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Gut health

Tuesday 20 July 2010

GutSociety member Peter has sent us links to three articles about gut health.

Peter said that "seeing as most of us seem to have an underlying gut issue like leaky gut or dysbiosis etc, I thought these were interesting."

From Scientific American:

What's in your gut?

By David Biello
Jul 14, 2010 07:45 PM

Modern science has revealed a startling fact that was first intimated by Anton von Leeuwenhoek scraping his teeth more than 400 years ago—you are more bacteria than you. Estimates put the number of microbial cells as constituting 10 times more of the cells in your body than actual human cells. What's worse, you better not get rid of them. Without them, you'll die.

This human microbiome, as scientists like to call it, has been the subject of much recent scrutiny, including a project to catalog the thousands or even millions of microbes within us and their function. After all, a better understanding of microbes and their role in our bodies could be the key to multiple health improvements and have led to new techniques, such as fecal transplants. Now a team of scientists led by microbiologist Jeffrey Gordon of Washington University in St. Louis has sequenced the "virome" or genetic code of "virus-like particles" from the poop of four pairs of female twins and their mothers, pulled from the Missouri Adolescent Female Twin Study that enlisted such women born between 1975 to 1986.

Perhaps unsurprisingly, female twins and their mothers tend to share the same set of such bacterial genetic material in their guts. After all, mothers inoculate infants with their gut bacteria during normal vaginal birth, and even C-section babies are almost instantly colonized by bacteria more commonly found on skin. But they don't share the same set of viruses—even though those viruses are living in roughly the same set of microbial cells. "Viromes are unique to individuals regardless of their degree of genetic relatedness," the researchers write in the July 15 issue of Nature. (Scientific American is part of the Nature Publishing Group.)

Droxidopa currently is not approved for use outside of Asia, but it's currently in clinical trials in the U.S., Canada, Europe and Australia. Some Phase III trials are now underway, meaning it could come on the market within the next couple of years.

Such diversity could help explain the different health outcomes observed in even the most genetically related people, such as twins. And the virome is a treasure trove of new genetic material—more than 81 percent of the viruses or virus-like particles were new to science. This inner voyage of tiny discovery (with outsized potential) is just getting underway.

The article oiginally appeared here.

From The New York Times:

How Microbes Defend and Define Us

Published: July 12, 2010

Dr. Alexander Khoruts had run out of options.

In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away, losing 60 pounds over the course of eight months. “She was just dwindling down the drain, and she probably would have died,” Dr. Khoruts said.

Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a piece of someone else’s intestines, or a stomach, or any other organ. Instead, he gave her some of her husband’s bacteria.

Dr. Khoruts mixed a small sample of her husband’s stool with saline solution and delivered it into her colon. Writing in the Journal of Clinical Gastroenterology last month, Dr. Khoruts and his colleagues reported that her diarrhea vanished in a day. Her Clostridium difficile infection disappeared as well and has not returned since.

The procedure — known as bacteriotherapy or fecal transplantation — had been carried out a few times over the past few decades. But Dr. Khoruts and his colleagues were able to do something previous doctors could not: they took a genetic survey of the bacteria in her intestines before and after the transplant.

Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria just didn’t exist in her,” said Dr. Khoruts. “She was colonized by all sorts of misfits.”

Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s microbes had taken over. “That community was able to function and cure her disease in a matter of days,” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and a co-author of the paper. “I didn’t expect it to work. The project blew me away.”

Scientists are regularly blown away by the complexity, power, and sheer number of microbes that live in our bodies. “We have over 10 times more microbes than human cells in our bodies,” said George Weinstock of Washington University in St. Louis. But the microbiome, as it’s known, remains mostly a mystery. “It’s as if we have these other organs, and yet these are parts of our bodies we know nothing about.”

Dr. Weinstock is part of an international effort to shed light on those puzzling organs. He and his colleagues are cataloging thousands of new microbe species by gathering their DNA sequences. Meanwhile, other scientists are running experiments to figure out what those microbes are actually doing. They’re finding that the microbiome does a lot to keep us in good health. Ultimately, researchers hope, they will learn enough about the microbiome to enlist it in the fight against diseases.

“In just the last year, it really went from a small cottage industry to the big time,” said David Relman of Stanford University.

The microbiome first came to light in the mid-1600s, when the Dutch lens-grinder Antonie van Leeuwenhoek scraped the scum off his teeth, placed it under a microscope and discovered that it contained swimming creatures. Later generations of microbiologists continued to study microbes from our bodies, but they could only study the ones that could survive in a laboratory. For many species, this exile meant death.

