Arquivo da tag: Microbiota

Interdisciplinary approach yields new insights into human evolution (Vanderbilt University)


Vanderbilt biologist Nicole Creanza Nicole Creanza takes interdisciplinary approach to human evolution as guest editor of Royal Society journal

The evolution of human biology should be considered part and parcel with the evolution of humanity itself, proposes Nicole Creanza, assistant professor of biological sciences. She is the guest editor of a new themed issue of the Philosophical Transactions of the Royal Society B, the oldest scientific journal in the world, that focuses on an interdisciplinary approach to human evolution.

Stanford professor Marc Feldman and Stanford postdoc Oren Kolodny collaborated with Creanza on the special issue.

“Within the blink of an eye on a geological timescale, humans advanced from using basic stone tools to examining the rocks on Mars; however, our exact evolutionary path and the relative importance of genetic and cultural evolution remain a mystery,” said Creanza, who specializes in the application of computational and theoretical approaches to human and cultural evolution, particularly language development. “Our cultural capacities-to create new ideas, to communicate and learn from one another, and to form vast social networks-together make us uniquely human, but the origins, the mechanisms, and the evolutionary impact of these capacities remain unknown.”

The special issue brings together researchers in biology, anthropology, archaeology, economics, psychology, computer science and more to explore the cultural forces affecting human evolution from a wider perspective than is usually taken.

“Researchers have begun to recognize that understanding non-genetic inheritance, including culture, ecology, the microbiome, and regulation of gene expression, is fundamental to fully comprehending evolution,” said Creanza. “It is essential to understand the dynamics of cultural inheritance at different temporal and spatial scales, to uncover the underlying mechanisms that drive these dynamics, and to shed light on their implications for our current theory of evolution as well as for our interpretation and predictions regarding human behavior.”

In addition to an essay discussing the need for an interdisciplinary approach to human evolution, Creanza included an interdisciplinary study of her own, examining the origins of English’s contribution to Sranan, a creole that emerged in Suriname following an influx of indentured servants from England in the 17th century.

Creanza, along with linguists Andre Sherriah and Hubert Devonish of the University of the West Indes and psychologist Ewart Thomas from Stanford, sought to determine the geographic origins of the English speakers whose regional dialects formed the backbone of Sranan. Their work combined linguistic, historical and genetic approaches to determine that the English speakers who influenced Sranan the most originated largely from two counties on opposite sides of southern England: Bristol, in the west, and Essex, in the east.

“Thus, analyzing the features of modern-day languages might give us new information about events in human history that left few other traces,” Creanza said.


How altered gut microbes cause obesity (Science Daily)

June 8, 2016
Yale University
Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines. But the mechanism has not been clear to date. In a new study, a team of researchers has identified how an altered gut microbiota causes obesity.

Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines. But the mechanism has not been clear. In a new study published in Nature, a Yale-led team of researchers has identified how an altered gut microbiota causes obesity.

In an earlier study, Gerald I. Shulman, M.D., the George R. Cowgill Professor of Medicine, observed that acetate, a short-chain fatty acid, stimulated the secretion of insulin in rodents. To learn more about acetate’s role, Shulman, who is also an investigator of the Howard Hughes Medical Institute, and a team of Yale researchers conducted a series of experiments in rodent models of obesity.

The research team compared acetate to other short-chain fatty acids and found higher levels of acetate in animals that consumed a high-fat diet. They also observed that infusions of acetate stimulated insulin secretion by beta cells in the pancreas, but it was unclear how.

Next, the researchers determined that when acetate was injected directly into the brain, it triggered increased insulin by activating the parasympathetic nervous system. “Acetate stimulates beta cells to secrete more insulin in response to glucose through a centrally mediated mechanism,” said Shulman. “It also stimulates secretion of the hormones gastrin and ghrelin, which lead to increased food intake.”

Finally, the research team sought to establish a causal relationship between the gut microbiota and increased insulin. After transferring fecal matter from one group of rodents to another, they observed similar changes in the gut microbiota, acetate levels, and insulin.

“Taken together these experiments demonstrate a causal link between alterations in the gut microbiota in response to changes in the diet and increased acetate production,” said Shulman. The increased acetate in turn leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he explained.

The study authors suggest that this positive feedback loop may have served an important role in evolution, by prompting animals to fatten up when they stumbled across calorically dense food in times of food scarcity.

“Alterations in the gut microbiota are associated with obesity and the metabolic syndrome in both humans and rodents,” Shulman noted. “In this study we provide a novel mechanism to explain this biological phenomenon in rodents, and we are now examining whether this mechanism translates to humans.”

Journal Reference:

  1. Rachel J. Perry, Liang Peng, Natasha A. Barry, Gary W. Cline, Dongyan Zhang, Rebecca L. Cardone, Kitt Falk Petersen, Richard G. Kibbey, Andrew L. Goodman, Gerald I. Shulman. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndromeNature, 2016; 534 (7606): 213 DOI: 10.1038/nature18309

New appreciation for human micro biome leads to greater understanding of human health (Science Daily)

Date: February 14, 2016

Source: University of Oklahoma

Summary: Anthropologists are studying the ancient and modern human micro biome and the role it plays in human health and disease. By applying genomic and proteomic sequencing technologies to ancient human microbiomes, such as coprolites and dental calculus, as well as to contemporary microbiomes in traditional and industrialized societies, Researchers are advancing the understanding of the evolutionary history of our microbial self and its impact on human health today.

University of Oklahoma anthropologists are studying the ancient and modern human microbiome and the role it plays in human health and disease. By applying genomic and proteomic sequencing technologies to ancient human microbiomes, such as coprolites and dental calculus, as well as to contemporary microbiomes in traditional and industrialized societies, OU researchers are advancing the understanding of the evolutionary history of our microbial self and its impact on human health today.

Christina Warinner, professor in the Department of Anthropology, OU College of Arts and Sciences, will present, “The Evolution and Ecology of Our Microbial Self,” during the American Association for the Advancement of Science panel on Evolutionary Biology Impacts on Medicine and Public Health, at 1:30 pm, Sunday, Feb. 14, 2016 in the Marriott Marshall Ballroom West, Washington, DC. Warinner will discuss how major events, such as the invention of agriculture and the advent of industrialization, have affected the human microbiome.

“We don’t have a complete picture of the microbiome,” Warinner said. “OU research indicates human behavior over the past 2000 years has impacted the gut microbiome. Microbial communities have become disturbed, but before we can improve our health, we have to understand our ancestral microbiome. We cannot make targeted or informed interventions until we know that. Ancient samples allow us to directly measure changes in the human microbiome at specific times and places in the past.”

