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Tag: gut microbes

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Lately some articles have been mentioning the amazing possibility of new treatments for psychiatric disorders using bacteria as psychobiotics. Think of probiotics (microorganisms that have beneficial effects when consumed) that affect the brain. Researchers promoting the use of this term define a psychobiotic as "a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness". This new emerging field is just in its infancy. Lots of speculation and anecdotal evidence, and a few tantalizing studies.

I think the following article is a good introduction to this research area of the gut and mind/brain interaction, even though it was published in late 2013. Or you could order the newly published scholarly book "Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease" (Editors M.Lyte and J.F.Cryan) with a $189. purchase price (!).  From November 2103 NPR:

Gut Bacteria Might Guide The Workings Of Our Minds

Could the microbes that inhabit our guts help explain that old idea of "gut feelings?" There's growing evidence that gut bacteria really might influence our minds. 

"I'm always by profession a skeptic," says Dr. Emeran Mayer, a professor of medicine and psychiatry at the University of California, Los Angeles. "But I do believe that our gut microbes affect what goes on in our brains." Mayer thinks the bacteria in our digestive systems may help mold brain structure as we're growing up, and possibly influence our moods, behavior and feelings when we're adults. "It opens up a completely new way of looking at brain function and health and disease," he says.

So Mayer is working on just that, doing MRI scans to look at the brains of thousands of volunteers and then comparing brain structure to the types of bacteria in their guts. He thinks he already has the first clues of a connection, from an analysis of about 60 volunteers. Mayer found that the connections between brain regions differed depending on which species of bacteria dominated a person's gut. 

But other researchers have been trying to figure out a possible connection by looking at gut microbes in mice. There they've found changes in both brain chemistry and behavior. One experiment involved replacing the gut bacteria of anxious mice with bacteria from fearless mice. "The mice became less anxious, more gregarious," says Stephen Collins of McMaster University in Hamilton, Ontario, who led a team that conducted the research. It worked the other way around, too — bold mice became timid when they got the microbes of anxious ones. And aggressive mice calmed down when the scientists altered their microbes by changing their diet, feeding them probiotics or dosing them with antibiotics. 

Scientists also have been working on a really obvious question — how the gut microbes could talk to the brain. A big nerve known as the vagus nerve, which runs all the way from the brain to the abdomen, was a prime suspect. And when researchers in Ireland cut the vagus nerve in mice, they no longer saw the brain respond to changes in the gut. "The vagus nerve is the highway of communication between what's going on in the gut and what's going on in the brain," says John Cryan of the University College Cork in Ireland, who has collaborated with Collins.

Gut microbes may also communicate with the brain in other ways, scientists say, by modulating the immune system or by producing their own versions of neurotransmitters. "I'm actually seeing new neurochemicals that have not been described before being produced by certain bacteria," says Mark Lyte of the Texas Tech University Health Sciences Center in Abilene, who studies how microbes affect the endocrine system. "These bacteria are, in effect, mind-altering microorganisms."

This research raises the possibility that scientists could someday create drugs that mimic the signals being sent from the gut to the brain, or just give people the good bacteria — probiotics — to prevent or treat problems involving the brain. Experiments to test whether changing gut microbes in humans could affect the brain are only just beginning. 

One team of researchers in Baltimore is testing a probiotic to see if it can help prevent relapses of mania among patients suffering from bipolar disorder."The idea is that these probiotic treatments may alter what we call the microbiome and then may contribute to an improvement of psychiatric symptoms," says Faith Dickerson, director of psychology at the Sheppard Pratt Health System.

Mayer also has been studying the effects of probiotics on the brain in humans. Along with his colleague Kirsten Tillisch, Mayer gave healthy women yogurt containing a probiotic and then scanned their brains. He found subtle signs that the brain circuits involved in anxiety were less reactive, according to a paper published in the journal Gastroenterology.