In recent years, scientists have started to survey the microbiome in a new way: by gathering DNA. They scrape the skin or take a cheek swab and pull out the genetic material. Getting the DNA is fairly easy. Sequencing and making sense of it is hard, however, because a single sample may yield millions of fragments of DNA from hundreds of different species.

A number of teams are working together to tackle this problem in a systematic way. Dr. Weinstock is part of the biggest of these initiatives, known as the Human Microbiome Project. The $150 million initiative was started in 2007 by the National Institutes of Health. The project team is gathering samples from 18 different sites on the bodies of 300 volunteers.

To make sense of the genes that they’re gathering, they are sequencing the entire genomes of some 900 species that have been cultivated in the lab. Before the project, scientists had only sequenced about 20 species in the microbiome. In May, the scientists published details on the first 178 genomes. They discovered 29,693 genes that are unlike any known genes. (The entire human genome contains only around 20,000 protein-coding genes.)

“This was quite surprising to us, because these are organisms that have been studied for a long time,” said Karen E. Nelson of the J. Craig Venter Institute in Rockville, Md.

The new surveys are helping scientists understand the many ecosystems our bodies offer microbes. In the mouth alone, Dr. Relman estimates, there are between 500 and 1,000 species. “It hasn’t reached a plateau yet: the more people you look at, the more species you get,” he said. The mouth in turn is divided up into smaller ecosystems, like the tongue, the gums, the teeth. Each tooth—and even each side of each tooth—has a different combination of species.

Scientists are even discovering ecosystems in our bodies where they weren’t supposed to exist. Lungs have traditionally been considered to be sterile because microbiologists have never been able to rear microbes from them. A team of scientists at Imperial College London recently went hunting for DNA instead. Analyzing lung samples from healthy volunteers, they discovered 128 species of bacteria. Every square centimeter of our lungs is home to 2,000 microbes.

Some microbes can only survive in one part of the body, while others are more cosmopolitan. And the species found in one person’s body may be missing from another’s. Out of the 500 to 1,000 species of microbes identified in people’s mouths, for example, only about 100 to 200 live in any one person’s mouth at any given moment. Only 13 percent of the species on two people’s hands are the same. Only 17 percent of the species living on one person’s left hand also live on the right one.

This variation means that the total number of genes in the human microbiome must be colossal. European and Chinese researchers recently catalogued all the microbial genes in stool samples they collected from 124 individuals. In March, they published a list of 3.3 million genes.

The variation in our microbiomes emerges the moment we are born.

“You have a sterile baby coming from a germ-free environment into the world,” said Maria Dominguez-Bello, a microbiologist at the University of Puerto Rico. Recently, she and her colleagues studied how sterile babies get colonized in a hospital in the Venezuelan city of Puerto Ayacucho. They took samples from the bodies of newborns within minutes of birth. They found that babies born vaginally were coated with microbes from their mothers’ birth canals. But babies born by Caesarean section were covered in microbes typically found on the skin of adults.

“Our bet was that the Caesarean section babies were sterile, but it’s like they’re magnets,” said Dr. Dominguez-Bello.

We continue to be colonized every day of our lives. “Surrounding us and infusing us is this cloud of microbes,” said Jeffrey Gordon of Washington University. We end up with different species, but those species generally carry out the same essential chemistry that we need to survive. One of those tasks is breaking down complex plant molecules. “We have a pathetic number of enzymes encoded in the human genome, whereas microbes have a large arsenal,” said Dr. Gordon.

In addition to helping us digest, the microbiome helps us in many other ways. The microbes in our nose, for example, make antibiotics that can kill the dangerous pathogens we sniff. Our bodies wait for signals from microbes in order to fully develop. When scientists rear mice without any germ in their bodies, the mice end up with stunted intestines.

In order to co-exist with our microbiome, our immune system has to be able to tolerate thousands of harmless species, while attacking pathogens. Scientists are finding that the microbiome itself guides the immune system to the proper balance.

One way the immune system fights pathogens is with inflammation. Too much inflammation can be harmful, so we have immune cells that produce inflammation-reducing signals. Last month, Sarkis Mazmanian and June L. Round at Caltech reported that mice reared without a microbiome can’t produce an inflammation-reducing molecule called IL-10.

The scientists then inoculated the mice with a single species of gut bacteria, known as Bacteroides fragilis. Once the bacteria began to breed in the guts of the mice, they produced a signal that was taken up by certain immune cells. In response to the signal, the cells developed the ability to produce IL-10.