Warinner and colleague, Cecil M. Lewis, Jr., co-direct OU’s Laboratories of Molecular Anthropology and Microbiome Research and the research focused on reconstructing the ancestral human oral and gut microbiome, addressing questions concerning how the relationship between humans and microbes has changed through time and how our microbiomes influence health and disease in diverse populations, both today and in the past. Warinner and Lewis are leaders in the field of paleogenomics, and the OU laboratories house the largest ancient DNA laboratory in the United States.

Warinner is pioneering the study of ancient human microbiomes, and in 2014 she published the first detailed metagenomics and metaproteomic characterization of the ancient oral microbiome in the journal Nature Genetics. In 2015, she published a study on the identification of milk proteins in ancient dental calculus and the reconstruction of prehistoric European dairying practices. In the same year, she was part of an international team that published the first South American hunter-gatherer gut microbiome and identified Treponema as a key missing ancestral microbe in industrialized societies.

Gut microbes signal to the brain when they’re full (Science Daily)

Date: November 24, 2015

Source: Cell Press

Summary: Don’t have room for dessert? The bacteria in your gut may be telling you something. Twenty minutes after a meal, gut microbes produce proteins that can suppress food intake in animals, reports a study. The researchers also show how these proteins injected into mice and rats act on the brain reducing appetite, suggesting that gut bacteria may help control when and how much we eat.

These are neurons (c-fos, green) in the rat central amygdala activated by E. coli proteins in stationary phase and surrounded by nerve terminals (calcitonin gene-related peptide, red) originating from anorexigenic brainstem projections. Credit: J. Breton, N. Lucas & D. Schapman.

Don’t have room for dessert? The bacteria in your gut may be telling you something. Twenty minutes after a meal, gut microbes produce proteins that can suppress food intake in animals, reports a study published November 24 in Cell Metabolism. The researchers also show how these proteins injected into mice and rats act on the brain reducing appetite, suggesting that gut bacteria may help control when and how much we eat.

The new evidence coexists with current models of appetite control, which involve hormones from the gut signalling to brain circuits when we’re hungry or done eating. The bacterial proteins–produced by mutualistic E. coli after they’ve been satiated–were found for the first time to influence the release of gut-brain signals (e.g., GLP-1 and PYY) as well as activate appetite-regulated neurons in the brain.

“There are so many studies now that look at microbiota composition in different pathological conditions but they do not explore the mechanisms behind these associations,” says senior study author Sergueï Fetissov of Rouen University and INSERM’s Nutrition, Gut & Brain Laboratory in France. “Our study shows that bacterial proteins from E. coli can be involved in the same molecular pathways that are used by the body to signal satiety, and now we need to know how an altered gut microbiome can affect this physiology.”

Mealtime brings an influx of nutrients to the bacteria in your gut. In response, they divide and replace any members lost in the development of stool. The study raises an interesting theory: since gut microbes depend on us for a place to live, it is to their advantage for populations to remain stable. It would make sense, then, if they had a way to communicate to the host when they’re not full, promoting host to ingest nutrients again.

In the laboratory, Fetissov and colleagues found that after 20 minutes of consuming nutrients and expanding numbers, E. coli bacteria from the gut produce different kinds of proteins than they did before their feeding. The 20 minute mark seemed to coincide with the amount of time it takes for a person to begin feeling full or tired after a meal. Excited over this discovery, the researcher began to profile the bacterial proteins pre- and post-feeding.

They saw that injection of small doses of the bacterial proteins produced after feeding reduced food intake in both hungry and free-fed rats and mice. Further analysis revealed that “full” bacterial proteins stimulated the release of peptide YY, a hormone associated with satiety, while “hungry” bacterial hormones did not. The opposite was true for glucagon-like peptide-1 (GLP-1), a hormone known to simulate insulin release.

The investigators next developed an assay that could detect the presence of one of the “full” bacterial proteins, called ClpB in animal blood. Although blood levels of the protein in mice and rats detected 20 minutes after meal consumption did not change, it correlated with ClpB DNA production in the gut, suggesting that it may link gut bacterial composition with the host control of appetite. The researchers also found that ClpB increased firing of neurons that reduce appetite. The role of other E.coli proteins in hunger and satiation, as well as how proteins from other species of bacteria may contribute, is still unknown.

“We now think bacteria physiologically participate in appetite regulation immediately after nutrient provision by multiplying and stimulating the release of satiety hormones from the gut,” Fetisov says. “In addition, we believe gut microbiota produce proteins that can be present in the blood longer term and modulate pathways in the brain.”

Journal Reference:

  1. Jonathan Breton, Naouel Tennoune, Nicolas Lucas, Marie Francois, Romain Legrand, Justine Jacquemot, Alexis Goichon, Charlène Guérin, Johann Peltier, Martine Pestel-Caron, Philippe Chan, David Vaudry, Jean-Claude do Rego, Fabienne Liénard, Luc Pénicaud, Xavier Fioramonti, Ivor S. Ebenezer, Tomas Hökfelt, Pierre Déchelotte, Sergueï O. Fetissov. Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial GrowthCell Metabolism, 2015; DOI: 10.1016/j.cmet.2015.10.017

Scientists call for national effort to understand and harness Earth’s microbes (Science Daily)

Berkeley Lab researchers co-author Science article proposing Unified Microbiome Initiative

October 29, 2015
DOE/Lawrence Berkeley National Laboratory
To understand and harness the capabilities of Earth’s microbial ecosystems, nearly fifty scientists propose a national effort in the US called the Unified Microbiome Initiative.

This colorized microscopy image hints at the complexity of microbial life. It shows two bacterial cells in soil. The bacteria glue clay particles together and protect themselves from predators. This also stabilizes soil and stores carbon that could otherwise enter the atmosphere. Credit: Manfred Auer, Berkeley Lab

Microbes are essential to life on Earth. They’re found in soil and water and inside the human gut. In fact, nearly every habitat and organism hosts a community of microbes, called a microbiome. What’s more, microbes hold tremendous promise for innovations in medicine, energy, agriculture, and understanding climate change.

Scientists have made great strides learning the functions of many microbes and microbiomes, but this research also highlights how much more there is to know about the connections between Earth’s microorganisms and a vast number of processes. Deciphering how microbes interact with each other, their hosts, and their environment could transform our understanding of the planet. It could also lead to new antibiotics, ways to fight obesity, drought-resistant crops, or next-gen biofuels, to name a few possibilities.

To understand and harness the capabilities of Earth’s microbial ecosystems, nearly fifty scientists from Department of Energy national laboratories, universities, and research institutions have proposed a national effort called the Unified Microbiome Initiative. The scientists call for the initiative in a policy forum entitled “A unified initiative to harness Earth’s microbiomes” published Oct. 30, 2015, in the journal Science.

The Unified Microbiome Initiative would involve many disciplines, including engineering, physical, life, and biomedical sciences; and collaborations between government institutions, private foundations, and industry. It would also entail the development of new tools that enable a mechanistic and predictive understanding of Earth’s microbial processes.