But Mayer and others stress that a lot more work will be needed to know whether that probiotic — or any others — really could help people feel less anxious or help solve other problems involving the brain. He says, "We're really in the early stages."

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Two related studies showing the importance of the intestinal bacterial community for health and preventing diseases. Both also discuss how antibiotics disrupt the gut microbial community. From Science Daily:

Microbes help to battle infection: Gut microbes help develop immune cells, study finds

The human relationship with microbial life is complicated. Although there are types of bacteria that can make us sick, Caltech professor of biology and biological engineering Sarkis Mazmanian and his team are most interested in the thousands of other bacteria -- many already living inside our bodies -- that actually keep us healthy. Now, he and his team have found that these good bugs might also prepare the immune cells in our blood to fight infections from harmful bacteria.

In the recent study, published on March 12 in the journal Cell Host & Microbe, the researchers found that beneficial gut bacteria were necessary for the development of innate immune cells -- specialized types of white blood cells that serve as the body's first line of defense against invading pathogens.

In addition to circulating in the blood, reserve stores of immune cells are also kept in the spleen and in the bone marrow. When the researchers looked at the immune cell populations in these areas in so-called germ-free mice, born without gut bacteria, and in healthy mice with a normal population of microbes in the gut, they found that germ-free mice had fewer immune cells -- specifically macrophages, monocytes, and neutrophils -- than healthy mice. Germ-free mice also had fewer granulocyte and monocyte progenitor cells, stemlike cells that can eventually differentiate into a few types of mature immune cells. 

Khosravi and his colleagues next wanted to see if the reduction in immune cells in the blood would make the germ-free mice less able to fight off an infection by the harmful bacterium Listeria monocytogenes -- a well-studied human pathogen often used to study immune responses in mice. While the healthy mice were able to bounce back after being injected with Listeria, the infection was fatal to germ-free mice. When gut microbes that would normally be present were introduced into germ-free mice, the immune cell population increased and the mice were able to survive the Listeria infection.

The researchers also gave injections of Listeria to healthy mice after those mice were dosed with broad-spectrum antibiotics that killed off both harmful and beneficial bacteria. Interestingly, these mice also had trouble fighting the Listeria infection. "We didn't look at clinical data in this study, but we hypothesize that this might also happen in the clinic," says Mazmanian. "For example, when patients are put on antibiotics for something like hip surgery, are you damaging their gut microbe population and making them more susceptible to an infection that had nothing to do with their hip surgery?"

More importantly, the research also suggests that a healthy population of gut microbes can actually provide a preventative alternative to antibiotics, Khosravi says. 

From Science Daily:

Large study identifies exact gut bacteria involved in Crohn's disease

While the causes of Crohn's disease are not well understood, recent research indicates an important role for an abnormal immune response to the microbes that live in the gut. In the largest study of its kind, researchers have now identified specific bacteria that are abnormally increased or decreased when Crohn's disease develops. The findings, which appear in the March 12 issue of the Cell Press journal Cell Host & Microbe, suggest which microbial metabolites could be targeted to treat patients with this chronic and currently incurable inflammatory bowel disease.

Twenty-eight gastroenterology centers across North America have been working together to uncover how microbes contribute to the inflammatory cascade of Crohn's disease. Researchers took biopsies from 447 individuals with new-onset Crohn's disease and 221 nonaffected individuals at multiple locations along the gastrointestinal tract and then looked for differences between the two groups. They also validated their methods in additional individuals, resulting in a total of 1,742 samples from pediatric and adult patients with either new-onset or established disease.

The team found that microbial balance was disrupted in patients with Crohn's disease, with beneficial microbes missing and pathological ones flourishing. Having more of the disease-associated organisms correlated with increasing clinical disease activity. 

When the researchers analyzed the effects of antibiotics, which are sometimes used to treat Crohn's disease symptoms prior to diagnosis, they found that antibiotic usage in children with Crohn's disease could be counterproductive because it causes a loss of good microbes and an increase in pathological ones.