Scientists are not just finding new links between the microbiome and our health. They’re also finding that many diseases are accompanied by dramatic changes in the makeup of our inner ecosystems. The Imperial College team that discovered microbes in the lungs, for example, also discovered that people with asthma have a different collection of microbes than healthy people. Obese people also have a different set of species in their guts than people of normal weight.

In some cases, new microbes may simply move into our bodies when disease alters the landscape. In other cases, however, the microbes may help give rise to the disease. Some surveys suggest that babies delivered by Caesarian section are more likely to get skin infections from multiply-resistant Staphylococcus aureus. It’s possible that they lack the defensive shield of microbes from their mother’s birth canal.

Caesarean sections have also been linked to an increase in asthma and allergies in children. So have the increased use of antibiotics in the United States and other developed countries. Children who live on farms — where they can get a healthy dose of microbes from the soil — are less prone to getting autoimmune disorders than children who grow up in cities.

Some scientists argue that these studies all point to the same conclusion: when children are deprived of their normal supply of microbes, their immune systems get a poor education. In some people, untutored immune cells become too eager to unleash a storm of inflammation. Instead of killing off invaders, they only damage the host’s own body.

A better understanding of the microbiome might give doctors a new way to fight some of these diseases. For more than a century, scientists have been investigating how to treat patients with beneficial bacteria. But probiotics, as they’re sometimes called, have only had limited success. The problem may lie in our ignorance of precisely how most microbes in our bodies affect our health.

Dr. Khoruts and his colleagues have carried out 15 more fecal transplants, 13 of which cured their patients. They’re now analyzing the microbiome of their patients to figure out precisely which species are wiping out the Clostridium difficile infections. Instead of a crude transplant, Dr. Khoruts hopes that eventually he can give his patients what he jokingly calls “God’s probiotic” — a pill containing microbes whose ability to fight infections has been scientifically validated.

Dr. Weinstock, however, warns that a deep understanding of the microbiome is a long way off.

“In terms of hard-boiled science, we’re falling short of the mark,” he said. A better picture of the microbiome will only emerge once scientists can use the genetic information Dr. Weinstock and his colleagues are gathering to run many more experiments.

“It’s just old-time science. There are no short-cuts around that,” he said.

The article originally appeared here.

And from Mark's Daily Apple:

Gut Flora and Your Healthy Immune System

By Mark Sisson
Apr 27, 2010

Last week, I discussed the importance of gut flora in the digestion of food while briefly touching on its role in early immunity, including the development of asthma and eczema – both of which are immune issues that appear to be exacerbated or caused by disrupted gut flora in children. But it goes much further than “just” asthma and eczema. Our gut flora plays a massive role in mediating our entire immune response. Think about this little factoid: the human gastro-intestinal tract houses the bulk of the human immune system, about 70% of it. And foreign gut flora actually aids and abets our innate immune response system by improving the function of our mucosal immune system and providing a physical barrier to invading microbiota. Before I get into that, though, let’s go over what we mean by immune system.

Some time back, I wrote a post discussing the three tiers of the human immune system:

  1. Anatomical barriers – Skin is the basic line of defense, along with mucus membranes and other physical responses like sweat, tears, and salivation, against the intrusion of foreign bodies and antigens.
  2. Innate/non-specific immune system – The innate immune system is the broad, generic response to bacteria and viruses that have made it past the anatomical barriers. Imagine bacteria entering through an open wound and the resultant inflammation, which is pretty much the body’s attempt at a catch-all response. Technically, the physical barriers are included in the innate system.
  3. Adaptive/specific immune system – The immune system can learn and improve its response to specific microbes over time and with repeated exposure; this is the adaptive immune system, and it’s only present in jawed vertebrates.

It’s generally accepted that gut flora affects and informs our immune systems, and how it does so, though a complicated, multi-faceted process, is beginning to be teased out by researchers.

Intestinal flora helps determine the quality of our mucosal immune system in several ways. First, it provides a physical barrier to colonization by foreign, deleterious microbes. As I mentioned earlier, infants receive the lion’s share of their gut flora from the mother (and surrounding environment) during birth and for the first year or so. This is a crucial time, because the first bacteria to gain a foothold are able to establish a long-lasting, mutually beneficial relationship with the host (that’s us). Good bacteria settles in and keeps bad bacteria out – for life (ideally, barring disruption of the population by poor diet and excessive antibiotic usage), which is why early intestinal colonization is so incredibly important for healthy function later in life. Though we’re talking tiny, invisible organisms, living quarters in the gut are still finite, and there are limits to how many microbes can be established. Compromised gut flora populations, for example, can allow harmful yeasts and bacteria to flourish. Healthy gut flora populations protect against invading microbes by simply taking up space and generally being more proficient at obtaining nutrients than the intruders. They’re playing defense, and informed, experienced defenders who know their way around always have the advantage.