Among the authors of the Science article are several scientists from the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). These are Berkeley Lab Director Paul Alivisatos; Eoin Brodie, Deputy Director of the Climate and Ecosystem Sciences Division; Mary Maxon, the Biosciences Area Principal Deputy; Eddy Rubin, Director of the Joint Genome Institute; and Peidong Yang, a Faculty Scientist in the Materials Sciences Division. Alivisatos is also the Director of the Kavli Energy Nanoscience Institute, and Yang is the Co-Director.

Berkeley Lab has a long history of microbial research, from its pioneering work in metagenomics at the Joint Genome Institute, to the more recent Microbes to Biomes initiative, which is designed to harness microbes in ways that protect fuel and food supplies, environmental security, and health.

The call for the Unified Microbiome Initiative comes at a critical time in microbial research. DNA sequencing has enabled scientists to detect microbes in every biological system, thriving deep underground and inside insects for example, and in mind-boggling numbers: Earth’s microbes outnumber the stars in the universe. But to benefit from this knowledge, this descriptive phase must transition to a new phase that explores how microbial communities function, how to predict their actions, and how to make use of them.

“Technology has gotten us to the point where we realize that microbes are like dark matter in the universe. We know microbes are everywhere, and are far more complex than we previously thought, but we really need to understand how they communicate and relate to the environment,” says Brodie.

“And just like physicists are trying to understand dark matter, we need to understand the functions of microbes and their genes. We need to study what life is like at the scale of microbes, and how they relate to the planet,” Brodie adds.

This next phase of microbiome research will require strong ties between disciplines and institutions, and new technologies that accelerate discovery. The scientists map out several opportunities in the Science article. These include:

  • Tools to understand the biochemical functions of gene products, a large portion of which are unknown.
  • Technologies that quickly generate complete genomes from individual cells found in complex microbiomes.
  • Imaging capabilities that visualize individual microbes, along with their interactions and chemical products, in complex microbial networks.
  • Adaptive models that capture the complexity of interactions from molecules to microbes, and from microbial communities to ecosystems.

Many of these new technologies would be flexible platforms, designed initially for microbial research, but likely to find uses in other fields.

Ten years after the launch of the Unified Microbiome Initiative, the authors of the Science article envision an era in which a predictive understanding of microbial processes enables scientists to manage and design microbiomes in a responsible way–a key step toward harnessing their capabilities for beneficial applications.

“This is an incredibly exciting time to be involved in microbial research,” says Brodie. “It has the potential to contribute to so many advances, such as in medicine, energy, agriculture, biomanufacturing, and the environment.”

Journal Reference:

  1. A. P. Alivisatos, M. J. Blaser, E. L. Brodie, M. Chun, J. L. Dangl, T. J. Donohue, P. C. Dorrestein, J. A. Gilbert, J. L. Green, J. K. Jansson, R. Knight, M. E. Maxon, M. J. McFall-Ngai, J. F. Miller, K. S. Pollard, E. G. Ruby, S. A. Taha. A unified initiative to harness Earth’s microbiomesScience, 2015; 350 (6260): 507 DOI: 10.1126/science.aac8480

‘Nuvem personalizada’ de micróbios permite identificar indivíduos (Estadão)


22 Setembro 2015 | 19h 02

Experimento realizado por cientistas americanos revela que cada pessoa lança ao ar milhões de bactérias por hora, formando ao seu redor uma combinação única de microorganismos

Cada pessoa traz em torno de si uma “nuvem personalizada” de micróbios e, de acordo com um novo estudo, é possível identificar um indivíduo a partir do exame da combinação única de bactérias suspensas no ar ao seu redor.

O novo estudo, liderado por pesquisadores da Universidade do Oregon, nos Estados Unidos, foi publicado hoje na revista científica Peerj.

De acordo com o estudo, cada pessoa lança ao ar, a cada hora, milhões de bactérias diferentesDe acordo com o estudo, cada pessoa lança ao ar, a cada hora, milhões de bactérias diferentes

A fim de testar até que ponto seres humanos possuem uma assinatura própria em suas nuvens de micróbios, os cientistas realizaram um experimento de sequenciamento genético dos micróbios suspenso no ar em torno de 11 pessoas diferentes.

Os voluntários foram colocados em câmaras experimentais higienizadas e, a partir do exame dos micróbios coletados no ar, os pesquisadores puderam identificar a maior parte deles a partir de suas combinações pessoais de bactérias.

Os micróbios que permitiram identificar os indivíduos são bactérias extremamente comuns – como a Streptococcus, normalmente encontrada na boca, a Propionibacterium e a Corynebacterium, ambas abundantes na pele humana.

Ainda que todos os micróbios tenham sido detectados no ar em torno de todos os voluntários do estudo, os autores descobriram que diferentes combinações das bactérias permitiam distinguir indivíduos.

“Nós já esperávamos que poderíamos detectar o conjunto de micróbios no ar em torno de uma pessoa, mas ficamos surpresos ao descobrir que podemos identificar a maior parte dos ocupantes das câmaras unicamente a partir de amostras de suas nuvens de micróbios”, disse o autor principal do estudo, James Meadow, pós-doutorando da Universidade do Oregon.

“Nossos resultados confirmam que um espaço ocupado é microbioticamente distinto de um espaço desocupado. Demonstramos também pela primeira vez que indivíduos emitem sua própria nuvem de micróbios personalizada”, afirmou Meadow.

“Aura” de micróbios. Durante o experimento, os voluntários receberam roupas limpas e foram isolados em uma câmara estéril, onde ficaram sentados em uma cadeira de plástico desinfetada por até quatro horas. As amostras das bactérias emitidas pelos indivíduos foi feita a partir de material coletado em placas de Petri – pequenos pratos de vidro usados em laboratório para culturas de bactérias – deixadas na câmara e em filtros de ar especiais.

Segundo Meadow, o exame do material deixou claro que cada voluntário emitiu milhões e milhões de micróbios pela respiração, pela pele e provavelmente pelo suor. Os cientistas verificaram que a combinação de bactérias de cada indivíduo era totalmente distinta.

O estudo, segundo os autores, ajuda a compreender até que ponto as pessoas emitem sua população específica de micróbios no ambiente ao redor e pode ajudar a entender os mecanismos envolvidos no alastramento de doenças infecciosas em prédios.

A descoberta pode ter também, de acordo com os autores, aplicações forenses como determinar onde uma pessoa esteve, embora ainda não tenha ficado claro se indivíduos podem ser detectados em um grupo com muitas pessoas.

Small advances: understanding the micro biome (ABC RN)

Tuesday 1 September 2015 4:27PM

Amanda Smith



What is it that makes you, you? While you’re made up of 10 trillion human cells, 100 trillion microbial cells also live on you and in you. This vast array of microscopic bugs may be your defining feature, and scientists around the world are racing to find out more. Amanda Smith reports.