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Within the past few years there has been an explosion in human microbiome research - looking at the community of microorganisms that live in and on human beings. Within the body of a healthy adult, microbial cells are estimated to outnumber human cells ten to one! This community of microorganisms remains largely unstudied, and so their influence on human development, diseases, immunity, and health are almost entirely unknown.  Some of the latest research looks at the microbiomes of healthy people and those with diseases, seeing how they differ, and from that looking at possible treatments using bacteria.  This is a whole different mind-set from the one we've had for decades that viewed all bacteria as bad (pathogens) and needing to be eliminated. 

An introduction to this emerging area of human microbiome research was written by Gina Kolata in the NY Times, June 13, 2013:  

In Good Health? Thank Your 100 Trillion Bacteria

For years, bacteria have had a bad name. They are the cause of infections, of diseases. They are something to be scrubbed away, things to be avoided. But now researchers have taken a detailed look at another set of bacteria that may play even bigger roles in health and disease: the 100 trillion good bacteria that live in or on the human body.

No one really knew much about them. They are essential for human life, needed to digest food, to synthesize certain vitamins, to form a barricade against disease-causing bacteria. But what do they look like in healthy people, and how much do they vary from person to person?

In a new five-year federal endeavor, the Human Microbiome Project, which has been compared to the Human Genome Project, 200 scientists at 80 institutions sequenced the genetic material of bacteria taken from nearly 250 healthy people. They discovered more strains than they had ever imagined — as many as a thousand bacterial strains on each person. And each person’s collection of microbes, the microbiome, was different from the next person’s. To the scientists’ surprise, they also found genetic signatures of disease-causing bacteria lurking in everyone’s microbiome. But instead of making people ill, or even infectious, these disease-causing microbes simply live peacefully among their neighbors.

"Until recently, Dr. Bassler added, the bacteria in the microbiome were thought to be just “passive riders.” They were barely studied, microbiologists explained, because it was hard to know much about them. 

The work also helps establish criteria for a healthy microbiome, which can help in studies of how antibiotics perturb a person’s microbiome and how long it takes the microbiome to recover.

In recent years, as investigators began to probe the microbiome in small studies, they began to appreciate its importance. Not only do the bacteria help keep people healthy, but they also are thought to help explain why individuals react differently to various drugs and why some are susceptible to certain infectious diseases while others are impervious. When they go awry they are thought to contribute to chronic diseases and conditions like irritable bowel syndrome, asthma, even, possibly, obesity.

"The microbiome starts to grow at birth, said Lita Proctor, program director for the Human Microbiome Project. As babies pass through the birth canal, they pick up bacteria from the mother’s vaginal microbiome.

Babies born by Caesarean section, Dr. Proctor added, start out with different microbiomes, but it is not yet known whether their microbiomes remain different after they mature.In adults, the body carries two to five pounds of bacteria, even though these cells are minuscule — one-tenth to one-hundredth the size of a human cell. The gut, in particular, is stuffed with them.

“The gut is not jam-packed with food; it is jam-packed with microbes,” Dr. Proctor said. “Half of your stool is not leftover food. It is microbial biomass.” But bacteria multiply so quickly that they replenish their numbers as fast as they are excreted.

Including the microbiome as part of an individual is, some researchers said, a new way to look at human beings. The next step, he said, is to better understand how the microbiome affects health and disease and to try to improve health by deliberately altering the microbiome. But, Dr. Relman said, “we are scratching at the surface now.”

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FOR THOSE WHO WOULD LIKE TO SEE A VIDEO ON THIS TOPIC, this TED talk given by Dr. Jonathan Eisen  is an excellent introduction to the human microbiome and how we should view ourselves as being covered in a microbial cloud.  And that this microbial community within and on us should be viewed as an organ, and thus should be treated carefully and with respect.

Who are “Me, Myself and Us?”

2012Jonathan Eisen