Tag Archives: #microbiota

Fasting Lowers Blood Pressure by Reshaping the Gut Microbiota (Medicine)

Nearly half of adults in the United States have hypertension, a condition that raises the risk for heart disease and stroke, which are leading causes of death in the U. S.

At Baylor College of Medicine, Dr. David J. Durgan and his colleagues are dedicated to better understand hypertension, in particular the emerging evidence suggesting that disruption of the gut microbiota, known as gut dysbiosis, can have adverse effects on blood pressure.

“Previous studies from our lab have shown that the composition of the gut microbiota in animal models of hypertension, such as the SHRSP (spontaneously hypertensive stroke-prone) rat model, is different from that in animals with normal blood pressure,” said Durgan, assistant professor of anesthesiology at Baylor.

Dr. David Durgan © BCM

The researchers also have shown that transplanting dysbiotic gut microbiota from a hypertensive animal into a normotensive one (one having a healthy blood pressure)  results in the recipient developing high blood pressure.

“This result told us that gut dysbiosis is not just a consequence of hypertension, but is actually involved in causing it,” Durgan said. “This ground work led to the current study in which we proposed to answer two questions. First, can we manipulate the dysbiotic microbiota to either prevent or relieve hypertension? Second, how are the gut microbes influencing the animal’s blood pressure?”

Can manipulating the gut microbiota regulate blood pressure?

To answer the first question, Durgan and his colleagues drew on previous research showing that fasting was both one of the major drivers of the composition of the gut microbiota and a promoter of beneficial cardiovascular effects. These studies, however, had not provided evidence connecting the microbiota and blood pressure.

Working with the SHRSP model of spontaneous hypertension and normal rats, the researchers set up two groups. One group had SHRSP and normal rats that were fed every other day, while the other group, called control, had SHRSP and normal rats with unrestricted food availability.

Nine weeks after the experiment began, the researchers observed that, as expected, the rats in the SHRSP control had higher blood pressure than the normal control rats. Interestingly, in the group that fasted every other day, the SHRSP rats had significantly reduced blood pressure when compared with the SHRSP rats that had not fasted.

“Next, we investigated whether the microbiota was involved in the reduction of blood pressure we observed in the SHRSP rats that had fasted,” Durgan said.

The researchers transplanted the microbiota of the rats that had either fasted or fed without restrictions into germ-free rats, which have no microbiota of their own.

Durgan and his colleagues were excited to see that the germ-free rats that received the microbiota of normally fed SHRSP rats had higher blood pressure than the germ-free rats receiving microbiota from normal control rats, just like their corresponding microbiota donors.

“It was particularly interesting to see that the germ-free rats that received microbiota from the fasting SHRSP rats had significantly lower the blood pressure than the rats that had received microbiota from SHRSP control rats,” Durgan said.

These results demonstrated that the alterations to the microbiota induced by fasting were sufficient to mediate the blood pressure-lowering effect of intermittent fasting.”

Graphical abstract of this work. Image courtesy of the authors/Circulation Research, 2021
How the microbiota regulates blood pressure

The team proceeded to investigate the second question of their project. How does the gut microbiota regulate blood pressure?

“We applied whole genome shotgun sequence analysis of the microbiota as well as untargeted metabolomics analysis of plasma and gastrointestinal luminal content. Among the changes we observed, alterations in products of bile acid metabolism stood out as potential mediators of blood pressure regulation,” Durgan said.

The team discovered that the SHRSP hypertensive animals that were fed normally had lower bile acids in circulation than normotensive animals. On the other hand, SHRSP animals that followed an intermittent feeding schedule had more bile acids in the circulation.

“Supporting this finding, we found that supplementing animals with cholic acid, a primary bile acid, also significantly reduced blood pressure in the SHRSP model of hypertension,” Durgan said.

Taken together, the study shows for the first time that intermittent fasting can be beneficial in terms of reducing hypertension by reshaping the composition of gut microbiota in an animal model. The work also provides evidence that gut dysbiosis contributes to hypertension by altering bile acid signaling.

“This study is important to understand that fasting can have its effects on the host through microbiota manipulation,” Durgan said. “This is an attractive idea because it can potentially have clinical applications. Many of the bacteria in the gut microbiota are involved in the production of compounds that have been shown to have beneficial effects as they make it into the circulation and contribute to the regulation of the host’s physiology. Fasting schedules could one day help regulate the activity of gut microbial populations to naturally provide health benefits.”