Microbes, it seems, are the next big thing. Around the world, scientists are researching the human microbiome—the genes of our microbes—in the hope of unlocking quite a different way to understand sickness and health.

At the Microbiome Initiative at the University of California, San Diego, Rob Knight runs the American Gut Project, a citizen science initiative where you can get your microbiome sequenced.

Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches.


‘What we can do right now is put you on this microbial map, where we can compare your microbes to the microbes of thousands of other people we’ve already looked at,’ he says. ‘But what we need to do is develop more of a microbial GPS that doesn’t just tell you where you are, but tells you where you want to go and what you need to do, step by step, in order to get there.’

The Australian Centre for Ecogenomics is also setting up a service where you can get your gut microbes analysed. The centre’s director, Phillip Hugenholtz, predicts that in years to come such a process will be a diagnostic procedure when you go to the doctor, much like getting a blood test.

‘I definitely think that’s going to become a standard part of your personalised medicine’, he says. ‘Micro-organisms are sometimes a very good early indicator of things occurring in your body and so it will become something that you’d go and get done maybe once or twice a year to see what’s going on.’

While this level of interest in the microbiome is new, the first person to realise we’re all teeming with micro-organisms was Dutchman Anton Leeuwenhoek, way back in 1676. Leeuwenhoek was interested in making lenses, and constructed himself a microscope.

‘He was looking at the scum from his teeth, and was amazed to see in this scraped-off plaque from inside his own mouth what he called hundreds of different “animalcules swimming a-prettily”,’ says Tim Spector, professor of genetic epidemiology at Kings College London.

‘He was the first to describe this, and it took hundreds of years before people actually believed that we were completely full of these microbes and we’d co-evolved with them.’

Microbes have come a long way over the last century. Until recent advances in DNA sequencing, all tummy bugs were considered bad.

‘We used to think that there was no such thing as a good microbe in our guts, that they were all out to do us no good, and we’ve basically spent the last 100 years trying to eliminate them with disinfectants and then the last 50 years with antibiotics,’ says Spector.

This has given rise to the ‘hygiene hypothesis’, which contends that by keeping ourselves too clean, we’re denying ourselves the microbes necessary to keep our immune system balanced, resulting in all sorts of chronic diseases.

‘Over the last half-century, as infectious diseases like polio and measles and hepatitis and so-on have plummeted in their frequency, chronic diseases—everything from obesity to diabetes to inflammatory bowel disease—have been skyrocketing,’ says the Microbiome Initiative’s Rob Knight.

‘So the idea is that potentially without exposure to a diverse range of healthy microbes our immune systems might be going into overdrive and attacking our own cells, or overreacting to harmless things we find in the environment.’

Antonie van Leeuwenhoek


In terms of human DNA, we’re all 99.99 per cent identical. However our microbial profiles can differ enormously. We might share just 10 per cent of our dominant microbial species with others.

According to Knight, some of the differences are explained by method of birth.

‘If you come out the regular way you get coated with microbes as you’re passing through your mother’s birth canal,’ he says.

Babies delivered by Caesarian section, on the other hand, have microbes that are mostly found on adult skin, from being touched by different doctors and nurses.

‘One thing that’s potentially interesting about that is differences between C-section and vaginally delivered babies have been reported: higher rates in C-section babies of asthma, allergies, atopic disease, even obesity. All of those have been linked to the microbiome now.’

Also important to the development of healthy microbiota in babies is breastfeeding, according to Maureen Minchin, the author of Milk Matters.

‘We’ve known for over 100 years that breast milk and formula result in very, very different gut flora in babies, but it’s only very recently that anyone has thought to look and see what breast milk does contain, and at last count there were well over 700 species of bacteria in breast milk,’ she says.

According to Minchin, breastfeeding is the bridge between the womb and the world for babies.

‘Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches. Her microbiome is present in that breast milk and will help create the appropriate microbiome in the baby.’

Minchin is an advocate of the World Health Organisation’s recommendation to breastfeed exclusively to six months and then continue breastfeeding while introducing other foods through the first and second year.

Related: Why the digestive system and its bacteria are a ‘second brain’

So if what babies are fed is important for their microbiome, what about adults? Tim Spector says research into microbes is yielding new information about healthy eating.

‘It’s going to soon revolutionise how we look at food and diet. This is one of the most exciting things in science at the moment, because it’s obviously much easier to change your microbes than it is to change your genes.’

‘Most processed foods only contain about five ingredients, and in a way our epidemic of the last 30 years of obesity and allergy is that our diets have become less and less diverse.’

According to Spector, studies of people with various chronic diseases, obesity and diabetes show a common feature, which is that their gut microbes have a much-reduced diversity compared to healthy people.

He likes to use the analogy of a garden: ‘A neglected garden has very few species, not much fertilised soil, and this allows weeds to take over in great numbers,’ he says.

‘I think this is a nice concept because we’re very good gardeners, humans, and I think we need to start using those principles—fertilising, adding soil, experimenting and avoiding adding nasty toxins to our own bodies as we would our gardens.’

May your gut flora bloom!

Micro biomes of human throat may be linked to schizophrenia (Science Daily)

Studying microbiomes in throat may help identify causes and treatments of brain disorder

August 25, 2015
George Washington University
In the most comprehensive study to date, researchers have identified a potential link between microbes (viruses, bacteria and fungi) in the throat and schizophrenia. This link may offer a way to identify causes and develop treatments of the disease and lead to new diagnostic tests.

In the most comprehensive study to date, researchers at the George Washington University have identified a potential link between microbes (viruses, bacteria and fungi) in the throat and schizophrenia. This link may offer a way to identify causes and develop treatments of the disease and lead to new diagnostic tests.

“The oropharynx of schizophrenics seems to harbor different proportions of oral bacteria than healthy individuals,” said Eduardo Castro-Nallar, a Ph.D. candidate at GW’s Computational Biology Institute (CBI) and lead author of the study. “Specifically, our analyses revealed an association between microbes such as lactic-acid bacteria and schizophrenics.”

Recent studies have shown that microbiomes — the communities of microbes living within our bodies — can affect the immune system and may be connected to mental health. Research linking immune disorders and schizophrenia has also been published, and this study furthers the possibility that shifts in oral communities are associated with schizophrenia.

Mr. Castro-Nallar’s research sought to identify microbes associated with schizophrenia, as well as components that may be associated with or contribute to changes in the immune state of the person. In this study, the group found a significant difference in the microbiomes of healthy and schizophrenic patients.

“Our results suggesting a link between microbiome diversity and schizophrenia require replication and expansion to a broader number of individuals for further validation,” said Keith Crandall, director of the CBI and contributing author of the study. “But the results are quite intriguing and suggest potential applications of biomarkers for diagnosis of schizophrenia and important metabolic pathways associated with the disease.”

