in the gut microbiome in other conditions involving chronic pain, such as lower back pain, headaches and neuropathic pain.

The researchers are also interested in exploring whether bacteria play a causal role in the development of pain and fibromyalgia. And whether their presence could, eventually, help in finding a cure, as well as speed up the process of diagnosis.

Confirming a diagnosis and next steps towards finding a cure

Fibromyalgia is a disease that has proved difficult to diagnose. Patients can wait as long as 4 to 5 years to get a final diagnosis. But this may be about to change.

“We sorted through large amounts of data, identifying 19 species that were either increased or decreased in individuals with fibromyalgia,” says Emmanuel Gonzalez, from the Canadian Center for Computational Genomics and the Department of Human Genetics at McGill University. “By using machine learning, our computer was able to make a diagnosis of fibromyalgia, based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research, we hope to improve upon this accuracy, potentially creating a step-change in diagnosis.”

Amir Minerbi

Dr. Amir Minerbi, first author on the paper, along with his colleagues, have found a correlation between a disease involving chronic pain and alterations in the gut microbiome. CREDIT McGill University Health Centre

“People with fibromyalgia suffer not only from the symptoms of their disease but also from the difficulty of family, friends and medical teams to comprehend their symptoms,” says Yoram Shir, the senior author on the paper who is the Director of the Alan Edwards Pain Management Unit at the MUHC and an Associate Investigator from the BRaiN Program of the RI-MUHC. “As pain physicians, we are frustrated by our inability to help, and this frustration is a good fuel for research. This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain, and we really need new ways to look at chronic pain.”

How the research was done

The research was based on a cohort of 156 individuals in the Montreal area, 77 of whom suffer from fibromyalgia. Participants in the study were interviewed and gave stool, blood, saliva and urine samples, which were then compared with those of healthy control subjects, some of whom lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

The researchers’ next steps will be to see whether they get similar results in another cohort, perhaps in a different part of the world, and to do studies in animals to discover whether changes in bacteria play a role in the development of the disease.

Autism study suggests connection between repetitive behaviors, gut problems

Severity of GI symptoms, other autism symptoms also associated

In children with autism, repetitive behaviors and gastrointestinal problems may be connected, new research has found.

The study found that increased severity of other autism symptoms was also associated with more severe constipation, stomach pain and other gut difficulties.

The research, which appears in the journal Autism, found no association between social and communication difficulties and gastrointestinal symptoms.

The study doesn’t explain the biological mechanism for the relationship between repetitive behaviors, such as rocking back and forth and hand flapping, and gut problems. But it helps establish that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, a finding that could one day help lead to helpful interventions, said Payal Chakraborty, a graduate student in The Ohio State University College of Public Health who led the study.

Children with autism spectrum disorder are more likely than their typically developing peers to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities and abdominal pain. These symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with other autism spectrum disorder symptoms.

“In the general population, there’s a fair amount of evidence about the connection between mood and mental disorders and gastrointestinal difficulties. In autism, we wonder if the gut problems children experience are a core part of the disease itself or whether they’re brought on by other symptoms that children with autism experience,” Chakraborty said.

Chakraborty began the study as a student at Duke University, where she worked at the Center for Autism and Brain Development and became interested in the potential connection between the gut and other characteristics of the developmental disability.

Using data from a study designed to test the viability of cord blood transplants as an autism treatment, Chakraborty looked at detailed clinical measures and reports provided by the families of 176 children who were 2 to 7 years old to see if she could find any insights into the drivers of gastrointestinal problems. Almost all of the children, 93%, had at least one gastrointestinal symptom.

“GI problems are a significant issue for many people with autism and there’s evidence that these symptoms might exacerbate certain autism behaviors, which can lead to greater developmental challenges,” she said.

The specifics of the relationship are unclear, but it’s possible that repetitive behaviors in children with autism could be a coping mechanism that helps them manage their gastrointestinal discomfort, Chakraborty said, adding that the symptoms of autism often emerge at a time when children aren’t in a position to adequately communicate their physical suffering with words.

“Gastrointestinal problems are a major concern for many children with autism and we still have a lot to learn about the complicated gut/brain axis,” she said.


Children with and without multiple sclerosis have differences in gut bacteria

 

In a recent study, children with multiple sclerosis had differences in the abundance of specific gut bacteria than children without the disease. Certain types of bacteria were either more or less abundant in children with multiple sclerosis. In particular, there was an association between multiple sclerosis and an increase in gut bacteria that have been linked to inflammation and a decrease in gut bacteria that are considered anti-inflammatory.

A better understanding of gut bacteria’s role in multiple sclerosis may identify novel drug targets and pathways to improved health.

“While these findings are preliminary, they are intriguing. We also observed some similarities between our findings and other emerging gut microbiota studies in multiple sclerosis; whether these indicate a ‘gut signature’ of multiple sclerosis or of broader autoimmune disease remains to be determined,” said Professor Helen Tremlett, lead author of the European Journal of Neurology study. “We also found differences in the gut microbiota composition between those children taking a disease-modifying drug for their disease compared with those who were not. This finding warrants further study.”