Find all the details of this study in the journal Circulation Research.

Other contributors to this work include Huanan Shi, Bojun Zhang, Taylor Abo-Hamzy, James W. Nelson, Chandra Shekar R. Ambati, Joseph F. Petrosino and Robert M. Bryan, all at Baylor College of Medicine.

This work was supported by Public Health grants (RO1HL134838, R01NS102594 and DK56338), NIH grant P30DK056338, CPRIT Core Facility Support Award RP170005, NCI Cancer Center Support Grant P30CA125123, intramural funds from the Dan L. Duncan Cancer Center, and National Cancer Institute Cancer Center Support Grant P30CA125123.

Featured image: The human gastrointestinal tract is home of the gut microbiota, a large community of resident microorganisms known to influence host physiology in health and disease. Image credit: OpenClipart-Vectors


Reference: Huanan Shi, Bojun Zhang, Taylor Abo-Hamzy, James W Nelson, Chandra Shekar R Ambati, Joseph F Petrosino, Robert M Bryan, Jr., and David J Durgan, “Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure”, Circulation, 18 Feb 2021. https://doi.org/10.1161/CIRCRESAHA.120.318155


Provided by Baylor College Of Medicine

Pooping Out Miracles: Scientists Reveal Mechanism Behind Fecal Microbiota Transplantation (Medicine)

Osaka City University and IMSUT demonstrate fecal microbiota transplantation (FMT) success by revealing the coordinated effort of bacteriophages (phages) and their host bacteria in restoring human intestinal flora

In a study published in Gastroenterology – Researchers at Osaka City University and The Institute for Medical Science, The University of Tokyo(IMSUT), in collaboration with Brigham and Women’s Hospital in Boston, report the intestinal bacterial and viral metagenome information from the fecal samples of patients with recurrent Clostridioides difficile infection (rCDI). This comprehensive analysis reveals the bacteria and phages involved in pathogenesis in rCDI, and their remarkable pathways important for the recovery of intestinal flora function.

Clostridioides difficile infection (rCDI) occurs in the gut and is caused by the Gram-positive, spore-forming anaerobic bacterium, C. difficile when its spores attach to fecal matter and are transferred from hand to mouth by health care workers. Patients undergoing antibiotic treatment are especially susceptible as the microorganisms that maintain a healthy gut are greatly damaged by the antibiotics.

Treatment of rCDI involves withdrawing the causative antibiotics and initiating antibiotic therapy, although this can be very challenging. Fecal microbiota transplantation (FMT) is considered an effective alternative therapy as it addresses the issue from the ground up by replacing the damaged microflora with a healthy one through a stool transplant.

However, two deaths caused by antibiotic-resistant bacterial infections after FMT were reported in 2019, suggesting that a modification of FMT or alternatives are required to resolve safety concerns surrounding the treatment.

Researchers at Osaka City University and the Institute for Medical Science, University of Tokyo tackled this challenge head-on in a great study now published in Gastroenterology. 

Using their original analysis pipeline reported in 2020, the researchers obtained intestinal bacterial and viral metagenome information from the fecal samples of nine rCDI patients from Brigham and Women’s Hospital in Boston who successfully had an FMT. They revealed the bacteria and phages involved in the pathogenesis of rCDI and the remarkable pathways important for the recovery of intestinal flora function. 

By revealing how the bacteriome and virome in the intestine work together as an organ, the research team was able to show how FMT can be as safe as swapping out a bad organ with a good one.

“Intestinal microbiota should definitely be treated as an ‘organ’!” says principal investigator Professor Satoshi Uematsu, “FMT drastically changed the intestinal bacteriome and virome and is sure to restore the intestinal bacterial and viral functions.”

In the post-COVID-19 world, rCDI will become one of the more pressing international diseases. There is no doubt that FMT is an important therapeutic strategy for rCDI. “In addition to a variety of clinical surveys, comprehensive metagenomic analysis is very important in considering the safety of FMT.,” say Dr. Kosuke Fujimoto and Prof. Seiya Imoto.

This research was sponsored by the Takeda Science Foundation, the Canon Foundation and strategic programs for innovative research field 1 from Ministry of Education, Culture, Sports, Science and Technology of Japan, the Center of Innovation Program from Japan Science and Technology Agency. 