The study helps to identify possible contributing factors to schizophrenia. With additional studies, researchers may be able to determine if microbiome changes are a contributing factor to schizophrenia, are a result of schizophrenia or do not have a connection to the disorder.

Journal Reference:

  1. Eduardo Castro-Nallar, Matthew L. Bendall, Marcos Pérez-Losada, Sarven Sabuncyan, Emily G. Severance, Faith B. Dickerson, Jennifer R. Schroeder, Robert H. Yolken, Keith A. Crandall. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controlsPeer J, August 25th, 2015 [link]

Can the Bacteria in Your Gut Explain Your Mood? (New York Times)

Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician. Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.

Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.

Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’’

Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’

Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.

At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment. The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.

When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.

In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)

For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.

Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’ The results suggested that the bacteria were somehow altering the neural chemistry of mice.

Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’

It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.

By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.

To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.

Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.

Credit: Illustration by Andrew Rae 

Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’

Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit take.

‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’

Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.

But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.

Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.

Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student at his lab and now a neuroscientist at Caltech, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.

The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’

Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.

The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’

Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’

If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’

The Surprising Link Between Gut Bacteria And Anxiety (Huff Post)

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Posted: 01/04/2015 10:05 am EST 


In recent years, neuroscientists have become increasingly interested in the idea that there may be a powerful link between the human brain and gut bacteria. And while a growing body of research has provided evidence of the brain-gut connection, most of these studies so far have been conducted on animals.

Now, promising new research from neurobiologists at Oxford University offers some preliminary evidence of a connection between gut bacteria and mental health in humans. The researchers found that supplements designed to boost healthy bacteria in the gastrointestinal tract (“prebiotics”) may have an anti-anxiety effect insofar as they alter the way that people process emotional information.

While probiotics consist of strains of good bacteria, prebiotics are carbohydrates that act as nourishment for those bacteria. With increasing evidence that gut bacteria may exert some influence on brain function and mental health, probiotics and prebiotics are being increasingly studied for the potential alleviation of anxiety and depression symptoms.

“Prebiotics are dietary fibers (short chains of sugar molecules) that good bacteria break down, and use to multiply,” the study’s lead author, Oxford psychiatrist and neurobiologist Dr. Philip Burnet, told The Huffington Post. “Prebiotics are ‘food’ for good bacteria already present in the gut. Taking prebiotics therefore increases the numbers of all species of good bacteria in the gut, which will theoretically have greater beneficial effects than [introducing] a single species.”

To test the efficacy of prebiotics in reducing anxiety, the researchers asked 45 healthy adults between the ages of 18 and 45 to take either a prebiotic or a placebo every day for three weeks. After the three weeks had passed, the researchers completed several computer tests assessing how they processed emotional information, such as positive and negatively-charged words.

The results of one of the tests revealed that subjects who had taken the prebiotic paid less attention to negative information and more attention to positive information, compared to the placebo group, suggesting that the prebiotic group had less anxiety when confronted with negative stimuli. This effect is similar to that which has been observed among individuals who have taken antidepressants or anti-anxiety medication.

The researchers also found that the subjects who took the prebiotics had lower levels of cortisol — a stress hormone which has been linked with anxiety and depression — in their saliva when they woke up in the morning.

While previous research has documented that altering gut bacteria has a similarly anxiety-reducing effect in mice, the new study is one of the first to examine this phenomenon in humans. As of now, research on humans is in its early stages. A study conducted last year at UCLA found that women who consumed probiotics through regularly eating yogurt exhibited altered brain function in both a resting state and when performing an emotion-recognition task.

“Time and time again, we hear from patients that they never felt depressed or anxious until they started experiencing problems with their gut,” Dr. Kirsten Tillisch, the study’s lead author, said in a statement. “Our study shows that the gut–brain connection is a two-way street.”

So are we moving towards a future in which mental illness may be able to be treated (or at least managed) using targeted probiotic cocktails? Burnet says it’s possible, although they’re unlikely to replace conventional treatment.

“I think pre/probiotics will only be used as ‘adjuncts’ to conventional treatments, and never as mono-therapies,” Burnet tells HuffPost. “It is likely that these compounds will help to manage mental illness… they may also be used when there are metabolic and/or nutritional complications in mental illness, which may be caused by long-term use of current drugs.”

The findings were published in the journal Psychopharmacology.

Gut microbiota influences blood-brain barrier permeability (Science Daily)

Date: November 19, 2014

Source: Karolinska Institutet

Summary: Our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood, a new study in mice shows. The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream.

Uptake of the substance Raclopride in the brain of germ-free versus conventional mice. Credit: Miklos Toth

A new study in mice, conducted by researchers at Sweden’s Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.

The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes — which therefore play an important role in the protection of the brain.

The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

“We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus,” says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. “In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma.”

The team also showed that the increased ‘leakiness’ of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this ‘leakiness’ could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.

“These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology,” says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier.”

Journal Reference:

  1. V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, N. Bakocevic, N. L. Guan, P. Kundu, B. Gulyas, C. Halldin, K. Hultenby, H. Nilsson, H. Hebert, B. T. Volpe, B. Diamond, S. Pettersson. The gut microbiota influences blood-brain barrier permeability in miceScience Translational Medicine, 2014; 6 (263): 263ra158 DOI: 10.1126/scitranslmed.3009759

How the bacteria in our gut affect our cravings for food (Conversation)

November 6 2014, 10.00pm EST

Vincent Ho

Gut bacteria can manufacture special proteins that are very similar to hunger-regulating hormones. Lighthunter/Shutterstock

We’ve long known that that the gut is responsible for digesting food and expelling the waste. More recently, we realised the gut has many more important functions and acts a type of mini-brain, affecting our mood and appetite. Now, new research suggests it might also play a role in our cravings for certain types of food.

How does the mini-brain work?

The gut mini-brain produces a wide range of hormones and contains many of the same neurotransmitters as the brain. The gut also contains neurons that are located in the walls of the gut in a distributed network known as the enteric nervous system. In fact, there are more of these neurons in the gut than in the entire spinal cord.

The enteric nervous system communicates to the brain via the brain-gut axis and signals flow in both directions. The brain-gut axis is thought to be involved in many regular functions and systems within the healthy body, including the regulation of eating.

Let’s consider what happens to the brain-gut axis when we eat a meal. When food arrives in the stomach, certain gut hormones are secreted. These activate signalling pathways from the gut to the brainstem and the hypothalamus to stop food consumption. Such hormones include the appetite-suppressing hormones peptide YY and cholecystokinin.

Gut hormones can bind and activate receptor targets in the brain directly but there is strong evidence that the vagus nerve plays a major role in brain-gut signalling. The vagus nerve acts as a major highway in the brain-gut axis, connecting the over 100 million neurons in the enteric nervous system to the medulla (located at the base of the brain).

Research has shown that vagus nerve blockade can lead to marked weight loss, while vagus nerve stimulation is known to trigger excessive eating in rats.

