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I've heard that this has happened to a few people before in extenuating circumstances, but don't know where to search for more information on this. Is there a name for this? What are some major symptoms, and how does it affect the body? How is it identified?
This has never happened (at least to my knowledge), since removing all bacteria from a human being would be extremely difficult and also dangerous. And there is a proven relationship between the human microbiome and stress, but "extenuating circumstances" won't remove all bacteria from your body.
However you can look in the Internet for "germ-free animals", "gnotobiotic animal" or "axenic mice". Caesarean section in aseptic conditions is practiced (a fetus in normal conditions has no germs in it) and the "newborn" is immediately put in a sterilized enviroment. There is plenty of research with this kind of animals.
I hope my answer was useful for you! Cheers!
New study completes mapping of our gut bacteria
Scientist have mapped the genes of 500 previously unknown gut bacteria and more than 800 bacteriophages. This means that all intestinal bacteria are now mapped.
The total amount of genes in the gut flora is more than 100 times that of our own genome and most of those bacteria play an important role for health.
Many of the bacteria are essential for our immune system. Furthermore, recent research has shown how gut flora can influence the development of diseases and disorders such as ADHD, diabetes, and obesity.
The gene map can be used to strengthen our understanding of a long list of disorders and in the search for new types of antibiotics, says Associate Professor Henrik Bjørn Nielsen, who helped conduct the study at the Centre for Systems Biology at the Technical University of Denmark.
Treatment using bacteriophages is already used today, among other places in Russia and Georgia.
The method was was already developed in the 1920s but never caught on outside the Soviet Union. The main reason being that the rest of the world decided to focus on antibiotics instead, for example penicillin.
As more and more bacteria are becoming resistant to antibiotics, scientists are now considering phage therapy as a possible form of treatment.
&ldquoGut bacteria has been one of the hottest scientific topics in the past four years. Prior to our study, only around 10 percent of these bacteria were known. We have mapped the remaining 90 percent. This could lead to major medical progress in the future,&rdquo says Nielsen.
Allan Flyvbjerg, Dean of Health at Aarhus University, did not participate in the new study but is very excited about the results.
"Gut bacteria is a thrilling area of research. We have between 1.5 and 2 kilos of bacteria in our guts and all indications point to the fact that these are directly linked to our health and illnesses. This study provides an accurate picture of the kind of bacteria which live in the gut,&rdquo he says.
The study was recently published in Nature Biotechnology.
The discovery holds great potential
The possibilities created by the newly mapped bacterial genomes are huge.
By using the genomes, scientists could find out which bacteria are either present or missing in the gut of people with diseases such as type 2 diabetes, chronic, inflammatory bowel diseases, autism, ADHD, and schizophrenia -- or people who are severely obese.
New therapeutic treatments could become possible where bacteria are either removed or added to the gut in order to change the total gut flora and thereby creating a more healthy system.
"It&rsquos already proven that you can take gut bacteria from a fat mouse and transfer it to a thin mouse. And then the thin mouse becomes fat," says Nielsen.
Flyvbjerg agrees that the study could pave the way for treating a variety of diseases through manipulation of the gut flora.
&ldquoIn order to manipulate the gut flora as a means of treatment we needed to dig a little deeper into the understanding of the bacteria that live there. This, I feel we have come closer to understanding now,&rdquo he says.
Bacteria influences the absorption of medicine
The discovery could also be used to better understand how drugs are absorbed through the gut. When medication is orally consumed the gut bacteria is the first to encounter and digest the medicine.
This means that medicine is digested very differently from person to person depending on the bacterial composition in their gut.
We can now start to explore solutions for this, explains Nielsen:
"We can begin to understand the interaction between bacteria and us in a more nuanced way. Since each of us seem to have different bacterial combinations in the gut we can start to consider whether we should also have varying amounts and types of medication to achieve the same desired goals or to avoid certain side effects,&rdquo he says.
Bacterial-virus could become a new antibiotic
The study also points to a new way of understanding antibiotics.
In the study, the scientists not only mapped different bacterial genomes. They have also mapped bacteriophages&rsquo (viruses that infect bacteria) genomes.
In the process they discovered 800 new bacteriophages.
The scientists looked at which and how bacteriophages attack and destroy particular bacteria.
The experiment involved observing bacteria and bacteriophages activity over time. Specific bacteria and specific bacteriophages were placed together in a sample and the scientists could then watch how the bacteria disappeared over time.
By doing so it was possible to conclude which bacteriophages finish off which bacteria.
This type of antibiotics, known as phage therapy, could very well have a central role within future treatment.