Featured image: Graphical abstract by Fujimoto et al.


Reference: Kosuke Fujimoto Yasumasa Kimura, Jessica R Allegretti, Mako Yamamoto, Yao-zhong Zhang, Kotoe Katayama, Georg Tremmel, Yunosuke Kawaguchi, Masaki Shimohigoshi, Tetsuya Hayashi, Miho Uematsu, Kiyoshi Yamaguchi, Yoichi Furukawa, Yutaka Akiyama, Rui Yamaguchi, Sheila E. Crowe, Peter B. Ernst, Satoru Miyano, Hiroshi Kiyono, Seiya Imoto and Satoshi Uematsu, “Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation”, Gastroenterology (IF=17.373). DOI:10.1053/j.gastro.2021.02.013
URL:https://www.gastrojournal.org/article/S0016-5085(21)00400-5/fulltext


Provided by University of Tokyo

Neanderthals Gut Microbiota And The Bacteria Helping Our Health (Biology)

Neanderthals’ gut microbiota already included some beneficial micro-organisms that are also found in our own intestine. An international research group led by the University of Bologna achieved this result by extracting and analysing ancient DNA from 50,000-year-old faecal sediments sampled at the archaeological site of El Salt, near Alicante (Spain).

Published in Communication Biology, their paper puts forward the hypothesis of the existence of ancestral components of human microbiota that have been living in the human gastrointestinal tract since before the separation between the Homo Sapiens and Neanderthals that occurred more than 700,000 years ago.

“These results allow us to understand which components of the human gut microbiota are essential for our health, as they are integral elements of our biology also from an evolutionary point of view” explains Marco Candela, the professor of the Department of Pharmacy and Biotechnology of the University of Bologna, who coordinated the study. “Nowadays there is a progressive reduction of our microbiota diversity due to the context of our modern life: this research group’s findings could guide us in devising diet- and lifestyle-tailored solutions to counteract this phenomenon”.

THE ISSUES OF THE “MODERN” MICROBIOTA

The gut microbiota is the collection of trillions of symbiont micro-organisms that populate our gastrointestinal tract. It represents an essential component of our biology and carries out important functions in our bodies, such as regulating our metabolism and immune system and protecting us from pathogenic micro-organisms.

Recent studies have shown how some features of modernity – such as the consumption of processed food, drug use, life in hyper-sanitized environments – lead to a critical reduction of biodiversity in the gut microbiota. This depletion is mainly due to the loss of a set of microorganisms referred to as “old friends”.

“The process of depletion of the gut microbiota in modern western urban populations could represent a significant wake-up call,” says Simone Rampelli, who is a researcher at the University of Bologna and first author of the study. “This depletion process would become particularly alarming if it involved the loss of those microbiota components that are crucial to our physiology”.

Indeed, there are some alarming signs. For example, in the West, we are witnessing a dramatic increase in cases of chronic inflammatory diseases, such as inflammatory bowel disease, metabolic syndrome, type 2 diabetes and colorectal cancer.

HOW THE “ANCIENT” MICROBIOTA CAN HELP

How can we identify the components of the gut microbiota that are more important for our health? And how can we protect them with targeted solutions? This was the starting point behind the idea of identifying the ancestral traits of our microbiota – i.e. the core of the human gut microbiota, which has remained consistent throughout our evolutionary history. Technology nowadays allows to successfully rise to this challenge thanks to a new scientific field, paleomicrobiology, which studies ancient microorganisms from archaeological remains through DNA sequencing.

The research group analysed ancient DNA samples collected in El Salt (Spain), a site where many Neanderthals lived. To be more precise, they analysed the ancient DNA extracted from 50,000 years old sedimentary faeces (the oldest sample of faecal material available to date). In this way, they managed to piece together the composition of the micro-organisms populating the intestine of Neanderthals. By comparing the composition of the Neanderthals’ microbiota to ours, many similarities aroused.

“Through the analysis of ancient DNA, we were able to isolate a core of microorganisms shared with modern Homo sapiens”, explains Silvia Turroni, researcher at the University of Bologna and first author of the study. “This finding allows us to state that these ancient micro-organisms populated the intestine of our species before the separation between Sapiens and Neanderthals, which occurred about 700,000 years ago”.