Next, intestinal flora communicates with certain features of the immune system to help them focus on invading microbes. Ever wonder how our immune systems determine which bacteria to attack and which to ignore? After all, foreign microbes are foreign microbes, and immune cells aren’t “intelligent.” There’s got to be a mechanism behind it, some sort of “safe word” that causes immune cells to pass over the trillions of foreign bacteria residing in the gut. Good bacteria talks to the lymph nodes and provides a safe word, and the lymph nodes’ stromal cells produce “normal cell” antigens that tell the immune system not to attack the good bacteria. This conserves resources and improves the immune response by making it more efficient.

Intestinal flora can even influence the growth and formation of organs crucial to proper immune function. Take the thymus, for example, the primary function of which is to produce T-lymphocytes, also known as T-cells. T-cells are a type of white blood cell that has two functions. Killer T-cells destroy the body’s own cells that have been infected by viruses or bacteria; this prevents the offending microbe from replicating and causing more damage. Helper T-cells stimulate the production of antibodies. Both are vital, and both are made possible by the thymus. The thymus, in turn, is dependent on intestinal flora: formula-fed infants have smaller, less productive thymuses than breastfed infants. Okay, but how do we know that it’s the bacteria in breast milk making a difference? What’s one big thing that sets breast milk apart from formula? Beneficial bacteria, specifically Bifidobacteria, which is only present in breast milk. One recent study confirmed the effect of bacteria on thymus size when it compared thymus sizes in breastfed infants, standard formula-fed infants, and infants fed a fermented formula populated with Bifidobacteria. Infants given standard formula had smaller thymuses than infants in the other two groups; thymuses in infants given the fermented, bacteria-rich formula were similar in size and function to breastfed infants.

The study (PDF) of germ-free mice offers clear evidence that the presence of intestinal microbiota impacts the development of immune systems. Mice raised in isolation chambers, completely free of gut flora, exhibit a host of immunodeficiences: systemic lymphopenia, or low levels of lymphocytes, a kind of white blood cell extremely important to immune function; hypoplastic, or underdeveloped, lymphoid structures with compromised immune function; and poorly formed high endothelial venules, which are crucial pathways for the normal immune cell response. Colonization of germ-free mice with normal levels and species of gut flora, for the most part, normalizes immune function and structure.

90% of cells in the human body are microbial; a mere 10% are “human.” Perhaps it’s time we start redefining exactly what it means to be human. We couldn’t function without foreign gut flora. We’d be quivering and helpless, chronic hypochondriacs by necessity. Any variance in diet would probably immobilize us, and the mildest, gentlest pathogen would have its way with our tender bodies. It would be a bad scene all around.

Every organism – at least the larger, multi-cellular ones – has similar relationships with foreign microbes. The difference with humans is that we are consciously aware of their existence, and we devise methods to eliminate them from our bodies and our environment. Wild animals do not fret about such things; they live in ignorance of the teeming bacterial hordes handling the internal machinations. Oh, they may have protectionist instincts, like shying away from harmful or spoiled food, but they aren’t making the conscious decision to avoid bacteria. We have antibiotics, and soap, and surgical gloves, and gas masks. Our entire modern existence can perhaps be described as the avoidance of nature. Nature’s a scary place, with dark, dismal caves, dangerous predators, poisonous plants, and uncertainty, so we built walls, planted crops, tamed animals, and discovered fire. Humans are of “mother nature,” but we number in the billions only because we rejected and excluded her. And that’s the tricky part of being human, isn’t it?

Clearly, the best path for proper immunity is the early establishment of a healthy population of gut flora, ideally initiated immediately after birth. If you’re reading this, you’ve most likely been born, probably for quite some time now, but that doesn’t mean you should throw in the towel. On the contrary, we adults, more than anyone else, need to know the importance of gut flora. If we have children, it’s up to us to ensure they receive the proper exposure to beneficial bacteria. As for adults, the avoidance of sugar, vegetable oils, and lectin-rich grains and legumes to the inclusion of animal fatprotein, Primal starches, and leafy vegetables is a safe way to promote a healthy gut. Eating fermented foods and trying probiotic supplements may also help.

For anyone who’s still interested in this subject, I’d strongly advise you check out Dr. Art Ayer’s fantastic blog, Cooling Inflammation. Art suggests chronic, systemic inflammation stemming from disrupted gut flora as the root of most, if not all, diseases. He may be onto something here.

The article originally appeared here.



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