This brings us to the topic of food cravings. Scientists have largely debunked the myth that food cravings are our bodies’ way of letting us know that we need a specific type of nutrient. Instead, an emerging body of research suggests that our food cravings may actually be significantly shaped by the bacteria that we have inside our gut. In order to explore this further we will cover the role of gut microbes.

Gut microbiota

As many as 90% of our cells are bacterial. In fact, bacterial genes outnumber human genes by a factor of 100 to one.

The gut is an immensely complex microbial ecosystem with many different species of bacteria, some of which can live in an oxygen-free environment. An average person has approximately 1.5 kilograms of gut bacteria. The term “gut microbiota” is used to describe the bacterial collective.

We each have around 1.5kg of bacteria in our guts. Christopher PooleyCC BY

Gut microbiota send signals to the brain via the brain-gut axis and can have dramatic effects on animal behaviour and health.

In one study, for example, mice that were genetically predisposed to obesity remained lean when they were raised in a sterile environment without gut microbiota. These germ-free mice were, however, transformed into obese mice when fed a faecal pellet that came from an obese mouse raised conventionally.

The role of gut microbiota in food cravings

There is growing evidence to support the role of gut microbiota in influencing why we crave certain foods.

We know that mice that are bred in germ-free environments prefer more sweets and have greater number of sweet taste receptors in their gut compared to normal mice. Research has also found that persons who are “chocolate desiring” have microbial breakdown products in their urine that are different from those of “chocolate indifferent individuals” despite eating identical diets.

Many gut bacteria can manufacture special proteins (called peptides) that are very similar to hormones such as peptide YY and ghrelin that regulate hunger. Humans and other animals have produced antibodies against these peptides. This raises the distinct possibility that microbes might be able to directly influence human eating behaviour through their peptides that mimic hunger-regulating hormones or indirectly through antibodies that can interfere with appetite regulation.

Practical implications

There are substantial challenges to overcome before we can apply this knowledge about gut microbiota in a practical sense.

First, there is the challenge of collecting the gut microbes. Traditionally this is collected from stools but gut microbiota is known to vary between different regions of the gut, such as the small intestine and colon. Obtaining bacterial tissue through endoscopy or another invasive collection technique in addition to stool samples may lead to more accurate representation of the gut microbiome.

Second, the type of sequencing that is currently used for gut microbiota screening is expensive and time-consuming. Advances will need to be made before this technology is in routine use.

Probably the greatest challenge in gut microbiota research is the establishment of a strong correlation between gut microbiota patterns and human disease. The science of gut microbiota is in its infancy and there needs to be much more research mapping out disease relationships.

Probiotics contain live microorganisms. Quanthem/Shutterstock

But there is reason to be hopeful. There is now strong interest in utilising both prebiotics and probiotics to alter our gut micro biome. Prebiotics are non-digestible carbohydrates that trigger the growth of beneficial gut bacteria, while probiotics are beneficial live microorganisms contained in foods and supplements.

Faecal transplantation is also now an accepted treatment for those patients that have a severe form of gut bacterial infection called Clostridium difficile, which has been unresponsive to antibiotics.

The use of such targeted strategies is likely to become increasingly common as we better understand how gut microbiota influence our bodily functions, including food cravings.

Our Microbiome May Be Looking Out for Itself (New York Times)

A highly magnified view of Enterococcus faecalis, a bacterium that lives in the human gut. Microbes may affect our cravings, new research suggests.CreditCenters for Disease Control and Prevention

Your body is home to about 100 trillion bacteria and other microbes, collectively known as your microbiome. Naturalists first became aware of our invisible lodgers in the 1600s, but it wasn’t until the past few years that we’ve become really familiar with them.

This recent research has given the microbiome a cuddly kind of fame. We’ve come to appreciate how beneficial our microbes are — breaking down our food, fighting off infections and nurturing our immune system. It’s a lovely, invisible garden we should be tending for our own well-being.

But in the journal Bioessays, a team of scientists has raised a creepier possibility. Perhaps our menagerie of germs is also influencing our behavior in order to advance its own evolutionary success — giving us cravings for certain foods, for example.

Maybe the microbiome is our puppet master.

“One of the ways we started thinking about this was in a crime-novel perspective,” said Carlo C. Maley, an evolutionary biologist at the University of California, San Francisco, and a co-author of the new paper. “What are the means, motives and opportunity for the microbes to manipulate us? They have all three.”

The idea that a simple organism could control a complex animal may sound like science fiction. In fact, there are many well-documented examples of parasites controlling their hosts.

Some species of fungi, for example, infiltrate the brains of ants and coax them to climb plants and clamp onto the underside of leaves. The fungi then sprout out of the ants and send spores showering onto uninfected ants below.

How parasites control their hosts remains mysterious. But it looks as if they release molecules that directly or indirectly can influence their brains.

Our microbiome has the biochemical potential to do the same thing. In our guts, bacteria make some of the same chemicals that our neurons use to communicate with one another, such as dopamine and serotonin. And the microbes can deliver these neurological molecules to the dense web of nerve endings that line the gastrointestinal tract.

A number of recent studies have shown that gut bacteria can use these signals to alter the biochemistry of the brain. Compared with ordinary mice, those raised free of germs behave differently in a number of ways. They are more anxious, for example, and have impaired memory.

Adding certain species of bacteria to a normal mouse’s microbiome can reveal other ways in which they can influence behavior. Some bacteria lower stress levels in the mouse. When scientists sever the nerve relaying signals from the gut to the brain, this stress-reducing effect disappears.

Some experiments suggest that bacteria also can influence the way their hosts eat. Germ-free mice develop more receptors for sweet flavors in their intestines, for example. They also prefer to drink sweeter drinks than normal mice do.

Scientists have also found that bacteria can alter levels of hormones that govern appetite in mice.

Dr. Maley and his colleagues argue that our eating habits create a strong motive for microbes to manipulate us. “From the microbe’s perspective, what we eat is a matter of life and death,” Dr. Maley said.

Different species of microbes thrive on different kinds of food. If they can prompt us to eat more of the food they depend on, they can multiply.

Microbial manipulations might fill in some of the puzzling holes in our understandings about food cravings, Dr. Maley said. Scientists have tried to explain food cravings as the body’s way to build up a supply of nutrients after deprivation, or as addictions, much like those for drugs like tobacco and cocaine.

But both explanations fall short. Take chocolate: Many people crave it fiercely, but it isn’t an essential nutrient. And chocolate doesn’t drive people to increase their dose to get the same high. “You don’t need more chocolate at every sitting to enjoy it,” Dr. Maley said.

Perhaps, he suggests, the certain kinds of bacteria that thrive on chocolate are coaxing us to feed them.

John F. Cryan, a neuroscientist at University College Cork in Ireland who was not involved in the new study, suggested that microbes might also manipulate us in ways that benefited both them and us. “It’s probably not a simple parasitic scenario,” he said.