SAFEGUARDING THE MICROBIOTA

These ancestral components of the human gut microbiota include many well-known bacteria (among which Blautia, Dorea, Roseburia, Ruminococcus and Faecalibacterium) that are fundamental to our health. Indeed, by producing short-chain fatty acids from dietary fibre, these bacteria regulate our metabolic and immune balance. There is also the Bifidobacterium: a microorganism playing a key role in regulating our immune defences, especially in early childhood. Finally, in the Neanderthal gut microbiota, researchers identified some of those “old friends”. This confirms the researchers’ hypotheses about the ancestral nature of these components and their recent depletion in the human gut microbiota due to our modern life context.

“In the current modernization scenario, in which there is a progressive reduction of microbiota diversity, this information could guide integrated diet- and lifestyle-tailored strategies to safeguard the micro-organisms that are fundamental to our health”, concludes Candela. “To this end, promoting lifestyles that are sustainable for our gut microbiota is of the utmost importance, as it will help maintain the configurations that are compatible with our biology”.

Featured image: The research group analysed the ancient DNA extracted from 50,000 years old sedimentary faeces (the oldest sample of faecal material available to date). The samples were collected in El Salt (Spain), a site where many Neanderthals lived. © University of Bologna


Reference: Rampelli, S., Turroni, S., Mallol, C. et al. Components of a Neanderthal gut microbiome recovered from fecal sediments from El Salt. Commun Biol 4, 169 (2021). https://www.nature.com/articles/s42003-021-01689-y https://doi.org/10.1038/s42003-021-01689-y


Provided by University of Bologna

NIH Scientists Identify Nutrient That Helps Prevent Bacterial Infection (Medicine)

Taurine, which helps the body digest fats and oils, could offer treatment benefit.

WHAT:

Scientists studying the body’s natural defenses against bacterial infection have identified a nutrient–taurine–that helps the gut recall prior infections and kill invading bacteria, such as Klebsiella pneumoniae (Kpn). The finding, published in the journal Cell by scientists from five institutes of the National Institutes of Health, could aid efforts seeking alternatives to antibiotics.

Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil © NIAID

Scientists know that microbiota–the trillions of beneficial microbes living harmoniously inside our gut–can protect people from bacterial infections, but little is known about how they provide protection. Scientists are studying the microbiota with an eye to finding or enhancing natural treatments to replace antibiotics, which harm microbiota and become less effective as bacteria develop drug resistance.

The scientists observed that microbiota that had experienced prior infection and transferred to germ-free mice helped prevent infection with Kpn. They identified a class of bacteria–Deltaproteobacteria–involved in fighting these infections, and further analysis led them to identify taurine as the trigger for Deltaproteobacteria activity.

Taurine helps the body digest fats and oils and is found naturally in bile acids in the gut. The poisonous gas hydrogen sulfide is a byproduct of taurine. The scientists believe that low levels of taurine allow pathogens to colonize the gut, but high levels produce enough hydrogen sulfide to prevent colonization. During the study, the researchers realized that a single mild infection is sufficient to prepare the microbiota to resist subsequent infection, and that the liver and gallbladder–which synthesize and store bile acids containing taurine–can develop long-term infection protection.

The study found that taurine given to mice as a supplement in drinking water also prepared the microbiota to prevent infection. However, when mice drank water containing bismuth subsalicylate–a common over-the-counter drug used to treat diarrhea and upset stomach–infection protection waned because bismuth inhibits hydrogen sulfide production.

Scientists from NIH’s National Institute of Allergy and Infectious Diseases led the project in collaboration with researchers from the National Institute of General Medical Sciences; the National Cancer Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Human Genome Research Institute.

Reference: A Stacy et al. Infection trains the host for microbiota-enhanced resistance to pathogens. Cell
DOI: 10.1016/j.cell.2020.12.011 (2021).

Who

Yasmine Belkaid, Ph.D., chief of NIAID’s Metaorganism Immunity Section in the Laboratory of Immune System Biology, is available to comment.

This news release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process— each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research at NIH, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Gut Microbiota Plays a Role In Brain Function And Mood Regulation (Neuroscience)

Depression is a mental disorder that affects more than 264 million people of all ages worldwide. Understanding its mechanisms is vital for the development of effective therapeutic strategies. Scientists from the Institut Pasteur, Inserm and the CNRS recently conducted a study showing that an imbalance in the gut bacterial community can cause a reduction in some metabolites, resulting in depressive-like behaviors. These findings, which show that a healthy gut microbiota contributes to normal brain function, were published in Nature Communications on December 11, 2020.