"By using bacteriophages we&rsquore focusing treatment, aiming directly towards one type of bacteria rather than shooting around aimlessly as one does today with antibiotics,&rdquo says Nielsen. &ldquoIt&rsquos much healthier for the gut flora and therefore also the body. Also, we get a new type of antibiotic with a lot of potential -- since bacteriophages are constantly evolving alongside bacteria, the therapy can be updated continuously as the bacteria become resistant.&rdquo
Like collecting thousands of puzzles
In order to discover the 500 remaining genomes, it was necessary for the scientists to smash up the total amount of DNA mass within the gut flora into millions of bits. This created a gigantic hotchpotch of DNA fragments which the scientists then needed to sort out. It corresponds to having to assemble thousands of puzzles, each with tens of thousands of pieces that are all mixed together in one big pile.
In this imagery the number of puzzle pieces translate to the genes in the bacterial genomes. However, unlike a puzzle, the genes do not only fit one puzzle but also many other games.
The scientists hypothesized that genes which originate from the same bacterial species, should exist in the same amounts -- e.g. if there&rsquos 1,000 copies of one gene and 1,000 of a second gene then the different parts may originate from the same kind of bacteria.
The scientists retrieved intestinal bacteria from 400 Europeans. This meant they could observe whether or not the ratio between different parts showed the same pattern no matter the individuals&rsquo particular compositions of intestinal bacteria.
In this way the scientists pieced together the bacteria bit by bit until they had collected the genomes of 741 bacteria -- of which approximately 250 were already known.
"We did not use any prior knowledge about known bacteria and bacteriophages in our analysis. We have simply shown how much information there was in the data [from the DNA]. It's beautiful science -- even if it is a little geeky,&rdquo says Nielsen.
Introduction to the virome
With an estimated population of 10 31 , viruses are the most numerous biological entities on Earth, inhabiting diverse environments ranging from the oceans to hydrothermal vents to the human body . The human body is inhabited by both prokaryotic (mostly bacterial) and eukaryotic (mostly human) viruses. Researchers have historically focused on eukaryotic viruses because of their well-known impact on human health, including the influenza virus that causes seasonal flu epidemics and the viruses that cause devastating health consequences like HIV and Ebola. However, increasing evidence suggests that prokaryotic viruses can also impact human health by affecting the structure and function of the bacterial communities that symbiotically interact with humans [2, 3]. The viruses that infect bacteria, called bacteriophages, can play a key role in shaping community structure and function in ecosystems with high bacterial abundance [4, 5] such as the human gut.
In recent years viruses have gained their own “-ome” and “-omics”: the virome and (meta)viromics. These terms encompass all viruses inhabiting an ecosystem along with their genomes and the study of them, respectively. These viruses can be classified in many ways including on the basis of their host (Fig. 1). In this review we focus on bacteriophages, mainly in the human gut ecosystem, and discuss their role in human health. We then lay out the challenges associated with the study of the gut virome, the existing solutions to these challenges, and the lessons that can be learned from other ecosystems.
Viruses can be classified based on various characteristics. These terms are used continuously throughout this manuscript. While all characters are important in determining taxonomic relationships, sequence comparisons using both pairwise sequence similarity and phylogenetic relationships have become one of the primary sets of characters used to define and distinguish virus taxa 
Gut microbial diversity and digestive function of an omnivorous shark
The intestinal microbiome of vertebrates has been shown to play a crucial role in their digestive capabilities. This is particularly true for omnivores and herbivores that rely on enteric microbes to digest components of plant material that are indigestible by host-derived enzymes. While studies of microbe-host interactions are becoming more frequent in terrestrial systems, studies of this type are still limited in marine systems, particularly for higher trophic level organisms. Although sharks are largely carnivorous, the bonnethead shark (Sphyrna tiburo) has been identified as an omnivore, given that it assimilates seagrass material in addition to proteinaceous prey items such as crustaceans. The mechanisms by which bonnetheads digest seagrass, including microbial digestion, are still unknown. We use digestive enzyme assays, histological imaging, measurements of microbial fermentation, and 16S rDNA sequencing to explore potential processes by which the bonnethead shark may digest and assimilate plant material. We found evidence of microbial fermentation (as evident by moderate short-chain-fatty-acid concentrations) as well as evidence of greater epithelial surface area in their spiral intestine compared to other gut regions. We identified specific orders of microbes that make up the majority of the bonnethead shark gut microbiome (Vibrionales, Clostridiales, Pseudomonadales, Mycoplasmatales, Rhizobiales, and others), some of which are known, in other organisms, to be involved in the production of enzymes responsible for the breakdown of chitin (found in crustacean shells) and components of cellulose (found in seagrass). Our results highlight that an organism from a stereotypical “carnivorous” group is capable of breaking down seagrass, including potential for some fiber degradation, as well as advances our knowledge of gut microbe community structure in sharks.
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The gastrointestinal tract is routinely defined as "a tube approximately 19-22 feet long, running through the body from mouth to anus." The World Book Dictionary adds that the intestine is "the lower part of the alimentary canal" food from the stomach passes into the intestine for further digestion and for absorption."