Research by Dr. Cryan and others suggests that a healthy microbiome helps mammals develop socially. Germ-free mice, for example, tend to avoid contact with other mice.

That social bonding is good for the mammals. But it may also be good for the bacteria.

“When mammals are in social groups, they’re more likely to pass on microbes from one to the other,” Dr. Cryan said.

“I think it’s a very interesting and compelling idea,” said Rob Knight, a microbiologist at the University of Colorado, who was also not involved in the new study.

If microbes do in fact manipulate us, Dr. Knight said, we might be able to manipulate them for our own benefit — for example, by eating yogurt laced with bacteria that would make us crave healthy foods.

“It would obviously be of tremendous practical importance,” Dr. Knight said. But he warned that research on the microbiome’s effects on behavior was “still in its early stages.”

The most important thing to do now, Dr. Knight and other scientists said, was to run experiments to see if microbes really are manipulating us.

Mark Lyte, a microbiologist at the Texas Tech University Health Sciences Center who pioneered this line of research in the 1990s, is now conducting some of those experiments. He’s investigating whether particular species of bacteria can change the preferences mice have for certain foods.

“This is not a for-sure thing,” Dr. Lyte said. “It needs scientific, hard-core demonstration.”

Wild sheep show benefits of putting up with parasites (Science Daily)

Date: August 7, 2014

Source: Princeton University

Summary: In the first evidence that natural selection favors an individual’s infection tolerance, researchers have found that an animal’s ability to endure an internal parasite strongly influences its reproductive success. The finding could provide the groundwork for boosting the resilience of humans and livestock to infection.

The researchers examined the relationship between each sheep’s body weight and its level of infection by nematodes, tiny parasitic worms that thrive in the gastrointestinal tract of sheep. This scanning electron micrograph shows nematodes on the surface of a sheep’s gut with a field of view of approximately one centimeter. An economic detriment to sheep farmers, nematodes infect both wild and domesticated sheep, resulting in weight loss, reduced wool growth and death. Credit: Photo by David Smith/Moredun Research Institute

In the first evidence that natural selection favors an individual’s infection tolerance, researchers from Princeton University and the University of Edinburgh have found that an animal’s ability to endure an internal parasite strongly influences its reproductive success. Reported in the journalPLoS Biology, the finding could provide the groundwork for boosting the resilience of humans and livestock to infection.

The researchers used 25 years of data on a population of wild sheep living on an island in northwest Scotland to assess the evolutionary importance of infection tolerance. They first examined the relationship between each sheep’s body weight and its level of infection with nematodes, tiny parasitic worms that thrive in the gastrointestinal tract of sheep. The level of infection was determined by the number of nematode eggs per gram of the animal’s feces.

While all of the animals lost weight as a result of nematode infection, the degree of weight loss varied widely: an adult female sheep with the maximum egg count of 2,000 eggs per gram of feces might lose as little as 2 percent or as much as 20 percent of her body weight. The researchers then tracked the number of offspring produced by each of nearly 2,500 sheep and found that sheep with the highest tolerance to nematode infection produced the most offspring, while sheep with lower parasite tolerance left fewer descendants.

To measure individual differences in parasite tolerance, the researchers used statistical methods that could be extended to studies of disease epidemiology in humans, said senior author Andrea Graham, an assistant professor of ecology and evolutionary biology at Princeton. Medical researchers have long understood that people with similar levels of parasite infection can experience very different symptoms. But biologists are just beginning to appreciate the evolutionary importance of this individual variation.

“For a long time, people assumed that if you knew an individual’s parasite burden, you could perfectly predict its health and survival prospects,” Graham said. “More recently, evolutionary biologists have come to realize that’s not the case, and so have developed statistical tools to measure variation among hosts in the fitness consequences of infection.”

Graham and her colleagues used the wealth of information collected over many years on the Soay sheep living on the island of Hirta, about 100 miles west of the Scottish mainland. These sheep provide a unique opportunity to study the effects of parasites, weather, vegetation changes and other factors on a population of wild animals. Brought to the island by people about 4,000 years ago, the sheep have run wild since the last permanent human inhabitants left Hirta in 1930. By keeping a detailed pedigree, the researchers of the St Kilda Soay Sheep Project can trace any individual’s ancestry back to the beginning of the project in 1985, and, conversely, can count the number of descendants left by each individual.

Expending energy to fight infection

Nematodes puncture an animal’s gut and can impede the absorption of nutrients. Therefore, tolerance to nematode infection could result from an ability to make up for the lost nutrition, or from the ability to repair damage the parasites cause to the gut, Graham said. “This island is way out in the North Atlantic, where the sun doesn’t shine much,” she said. “So tolerant individuals might be the ones who are better able to compete for food or better able to assimilate protein and other useful nutrients from the limited forage.”

Tolerant animals might invest energy in gut repair, but would then be expected to incur costs. Graham and her colleagues identified a similar evolutionary tradeoff in a 2010 study that compared immune-response levels and reproductive success in female Soay sheep. They found that animals with strong antibody responses produced fewer offspring each year, but also lived longer. The team has not yet been able to detect costs of parasite tolerance in the sheep, but such costs could help explain variation in tolerance if the most tolerant animals were at a disadvantage under particular conditions.

While the PLoS Biology findings provide strong evidence that natural selection favors infection tolerance, they do raise questions, such as how the tolerance is generated, and why variation might persist from one generation to the next despite the reproductive advantage of tolerance, Graham said. The data in this study did not permit the researchers to detect a genetic component to tolerance. If genetics do play a role, she suspects multiple genes may interact with environmental factors to determine tolerance; ongoing research will help to tease apart these possibilities.

Understanding the genetic underpinnings of nematode tolerance could someday guide efforts to boost tolerance in livestock by identifying and selectively breeding those animals that exhibit a heightened parasite tolerance, said David Schneider, an associate professor of microbiology and immunology at Stanford University.

“This study shows that parasite tolerance can have a profound effect on animal health and breeding success,” said Schneider, who is familiar with the work but was not involved in it. “In the long term, this suggests that it could be profitable to invest in breeding tolerant livestock.”

In humans and domesticated animals, intestinal parasites are becoming increasingly resistant to the drugs used to treat infections, Graham said. If the availability of nutrients, even just during the first few months of life, impacts lifelong parasite tolerance, simple nutritional supplements could be an effective way to promote tolerance in people. About 2 billion people are persistently infected with intestinal nematode parasites worldwide, mostly in developing nations. Children are especially vulnerable to the worms’ effects, which include anemia, stunted growth and cognitive difficulties.

“Ideally, we would clear the worms from the bellies of the kids who have those heavy burdens,” Graham said. “But if we could also understand how to ameliorate the health consequences and thus promote tolerance of nematodes, that could be a very powerful tool.”