Credit: Pascal Marseaud

The bacterial population in the gut, known as the gut microbiota, is the largest reservoir of bacteria in the body. Research has increasingly shown that the host and the gut microbiota are an excellent example of systems with mutually beneficial interactions. Recent observations also revealed a link between mood disorders and damage to the gut microbiota. This was demonstrated by a consortium of scientists from the Institut Pasteur, the CNRS and Inserm, who identified a correlation between the gut microbiota and the efficacy of fluoxetine, a molecule frequently used as an antidepressant. But some of the mechanisms governing depression, the leading cause of disability worldwide, remained unknown.

Using animal models, scientists recently discovered that a change to the gut microbiota brought about by chronic stress can lead to depressive-like behaviors, in particular by causing a reduction in lipid metabolites (small molecules resulting from metabolism) in the blood and the brain.

These lipid metabolites, known as endogenous cannabinoids (or endocannabinoids), coordinate a communication system in the body which is significantly hindered by the reduction in metabolites. Gut microbiota plays a role in brain function and mood regulation

Endocannabinoids bind to receptors that are also the main target of THC, the most widely known active component of cannabis. The scientists discovered that an absence of endocannabinoids in the hippocampus, a key brain region involved in the formation of memories and emotions, resulted in depressive-like behaviors.

The scientists obtained these results by studying the microbiotas of healthy animals and animals with mood disorders. As Pierre-Marie Lledo, Head of the Perception and Memory Unit at the Institut Pasteur (CNRS/Institut Pasteur) and joint last author of the study, explains: “Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviors in the latter.”

The scientists identified some bacterial species that are significantly reduced in animals with mood disorders. They then demonstrated that an oral treatment with the same bacteria restored normal levels of lipid derivatives, thereby alleviating the depressive-like behaviors. These bacteria could therefore serve as an antidepressant. Such treatments are known as “psychobiotics”.

“This discovery shows the role played by the gut microbiota in normal brain function,” continues Gérard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study. If there is an imbalance in the gut bacterial community, some lipids that are vital for brain function disappear, encouraging the emergence of depressive-like behaviors. In this particular case, the use of specific bacteria could be a promising method for restoring a healthy microbiota and treating mood disorders more effectively.

References: Grégoire Chevalier et al, Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system, Nature Communications (2020). DOI: 10.1038/s41467-020-19931-2

Provided by Pasteur Institute

When Strains of E.coli Play Rock-Paper-Scissors, It’s Not the Strongest That Survives (Biology)

New research from UC San Diego reveals hidden dynamics of bacteria colonies.

Bacteria is all around us—not just in bathrooms or kitchen counters, but also inside our bodies, including in tumors, where microbiota often flourish. These “small ecologies” can hold the key to cancer drug therapies and learning more about them can help development new life-saving treatments.

© UC San diego

What happens when different strains of bacteria are present in the same system? Do they co-exist? Do the strongest survive? In a microbial game of rock-paper-scissors, researchers at the University of California San Diego’s BioCircuits Institute uncovered a surprising answer. Their findings, titled “Survival of the weakest in non-transitive asymmetric interactions among strains of E. coli,” appeared in a recent edition of Nature Communications.

The research team consisted of Professor of Bioengineering and Molecular Biology Jeff Hasty; Michael Liao and Arianna Miano, both bioengineering graduate students; and Chloe Nguyen, a bioengineering undergraduate. They engineered three strains of E. coli (Escherichia coli) so that each strain produced a toxin that could kill one other strain, just like a game of rock-paper-scissors.

When asked how the experiment came about, Hasty commented, “In synthetic biology, complex gene circuits are typically characterized in bacteria that are growing in well-mixed liquid cultures. However, many applications involve cells that are restricted to grow on a surface. We wanted to understand the behavior of small engineered ecologies when the interacting species are growing in an environment that is closer to how bacteria are likely to colonize the human body.”

Diagram of engineered strains including one toxin and two immunity genes. Each toxin targets a different essential biological component of E.coli cells. Cr: BioCircuits Institute/UC San Diego

The researchers mixed the three populations together and let them grow on a dish for several weeks. When they checked back they noticed that, across multiple experiments, the same population would take over the entire surface—and it wasn’t the strongest (the strain with the most potent toxin). Curious about the possible reasons for this outcome, they devised an experiment to unveil the hidden dynamics at play.