This boringly simplistic concept of intestinal function, combined with its indisputable lack of glamour, is reason enough for most people to never give the importance of intestinal health a second thought. This is unfortunate, possibly even dangerous, and needs to change. The reality is that healthy intestinal function is critically important to overall health. This realization makes it incumbent upon all those desiring good health to understand the importance of optimal intestinal health and adjust their habits into alignment with that knowledge.
The Intestine as a Protective Barrier
Consider as an analogy the atmosphere surrounding the earth and its role in protecting our environment. It parallels the function of the intestine and its role in protecting our overall health. The earth's atmosphere provides a protective barrier to support and sustain the abundant variety of life found here. It is important to note that balance is the key! The atmosphere is composed of a critical balance of different gases that enable it to provide the earth with important filter-like protection. Selectively screening out anything that could be damaging to, or allowing the penetration of anything that would be necessary for, 30 million different species of inhabitants.
In principal, the intestine provides a very similar protective barrier. The healthy intestinal wall is coated with hundreds of different species of microorganisms, both healthful and unhealthful bacteria numbering in the billions. This rich, protective coating of micro-organisms acts in concert with the physical barrier provided by the cell lining the intestinal tract with factors, to provide the body with important filter-like protection. Damaging substances like unhealthy bacteria, toxins, chemicals and wastes are filtered out and eliminated. Simultaneously, the critical factors needed for fife, such as nutrients and water, are absorbed into circulation and made available to the billions of cells in the body that need them.
The atmosphere acts as a selective barrier making sunlight available for fife-sustaining photosynthesis, while simultaneously preventing the sun's disease-causing ultraviolet light from penetrating. Damaging ultra-violet radiation is screened out by a protective portion of the atmosphere called the ozone layer. The selective barrier function of the intestine is equally profound.
In the healthy state, the absorption of small sugars, fats and proteins proceed through the intestinal wall and circulate throughout the body. They are required for a myriad of essential reactions. Simultaneously, damaging substances from unhealthful bacteria, incompletely digested food, toxins, or chemicals, are largely prevented from being absorbed and transported throughout the body. We are continually and unknowingly protected from the ill effects of these damaging substances.
Bad Habits That Negatively Impact Intestinal Health
Unfortunately human beings have developed bad habits that promote imbalance in both the atmosphere and the intestinal tract.
For example, pollutants such as chloro-fluoro-carbons (CFCs) have punctured holes in our ozone shield. The ozone hole has widened and deepened every year since scientists began measuring ozone levels in 1985. Scientists feel that the continued depletion of the ozone layer will cause greater amounts of ultraviolet radiation to reach earth, resulting in greater cancer risk, as well as other health problems.
Our societies bad habits in general have contributed to an imbalance of intestinal protective factors in an alarming percentage of the population. These bad habits include wide spread consumption of a diet high in refined, simple sugars and fat and deficient in nutritious, whole, unprocessed foods and fiber. This type of diet could potentially tip the intestinal balance toward the overgrowth of unhealthful bacteria and the proliferation of yeast or fungal organisms. It is also associated with less frequent bowel movements and a number of forms of chronic intestinal dysfunction. Other bad habits include the excess consumption of alcohol and the use of DETOXIFICATION.
The Growing Problem of Toxicity
In recent history mankind has managed to drastically change the bio-chemistry of our environment in which we live through a process of ever increasing pollution. For example, in 1989 alone:
1. More than 1,000,000,000 pounds of chemicals were released into the ground, threatening a portion of the soil we grow our food in and the natural underground water tables that supply some of our drinking water.
2. Over 188,000,000 pounds of chemicals were discharged into surface waters such as lakes and rivers.
3. More than 2,400,000,000 pounds of chemical emissions were pumped into the air we breathe.
4. A grand total of 5,705,670,380 pounds of chemical pollutants were released into the environment we eat, breathe and five in, all in just one year.
To compound the problem of our toxic environment, we have refined away much of the nutritional value of our food supply and replaced it with artificial colorings, preservatives, flavorings, conditioners, etc. This poor quality diet-combined with extensive use of antibiotics in medicine and agriculture-may have predisposed many of us to experience a kind of "internal" pollution. Internal pollution occurs when the healthful bacteria in the intestinal tract are overcome by unhealthful bacteria. These unhealthful bacteria release toxic by-products into our circulation that can negatively impact many aspects of our overall health.
Will Toxicity Have An Effect on You?
What does this problem of toxicity mean for us individuals? It may present a threat to the vibrant level of health we would like to enjoy. We succumb to the adverse effects of toxicity depends on our knowledge of the subject and the choices we make.
We need to take personal responsibility to make sure that we do not fall victim to toxicity. That involves learning what we need to do to help our body protect itself from toxicity.