Journal Reference:

  1. Adam D. Hayward, Daniel H. Nussey, Alastair J. Wilson, Camillo Berenos, Jill G. Pilkington, Kathryn A. Watt, Josephine M. Pemberton, Andrea L. Graham. Natural Selection on Individual Variation in Tolerance of Gastrointestinal Nematode Infection. PLoS Biology, 2014; 12 (7): e1001917 DOI:10.1371/journal.pbio.1001917

Bactéria pode aumentar inteligência (Exame)

Microbiologia | 24/05/2010 15:50

Cientistas acreditam que espécie também tem capacidades antidepressivas por aumentar níveis de serotonina no cérebro

Célio Yano 

São Paulo – Uma espécie de bactéria que os cientistas já acreditavam ter capacidades antidepressivas pode também deixar pessoas mais inteligentes. A descoberta foi apresentada hoje no 110º Encontro Geral da Sociedade Americana de Microbiologia (ASM, na sigla em inglês), realizado em San Diego, nos Estados Unidos.

“A Mycobacterium vaccae é uma bactéria de solo natural, que as pessoas geralmente ingerem ou respiram quando passam algum tempo na natureza”, disse Dorothy Matthews, que conduziu a pesquisa junto com Susan Jenks. Espécie não-patogênica, a M. vaccae tem esse nome por ter sido encontrada pela primeira vez em fezes de vaca.

De acordo com a ASM, estudos anteriores já haviam mostrado que bactérias da espécie mortas injetadas em ratos estimulam o crescimento de alguns neurônios que resultam no aumento de níveis de serotonina e reduzem a ansiedade.

Como a serotonina, tipo de neurotransmissor, desempenha um papel importante no aprendizado, Dorothy e Susan imaginaram que a M. vaccae vivas poderiam aumentar a capacidade de aprendizado do rato. Elas então alimentaram as cobaias com bactérias vivas e testaram a habilidade dos roedores para percorrer um labirinto. Conforme as pesquisadoras, os ratos que se alimentaram da bactéria atravessaram o labirinto duas vezes mais rápido e com menor índice de ansiedade que ratos que não haviam recebido o tratamento.

Em um segundo experimento, as bactérias foram removidas da dieta dos animais e eles foram testados novamente. Embora os ratos percorressem o labirinto mais lentamente do que haviam feito quando ingeriram a bactéria, eles ainda eram mais rápidos que os ratos que não haviam ingerido M. vaccae em nenhum momento. Após três semanas de descanso, os ratos ainda percorriam o labirinto mais rapidamente que os demais, mas os resultados já não eram mais estatisticamente significantes, o que sugere que o efeito foi temporário.

“Esta pesquisa mostra que M. vaccae pode ter uma função na ansiedade e aprendizado de mamíferos”, disse Dorothy. “É interessante imaginarmos que criar ambientes de aprendizado nas escolas que incluam momentos ao ar livre, onde M. vaccae esteja presente, pode baixar a ansiedade e aumentar a capacidade de aprender novas tarefas”, complementou.

Diet affects males’ and females’ gut microbes differently (Science Daily)

Date: July 29, 2014

Source: University of Texas at Austin

Summary: The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a new study. These results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

Illustration by Marianna Grenadier and Jenna Luecke. Credit: Image courtesy of University of Texas at Austin

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published this week in the journal Nature Communications. These results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

The researchers studied the gut microbes in two species of fish and in mice, and also conducted an in-depth analysis of data that other researchers collected on humans. They found that in fish and humans diet affected the microbiota of males and females differently. In some cases, different species of microbes would dominate, while in others, the diversity of bacteria would be higher in one sex than the other.

These results suggest that any therapies designed to improve human health through diet should take into account whether the patient is male or female.

Only in recent years has science begun to completely appreciate the importance of the human microbiome, which consists of all the bacteria that live in and on people’s bodies. There are hundreds or even thousands of species of microbes in the human digestive system alone, each varying in abundance.

Genetics and diet can affect the variety and number of these microbes in the human gut, which can in turn have a profound influence on human health. Obesity, diabetes, and inflammatory bowel disease have all been linked to low diversity of bacteria in the human gut.

One concept for treating such diseases is to manipulate the microbes within a person’s gut through diet. The idea is gaining in popularity because dietary changes would make for a relatively cheap and simple treatment.

Much has to be learned about which species, or combination of microbial species, is best for human health. In order to accomplish this, research has to illuminate how these microbes react to various combinations of diet, genetics and environment. Unfortunately, to date most such studies only examine one factor at a time and do not take into account how these variables interact.

“Our study asks not just how diet influences the microbiome, but it splits the hosts into males and females and asks, do males show the same diet effects as females?” said Daniel Bolnick, professor in The University of Texas at Austin’s College of Natural Sciences and lead author of the study.

While Bolnick’s results identify that there is a significant difference in the gut microbiota for males and females, the dietary data used in the analysis are organized in complex clusters of disparate factors and do not easily translate into specific diet tips, such as eating more vegetables or less meat.

“To guide people’s behavior, we need to know what microbes are desirable for people,” said Bolnick. “Diet and sex do interact to influence the microbes, but we don’t yet know what a desirable target for microbes is. Now we can go in with eyes open when we work on therapies for gut microbe problems, as many involve dietary changes. We can walk into those studies looking for something we weren’t aware of before. All along we treated diet as if it works the same for men and women. Now we’ll be approaching studies of therapies in a different way.”

Why men and women would react differently to changes in diet is unclear, but there are a couple of possibilities. The hormones associated with each sex could potentially influence gut microbes, favoring one strain over another. Also, the sexes often differ in how their immune systems function, which could affect which microbes live and die in the microbiome.

One notable exception in Bolnick’s results was in the mice. Although there was a tiny difference between male and female mice, for the most part the microbiota of each sex reacted to diet in the same manner. Because most dietary studies are conducted on mice, this result could have a huge effect on such research, and it raises questions about how well studies of gut microbes in lab mice can be generalized to other species, particularly humans.

“This means that most of the research that’s being done on lab mice — we need to treat that with kid gloves,” said Bolnick.

Bolnick’s co-authors are Lisa Snowberg (UT Austin); Philipp Hirsch (University of Basel and Uppsala University); Christian Lauber and Rob Knight (University of Colorado, Boulder); Elin Org, Brian Parks and Aldons Lusis (University of California, Los Angeles); J. Gregory Caporaso (Northern Arizona University and Argonne National Laboratory); and Richard Svanbäck (Uppsala University).

This research was funded by the Howard Hughes Medical Institute, the David and Lucile Packard Foundation and the Swedish Research Council.

Journal Reference:

  1. Daniel I. Bolnick, Lisa K. Snowberg, Philipp E. Hirsch, Christian L. Lauber, Elin Org, Brian Parks, Aldons J. Lusis, Rob Knight, J. Gregory Caporaso, Richard Svanbäck. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5500