There were two hypotheses: either the medium population (called “the enemy of the strongest” as the strain that the strongest would attack) would win or the weakest population would win. Their experiment showed that, surprisingly, the second hypothesis was true: the weakest population consistently took over the plate.

Going back to the rock-paper-scissor analogy, if we assume the “rock” strain of E.coli has the strongest toxin, it will quickly kill the “scissor” strain. Since the scissor strain was the only one able to kill the “paper” strain, the paper strain now has no enemies. It’s free to eat away at the rock strain slowly over a period of time, while the rock strain is unable to defend itself.

To make sense of the mechanism behind this phenomenon, the researchers also developed a mathematical model that could simulate fights between the three populations by starting from a wide variety of patterns and densities. The model was able to show how the bacteria behaved in multiple scenarios with common spatial patterns such as stripes, isolated clusters and concentric circles. Only when the strains were initially distributed in the pattern of concentric rings with the strongest in the middle, was it possible for the strongest strain to take over the plate.

It is estimated microbes outnumber human cells 10 to 1 in the human body and several diseases have been attributed to imbalances within various microbiomes. Imbalances within the gut microbiome have been linked to several metabolic and inflammatory disorders, cancer and even depression. The ability to engineer balanced ecosystems that can coexist for long periods of time may enable exciting new possibilities for synthetic biologists and new healthcare treatments. The research that Hasty’s group is conducting may help lay the foundation to one day engineer healthy synthetic microbiomes that can be used to deliver active compounds to treat various metabolic disorders or diseases and tumors.

Vice Chancellor for Research Sandra Brown said, “Bringing together molecular biology and bionengineering has allowed discovery with the potential to improve the health of people around the world. This is a discovery that may never have occurred if they weren’t working collaboratively. This is another testament to the power of UC San Diego’s multidisciplinary research.”

The BioCircuits Institute (BCI) is a multidisciplinary research unit that focuses on understanding the dynamic properties of biological regulatory circuits that span the scales of biology, from intracellular regulatory modules to population dynamics and organ function. BCI seeks to develop and validate theoretical and computational models to understand, predict and control complex biological functions. The institute is comprised of over 50 faculty from UC San Diego and other local institutions, including Scripps Research, the Salk Institute and the Sanford-Burnham Medical Research Institute.

This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health (grant R01-GM069811). Michael Liao is supported by the National Science Foundation Graduate Research Fellowship (grant DGE-1650112).

Reference: Michael J. Liao, Arianna Miano, Chloe B. Nguyen, Lin Chao, Jeff Hasty. Survival of the weakest in non-transitive asymmetric interactions among strains of E. coli. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-19963-8

Provided by UC San Diego

Researchers Suggest Stool Transplants Can Battle Serious Infections (Gastroenterology / Medicine)

Could number two be number one when it comes to combating recurrent Clostridium difficile (CDI) infections?

Using genetic material analysis and machine learning, UBC researchers have pinpointed several key factors to ensure successful fecal microbiota transplants (FMT), which have proven successful in treating bacterial infections in the gut including illnesses like C. difficile, Crohn’s Disease, Colitis and even obesity, explains lead author Negin Kazemian.

UBCO researchers Negin Kazemian and her supervisor, Assistant Professor Sepideh Pakpour, are investigating the internal dynamics of fecal matter donors and recipients to determine the effectiveness of the therapy. Credit: UBC Okanagan

“This therapy is still in its infancy, but studies like ours are helping identify key contributors to its overall success,” says Kazemian, a graduate student at UBC Okanagan’s School of Engineering.

Kazemian and her supervisor, Assistant Professor Sepideh Pakpour, are investigating the internal dynamics of both donors and recipients to set out a formula for the effectiveness of the therapy.

C. difficile is one of the most frequently identified health care-associated infection in North America, she adds. Once a patient gets it, the illness often recurs, making a significant negative impact on a patient’s gut microorganisms.

Kazemian explains that severely damaged gut ecosystems, like someone who has had C. difficile, are not self-renewing. Therefore, FMT can help by restoring damaged systems through the recreation of the original ecosystem, or the construction of an entirely new and alternative ecosystem.

“In our study, we showed that the success of gut ecological recovery through FMT is dependent on several factors, including the donor gut microbiome—the presence of specific bacteria—as well as the recipient’s pre-FMT gut community structures and the absence of specific bacteria and fungi.”