Basic Ways to Avoid Toxicity
Let's been with some of the basic requirements to avoid toxicity. Do all you can to purify your work and home environments. If you know the source of any toxic materials at work, such as stored or leaking chemicals, dyes, paints, solvents, glues, acids, or household offenders such as insecticides or cleaning agents, remove them if possible. If the offending materials cannot be removed, an effective air purification system may be needed. At least, wear protective clothing and/or breathing apparatus when using any toxic materials. Regular replacement of furnace and air conditioning filters may also be helpful.
It is also very important to eat a good diet with plenty of fresh, wholesome foods. Avoid eating excess fat, refined sugar and foods high in additives and preservatives. Eat moderate levels of protein (approximately 15% to 20% of your calories) and fat (approximately 20% of your calories), while increasing levels of complex carbohydrates (approximately 60% of your calories). Substitute organically raised animals and organically grown fruits and vegetables whenever possible. Drink plenty of purified water (ideally, eight 8-ounce glasses a day). A home water purification system is highly desirable to provide pure water for drinking and cooking.
Support Your Body's Efforts to Eliminate Toxicity
One thing is certain in our effort to purify our work and home environments it is impossible to avoid toxicity completely! With that realization, the importance of supporting your body's efforts to eliminate accumulated toxins cannot be overstated.
Water or Juice Fasts Less Complete
It was believed that a water or juice fast was preferred detoxification thought to work under the principle that the body will be able to clear stored toxins and heal itself when the "stress" of digestion and the further accumulation of toxins were eliminated.
The modern-day realization that the body's detoxification mechanism is a heavily nutrient-supported process has made it clear that simple juice or water fasting is less complete and no longer the method of choice. Prolonged fasting may weaken muscles and various organs because of protein losses and a gradual slowing of metabolic activity as the body endeavors to conserve its depleted energy resources.
More Complete Support for Detoxification
A more current approach to detoxification is to nourish the body thoroughly, fueling its natural detoxification mechanism with the nutrients needed to achieve optimal detoxification activity. By providing high-quality protein, complex carbohydrates and essential fats, the body gets what it needs to prevent muscle and organ breakdown and depleted energy resources. This is just the beginning in order to improve our health. Nutrients are needed to support the function of the organs directly involved in detoxification: the liver, the intestinal tract and the kidneys. Intelligent Application of nutrition may help in the following ways:
Intestine: The nutrient's zinc and pantothenic acid, the amino acid L--glutamine are necessary for optimal health. Carbohydrates known as fructo-oligo-saccharides, and microorganisms known as acidophilus and bifidus, are a few of the substances that provide support for the health and integrity of intestinal function. In a proper state of health, the intestine promotes elimination of toxins through:
1. regular daily bowel movements
2. eliminating the build-up of unhealthful microorganisms and internal toxins
3. providing a strong and intact barrier to prevent the leaking of toxic materials from the intestines into circulation.
Liver: The vitamins A, B3, B6, C, E, beta-carotene, the amino acids L-cysteine and L-glutamine, and components known as glutathione and phosphohpids are some of the substances that support liver function. In a proper state of function, the liver filters out and transforms toxic substances that have entered the blood into harmless substances that can be excreted in the urine. Interestingly it appears that the ratio of dietary protein to carbohydrate may be a very important factor in determining the ability of the body to detoxify certain substances.
Kidney: The vitamins A, C, B6, and the mineral's magnesium and potassium, are just some of the substances that support kidney activity. The kidney provides a major route of toxin excretion via the urine. Fat: Weight reduction and management are helpful for those who are overweight. Excess fat provides a ready storage site for fat-loving toxins entering the body. Once deposited there, it is very difficult to remove them. Unless the excess fat is removed, they remain there with the possibility of being a continual source of toxicity.
Find the Help You Need
If you have any questions as to what you can do to help eliminate internal pollution and how to improve intestinal health, do not hesitate to ask us. Antacids and non-steroidal anti-inflammatory pain relievers are a major contributor to poor health of the gastro-intestinal tract. These may contribute to a breakdown or deterioration in the physical integrity of the intestinal wall, much as if CFCs have punctured the ozone layer, creating holes for ultraviolet radiation to enter through.
Scientists describe this state of intestinal breakdown as "leaky gut syndrome" and feel it may contribute to intestinal dysfunction.
A high stress lifestyle combined with a bad diet, deficient in important nutrients such as L-glutamine, pantothenic acid, zinc, folic acid, vitamin B12, vitamin A and others, may impair the healing of intestinal deterioration. Read our article to learn how your diet can support gut health: Foods to Heal Leaky Gut & Foods to Avoid.
Another bad habit is the over use of broad spectrum antibiotics. Researchers have acknowledged that virtually every antibiotic taken orally causes' alterations in the balance of the bacteria in the intestine. Even as little as one course of antibiotics may deteriorate that rich, protective coating of microorganisms and upset the balance between healthful and unhealthful bacteria, reducing the resistance to intestinal and systemic ill health.