Some previous studies have pointed to the possibility of “super” donors, but these new findings indicate the relationship between donors and recipients is much more complex. Pakpour says the notion of the super-donor is oversimplified due to the observed short-term fluctuations. A recipient’s microbiota may be just as important to consider when predicting treatment outcomes, especially in unbalanced conditions such as ulcerative colitis.

“Take, for example, blood transplants where we have a strong understanding of the four main blood groups or types, and how they interact with one another,” says Pakpour. “With fecal transplants the research up to this point has not been as clear in what constitutes a good match or compatibility.”

Working with data from the University of Alberta Hospital, Kazemian and Pakpour analyzed the gut composition and DNA from samples extracted before and after FMT.

According to Kazemian, their findings indicate that there isn’t a “one stool fits all” approach to ensure transplant success.

“The data illustrates that the unique microorganisms in everyone’s bodies respond differently over time, and this has profound implications on whether these transplants work well or not.”

The researchers suggest that preparing donors and patients’ gut ecosystems prior to transplant, maybe by using metabolites, would potentially sync their microbiota leading the way to a higher probability of transplant success.

Reference: Negin Kazemian et al, The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome, Scientific Reports (2020). DOI: 10.1038/s41598-020-75162-x

Provided by University of British Columbia

The Gut Microbiota Forms A Molecule That Can Contribute To Diabetes Progression (Medicine)

It is the bacterial changes in the gut that increase the levels of imidazole propionate, the molecule that makes the body’s cells resistant to insulin in type 2 diabetes. This result emerges from a European study, MetaCardis.

©Gettyimages

The gut and its bacteria are considered important in many diseases and several studies have shown that the gut microbiota affects the breakdown of several different parts of our diet. In previous research on gut microbiota and type 2 diabetes, the focus has often been on butyric acid-producing dietary fibers and their possible effects on blood sugar regulation and insulin resistance.

In previous research led by Fredrik Bäckhed, Professor of molecular medicine at the University of Gothenburg, demonstrated that diabetes can be linked to a changes in the composition of intestinal bacteria, which increases the production of molecules that may contribute to the disease.

His group has shown that the altered intestinal microbiota leads to altered metabolism of the amino acid histidine, which in turn leads to increased production of imidazole propionate, the molecule that prevents the blood sugar lowering effects of insulin.

An article published in the journal Nature Communications now confirms the initial findings in a large European study with 1,990 subjects, which shows that patients with type 2 diabetes from Denmark, France and Germany also had increased levels of imidazole propionate in their blood.

“Our study clearly shows that imidazole propionate is elevated in type 2 diabetes in other populations as well” says Fredrik Bäckhed, and continues:

“The study also shows that the levels of imidazole propionate are elevated even before the diabetes diagnosis is established, in so-called prediabetes. This may indicate that imidazole propionate may contribute to disease progression.”

The altered gut microbiota observed in people with type 2 diabetes has fewer species than normal glucose tolerant individuals, which is also linked to other diseases. The researchers speculate that this leads to an altered metabolism of the amino acid histidine.

The EU-funded research collaboration MetaCardis has been led by Karine Clément, Professor of Nutrition at Sorbonne University and Assistance Publique Hôpitaux de Paris, a direction of an INSERM group in Paris.

“Interestingly enough, our findings suggest that it is the altered intestinal microbiota rather than the histidine intake in the diet that affects the levels of imidazole propionate”. She continuous:

“An unhealthy diet also associates with increased imidazole propionate in individuals with type 2 diabetes”.

One problem with research on microbiota and various diseases has been limited reproducibility. By studying the products that the bacteria produce, the metabolites, one focuses on the function of the bacteria rather than on the exact species in the intestine. Fredrik Bäckhed:

“The collaboration gave us unique opportunities to confirm preliminary findings that imidazole propionate can be linked to type 2 diabetes. Here we had the opportunity to analyze almost 2,000 samples and can thus determine that elevated levels of imidazole propionate can be linked to type 2 diabetes. As the levels are elevated even in prediabetes, imidazole propionate may also cause the disease in some cases, he says.

References: http://dx.doi.org/10.1038/s41467-020-19589-w

Provided by University of Gotherburg

Link Between Alzheimer’s Disease And Gut Microbiota Is Confirmed (Neuroscience)

Swiss and Italian scientists prove a correlation between gut microbiota and the appearance of amyloid plaques in the brain, typical of Alzheimer’s Disease.

Alzheimer’s disease is the most common cause of dementia. Still incurable, it directly affects nearly one million people in Europe, and indirectly millions of family members as well as society as a whole. In recent years, the scientific community has suspected that the gut microbiota plays a role in the development of the disease. A team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) in Switzerland, together with Italian colleagues from the National Research and Care Center for Alzheimer’s and Psychiatric Diseases Fatebenefratelli in Brescia, University of Naples and the IRCCS SDN Research Center in Naples, confirm the correlation, in humans, between an imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of the neurodegenerative disorders characteristic of Alzheimer’s disease. Proteins produced by certain intestinal bacteria, identified in the blood of patients, could indeed modify the interaction between the immune and the nervous systems and trigger the disease. These results, to be discovered in the Journal of Alzheimer’s Disease, make it possible to envisage new preventive strategies based on the modulation of the microbiota of people at risk.

The research laboratory of neurologist Giovanni Frisoni, director of the HUG Memory Centre and professor at the Department of Rehabilitation and Geriatrics of the UNIGE Faculty of Medicine, has been working for several years now on the potential influence of the gut microbiota on the brain, and more particularly on neurodegenerative diseases. «We have already shown that the gut microbiota composition in patients with Alzheimer’s disease was altered, compared to people who do not suffer from such disorders,» he explains. «Their microbiota has indeed a reduced microbial diversity, with an over-representation of certain bacteria and a strong decrease in other microbes. Furthermore, we have also discovered an association between an inflammatory phenomenon detected in the blood, certain intestinal bacteria and Alzheimer’s disease; hence the hypothesis that we wanted to test here: could inflammation in the blood be a mediator between the microbiota and the brain?

The brain under influence

Intestinal bacteria can influence the functioning of the brain and promote neurodegeneration through several pathways: they can indeed influence the regulation of the immune system and, consequently, can modify the interaction between the immune system and the nervous system. Lipopolysaccharides, a protein located on the membrane of bacteria with pro-inflammatory properties, have been found in amyloid plaques and around vessels in the brains of people with Alzheimer’s disease. In addition, the intestinal microbiota produces metabolites – in particular some short-chain fatty acids – which, having neuroprotective and anti-inflammatory properties, directly or indirectly affect brain function.

«To determine whether inflammation mediators and bacterial metabolites constitute a link between the gut microbiota and amyloid pathology in Alzheimer’s disease, we studied a cohort of 89 people between 65 and 85 years of age. Some suffered from Alzheimer’s disease or other neurodegenerative diseases causing similar memory problems, while others did not have any memory problems,» reports Moira Marizzoni, a researcher at the Fatebenefratelli Center in Brescia and first author of this work. «Using PET imaging, we measured their amyloid deposition and then quantified the presence in their blood of various inflammation markers and proteins produced by intestinal bacteria, such as lipopolysaccharides and short-chain fatty acids.»

A very clear correlation

«Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the quantity of amyloid plaques in the brain,» explains Moira Marizzoni. «Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology.»

This work thus provides proof of an association between certain proteins of the gut microbiota and cerebral amyloidosis through a blood inflammatory phenomenon. Scientists will now work to identify specific bacteria, or a group of bacteria, involved in this phenomenon.

A strategy based on prevention

This discovery paves the way for potentially highly innovative protective strategies – through the administration of a bacterial cocktail, for example, or of pre-biotics to feed the «good» bacteria in our intestine. «However, we shouldn’t be too quick to rejoice,» says Frisoni. «Indeed, we must first identify the strains of the cocktail. Then, a neuroprotective effect could only be effective at a very early stage of the disease, with a view to prevention rather than therapy. However, early diagnosis is still one of the main challenges in the management of neurodegenerative diseases, as protocols must be developed to identify high-risk individuals and treat them well before the appearance of detectable symptoms.» This study is also part of a broader prevention effort led by the UNIGE Faculty of Medicine and the HUG Memory Centre.

References: Marizzoni, Moira, et al., “Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease”, Journal of Alzheimer’s Disease, vol. 78, no. 2, pp. 683-697, 2020. Link: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200306 http://dx.doi.org/10.3233/JAD-200306

Provided by University of Geneve