Helpful Suggestions for Achieving Optimal Intestinal Health
Those interested in how to improve their intestinal health should find the following suggestions helpful:
1. Avoid excessive alcohol use and refined, sugar rich, fiber-poor foods.
2. Avoid the use of antacids and broad spectrum antibiotics as much as is possible.
3. Eat a diet rich in whole, unprocessed, nutritionally adequate foods and fiber.
4. Drink plenty of pure water.
5. Consume a diet rich in fiber, supplement the diet with pro-biotic proteins (lacto-peroxidase, lacto-ferrin) and globulin proteins that may support a balanced and healthful population of intestinal bacteria.
6. Also consider adding to the diet fructo-oligo-saccharides (FOS) which act as a food source to nourish certain healthful bacteria but not unhealthful ones.
7. Finally, supplement the diet with scientifically proven, high quality, healthful bacterial products such as bifido- bacteria and the NCFM strain of Lactobacillus acidophilus.
Author: Mark Occhipinti, M.S., Ph.D., ND
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Do Your Gut Bacteria Influence Your Metabolism?
In a new study, researchers were able to make mice lean or obese by altering their gut bacteria. Jeffrey Gordon, an author of the study, discusses how the interaction between diet and the microbial community in our gut influences our health.
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Down The Gullet: A Guided Tour Of Your Guts
This is SCIENCE FRIDAY. I am Ira Flatow. Did you know that trillions of bacteria live in your gut, happily dining on the food you eat? And your bacteria community, well, it's different than mine everyone has a different community and that is important because as a new study published in Science points out, the specific bacteria you shelter can alter your metabolism. It can help determine your health. How do you get the bacteria in your gut? What connection do they have to our well-being?
Jeffrey Gordon is a microbiologist and director of the Center of Genome Science and Systems Biology at the Washington University School of Medicine in St. Louis. He's also an author on that paper and he joins us from the studio at Washington University. Welcome to SCIENCE FRIDAY.
JEFFREY GORDON: Pleasure to be able to talk with you.
FLATOW: Thank you. Let's talk about the gut bacteria. You looked at gut bacteria and how it could transmit lean or obese traits. Tell us how you tested that.
GORDON: Well, we started out with twins, where one twin was obese and the other twin was lean. There's been a lot of work trying to understand how these trillions of organisms relate to our health status. So we did a test. We ask how much of the obese twin's weight and metabolism could be ascribed to their bacteria and we transplanted these bacterial communities into sterile mice.
We did the same thing for the lean twin and waited. Then we saw that the mice that had received the obese donor's gut community increased the amount of fat in their body, gained more weight and had some of the metabolic features associated with human obesity.
FLATOW: Wow. Could you reverse that?
GORDON: Well, that's a good question. So we tried to actually prevent this. We took the same approach, but soon after we transplanted the communities, we co-housed, put in the same cage, a mouse that had received the obese twin's community and a mouse that had received the lean twin's community. That's what we call the battle of the micro biota. And the presence - the presence of - it sounds very dramatic and the results were actually quite dramatic.
The obese community was transformed so that the mouse that harbored it began to acquire the features of the lean community. There was an invasion of microbes from the lean community in one of the mice into the community that harbored the obese community. That transformation prevented the development of increased body weight and fat content and eliminated the metabolic features associated with obesity.
FLATOW: So somehow then the micro biota, the bacteria were controlling metabolism?
GORDON: That's right. First of all, the remarkable things was that the invasion was one way. The lean bugs went into the obese community, transforming it, but not vice versa. And you're absolutely right. There were job vacancies in the obese community, openings that were filled by these organisms from a lean gut community.
FLATOW: And do we know the mechanism by how the metabolism was changed?
GORDON: Well, we know what functions certain groups of bacteria are responsible for because we actually took notice of who were the invaders. And it was that process of invasion by these groups of organisms that collectively are called the bacteroidedes(ph) that were associated with this prevention of the increased weight and metabolism.
We knew who the actors were, but we also asked the question, why isn't there an epidemic of leanness if these things can occur, at least in this setting.
GORDON: Well, it's diet, diet, diet. The first battle of the micro biota was done with mice eating a standard mouse chow. Low in fat and high in plant fiber. So we tried to make the battle more realistic. Not only did we transplant human gut microbes into the recipient mice, but we also gave them human diets. Two different types of diets based on the types of diets we consume in America.
One diet representing a diet that was consumed by people who favored low fats and high fruits and vegetables in their daily menus, and just the opposite type of diet - high saturated fats, low in fruits and vegetables. So with the healthier diet, the invasion occurred, there was a prevention of the weight gain and the metabolic features I described, but that invasion and that prevention was not evident when the mice were consuming the high saturated fat diet.
So it's evident to us that these job vacancies can't be fulfilled unless the right diet is being consumed.
FLATOW: Is that because the bacteria prefer a high fiber diet like that to survive and so they'll populate more?
GORDON: That's the general idea. There are ingredients in the diet that the bacteria can utilize, can process in ways that help themselves as well as help us, and the diet and microbes collude, collaborate, the shape, the properties of these communities, and affect us.
FLATOW: What about other things? Since it's controlling metabolism, what about other things that are going on in the body? Are they influenced also?
GORDON: Yes. And I think you're alluding to the fact that obesity is a very complex puzzle with lots of parts - how much food we consume, how much exercise we do each day. The question was, could our microbial communities, which are tasked with the responsibility of transforming the foods that we eat into metabolic products that shape our biology and our biological differences, what role do they play?
FLATOW: Yeah. Well, if you know what bacteria makes you lean and you know how to feed them the right food, why can't we all start that diet and find a probiotic that would work that way and lose weight and get healthier?
GORDON: Well, let me answer that question in a couple of ways. By probiotic you're referring to a different type of probiotic, not the type of probiotics that are present in fermented milk products that everybody is most familiar with. But we're talking about organisms that are naturally occurring, that have adapted to life in our gut, that haven't been genetically modified. We're looking for those creatures that we want to give.
And yes, we have to figure out which one of these groups of bacteria are most helpful in different populations of people. That's one test. And then to match the diet with their capacity. So we can't think of food in a way that's divorced from the microbes that live in our guts.
FLATOW: So it's not as easy as hanging out with leaner people and you might get some of their bacteria that you might like to make you lean? Could it be that easy?
GORDON: Well, it would be useful to look at the lifestyles of lean individuals, but at the same time, yes, it's not easy, but there is hope. And I think that these types of experiments point to another facet of our biology that we might be able to manipulate intentionally in ways that could enforce health and perhaps at very early stages of our lives.
FLATOW: So there is an environmental influence outside the body and something that's in your family perhaps that could be affecting the bacteria.
GORDON: Well, we also know that obesity is associated with a less diverse microbial community. That goes back to this concept of job vacancies. Are there vital functions that aren't represented in the microbiota of an obese individual.
GORDON: So the answer is yes.
FLATOW: Yeah, so I remember reading research about that, that the more diverse your bacteria are, the better it is.
GORDON: That's exactly right. And of course, what kind of foods should we create to help cultivate this microbial garden?
FLATOW: You know, this is what foodies like Michael Pollan and people have been saying now for a long time, that if you get, you know, these complex foods that you eat, they're going to be feeding those gut bacteria.
GORDON: Exactly. And we can't think of the value of foods independently of the microbes that we harbor. And we have to think of the consumer's microbial communities. I think that offers a great deal of opportunity to design foods from the inside out, not just from the outside in.
FLATOW: So what's your next step here?
GORDON: A couple of things. Number one, to see which microbes function as invaders but where the donors of these communities represent different ages, different cultural traditions, different lifestyles. To really hone in on whether there's a set group of microbes that can fulfill functions of the type we elude to or whether we're going to have to customize these groups of microbes. That's step one.
The other step is to see what we can do with our existing diets to remove or add ingredients that may support the important health-promoting activities that these microbes we talk about.
FLATOW: You know, it almost seems like this whole field of the microbiota, the bacteria in your gut is just now just — use a bad phrase - exploding. You know, the research in the news that's coming out as if we discovered something new.
GORDON: And of course it's as old as microbiology and as old as us. I think that the ability to describe differences between microbial communities and healthy and diseased populations is one important step. And that's been very stimulating and very enticing. The challenge, as illustrated by this study, is to actually set up systems to test whether these differences are cause or effect. And here we have evidence for cause, and that's helpful.
FLATOW: So should - how transferable is this stuff from mice to people yet?
GORDON: Well, that's an excellent question. Of course the mice are designed to incorporate the features of the very human population that we want to help. So it's that population's microbes that are installed into the guts of these sterile mice. And it's their diets. So we try to anticipate how to translate this information to the very humans that supply the microbes and the foods that help us construct these models.
FLATOW: So we're just beginning down that road to figure this out. Yeah, all right. Well, thank you very much, Dr. Gordon. This is quite fascinating and it's something we can all relate to.
FLATOW: Go for those — so the take-home message is go for that high fiber, high fiber diet to feed the biome there.
GORDON: And you never dine alone.
FLATOW: You're not eating, you're not eating for one. Your turn. All right. Dr. Jeffrey Gordon is a microbiologist and director of the Center of Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis. We're going to take a break and when we come back we're going to talk lots more about, well, a search for life on earth by looking at Mars. Could we all be Martians in origin? Interesting stuff coming up after the break, so stay with us.
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Bacterial pathogens and host metabolism
Anorexia, malaise and diarrhea are all symptoms of intestinal infection. In the developing world, multiple intestinal infections in rapid succession are an important cause of malnutrition, wasting and a general failure to thrive in children under five (Kotloff et al., 2013). Although the rapid transit of nutrients through the intestine that defines diarrhea is bound to be responsible for some of this, research in Drosophila has elegantly revealed pathogen impacts on host metabolism that extend beyond decreased intestinal transit time.
Mycobacterium marinum, a mycobacterial species that causes skin infections associated with abrasions acquired during water exposure, is sometimes used as a model for Mycobacterium tuberculosis (Deng et al., 2011). Early work by the Schneider laboratory showed that, when injected into the Drosophila hemolymph, this extra-intestinal pathogen caused wasting through dysregulation of insulin signaling (Dionne et al., 2006). The ultimate result was a decrease in glycogen and triglyceride stores along with an elevation in systemic glucose levels, suggesting that systemic infections might cause insulin resistance in Drosophila as they do in mammals (Gheorghita et al., 2015). The study by Dionne et al. set the stage for subsequent explorations of the impact of diarrheal pathogens on Drosophila metabolism.
It has been shown using flies that systemic infection with the intestinal pathogens Salmonella typhimurium and Listeria monocytogenes, but not the common intestinal inhabitant Enterococcus faecalis, results in anorexia (Ayres and Schneider, 2009). Development of anorexia, in turn, impacts expression of antimicrobial peptides and susceptibility to infection. Thus, the host metabolic state can alter interactions with invading pathogens by modulating the innate immune response. Interestingly, this group also reported that anorexia was induced by decreased expression of the gustatory receptor Gr28b (Ayres and Schneider, 2009), which is highly expressed in enteroendocrine cells (Buchon et al., 2013 Marianes and Spradling, 2013). This gustatory receptor, as well as others expressed on the surface of intestinal cells, provides a mechanism whereby the products of pathogenic intestinal microbes can activate signaling pathways that alter host satiety and susceptibility to infection.
The group led by David Schneider subsequently employed metabolomic studies to demonstrate that L. monocytogenes infection decreased glycogen and triglyceride stores as well as the glucose concentration in the hemolymph (Chambers et al., 2012). The group also noted that levels of the anti-oxidant uric acid were decreased. Although these changes are presumably the result of infection-induced anorexia and other bacterial impacts on the host, this study did not conclusively identify these changes in host metabolism as components of a pathogen virulence program, a host innate immune response or a specific host–pathogen interaction pathway.
Because of the speed and affordability of genetics, the comprehensive mutant and transgenic RNA interference (RNAi) lines, and the eminently accessible and extensive databases, the Drosophila model is ideally suited to rapid dissection of host–pathogen interactions (Ni et al., 2008,, 2011 Cook et al., 2010 dos Santos et al., 2015). Using these tools, subsequent studies have thus far revealed three distinct pathways co-opted by intestinal pathogens to modulate host metabolism. Pseudomonas entomophila, a bacterium originally isolated from flies, causes a lethal infection when ingested (Liehl et al., 2006). By contrast, Pectobacterium carotovorum strain 15 (Ecc15) induces a strong innate immune response when ingested, but does not kill the fly (Basset et al., 2000). Chakrabarti and colleagues compared the transcriptomes of flies infected with these two bacteria and found that a number of stress response genes were selectively activated in P. entomophila infection (Chakrabarti et al., 2012). In addition, whereas transcription of antimicrobial peptides was greatly activated by infection, expression of a diptericin-lacZ reporter fusion could not be detected, leading the authors to conclude that translation but not transcription was inhibited by P. entomophila. The mechanism of translation inhibition was determined to be the result of phosphorylation of elf2α by the GCN2 kinase and inhibition of the TOR pathway, which is known to activate protein translation. The P. entomophila pore-forming toxin, monalysin, was found to be at least partially responsible for this block in translation. Although a connection between host metabolism and protein translation in the intestine was not explored in this study, we hypothesize that a burst of transcription and subsequent translation is likely part of the intestinal response to the ingestion of dietary nutrients. When this is blocked by an intestinal pathogen, the host metabolic response might be altered such that intestinal nutrients are not optimally utilized. Therefore, a block in protein translation could be a cause of wasting in particular intestinal infections.
The human intestine has evolved to detect and respond to the metabolic waste products of its commensal bacterial inhabitants, and the importance of the host response to these bacterial metabolites in human health and metabolic disease is just beginning to be appreciated (Canfora et al., 2015). Parallel symbiotic interactions between Drosophila and its commensal intestinal microbiota have been identified, although the cell types and receptors that detect these bacterial metabolites have not yet been identified (Shin et al., 2011). We hypothesize that intestinal pathogens contribute to and catabolize metabolites within the host intestine uniquely such that the host response to pathogens is distinct from its response to commensals. However, this aspect of the host–pathogen interaction remains poorly understood and is an area in which Drosophila researchers have made and are poised to make seminal contributions.
In Drosophila, unique metabolites of intestinal pathogens have been reported to activate the host intestinal innate immune system. In particular, Lee et al. determined that the metabolite uracil secreted by Ecc15 is an activator of intestinal transcription of the Drosophila gene encoding the reactive-oxygen-generating protein dual oxidase (Duox) (Lee et al., 2013). Based on the signaling pathway mediating duox activation, they proposed the existence of a GPCR that responds to uracil (Lee et al., 2015). Furthermore, they reported that this metabolite is also secreted by the intestinal pathogens Vibrio fluvialis, Shigella sonnei, Pseudomonas aeruginosa and Serratia marcescens but not by the commensal organism Commensalibacter intestini when cultured in minimal medium. Notably, Klebsiella pneumoniae, which is a normal inhabitant of the human intestine, also produced uracil in culture. Because essential metabolic pathways of bacteria are highly conserved, we propose that commensal bacteria and pathogens could differ primarily in how these metabolic pathways are regulated within the intestinal environment, resulting in differences in the repertoire of metabolites produced. Although the Lee et al. study did not specifically study the effect of Duox activation on host metabolism, we predict that the resulting activation of a non-specific intestinal innate immune response, which decreases the number of pathogenic and commensal bacteria, could result in disruption of host metabolic homeostasis.
Another example of the interaction of host and pathogen metabolisms was discovered by Hang et al. (2014). In this case, acetate, a metabolite normally supplied to the host by the commensal microbiota, was consumed by the intestinal pathogen Vibrio cholerae, leading to a decrease in insulin signaling, depletion of lipid stores in the fat body and the appearance of large lipid droplets in enterocytes. This metabolic phenomenon is likely due to the observed transcriptional activation of intestinal IMPL2, an inhibitor of insulin signaling (Honegger et al., 2008). Interestingly, overexpression of IMPL2 has recently been implicated in organ-wasting phenotypes (Figueroa-Clarevega and Bilder, 2015 Kwon et al., 2015). This presents an additional mechanism by which intestinal infection could lead to host wasting.
Manipulation of host metabolism by bacterial pathogens could have the added effect of predisposing the host to viral infection. Recently, the Cherry laboratory has demonstrated that insulin signaling protects D. melanogaster against infection by certain viruses, through activation of the MAPK signaling pathway and phosphorylation of ERK (Xu et al., 2012,, 2013). This supports the hypothesis that, by suppressing insulin signaling, bacterial infection of the intestine might predispose the host to viral superinfection.
The metabolites of commensal intestinal bacteria are sensed by enterocytes, enteroendocrine cells, and possibly cells of other types in the intestine. The host responds to these bacterial signals by adjusting carbohydrate and lipid metabolism. Wasting in the setting of intestinal infection, which has been documented in both humans and Drosophila, is likely to be partially the result of pathogen interference with these ‘conversations’ between the host and its intestinal microbiota. Studies of this phenomenon in Drosophila have revealed a variety of mechanisms by which pathogens interrupt this communication (Fig. 3). Intestinal pathogens might secrete toxins that block the host translational response to bacterial signals. They might activate the innate immune response leading to a shift in the commensal population and, therefore, the bacterial metabolites produced by this population. Finally, they might silence the communication by consuming the metabolites secreted by the commensal population. The benefit to the pathogen of silencing the host–commensal communication has not yet been explored. However, these studies suggest the hypothesis that disruption of intestinal nutrient transport and metabolism leaves more dietary nutrients in the intestinal lumen. These nutrients are available to the luminal pathogen to support its growth and replication. In other words, the host wastes while the intestinal pathogen feasts.
Antibiotics May Kill Off Healthy Bacteria in the Gut
MONDAY, Nov. 17, 2008 (Health.com) — Most of the bacteria that live in a healthy person’s intestines will bounce right back after they&aposre killed during an antibiotic attack, according to a new study.
But several types are wiped out by a course of Cipro, or they survive only in much smaller numbers, reports Stanford University&aposs Les Dethlefsen, PhD, and his colleagues in this month’s issue of the journal PLoS Biology.
Overall, about 30% of the bacterial types found in the intestine showed dramatic population changes after a course of ciprofloxacin. The majority of bacteria rebounded four weeks later.
“We have no idea what the consequences of that are,” Dethlefsen says. None of the three healthy volunteers participating in the study got sick, but the alteration of their bacterial ecosystem could have longer-term, subtler effects, he adds.
The bugs in human guts are a hot topic these days. Probiotics can be used to colonize the intestines with “good guy” microbes. While the jury’s out on whether these supplements have any effect on the gut’s bacterial environment, it is clear that not having a thriving microbial community in one’s intestines can be dangerous, with consequences ranging from a day or two of diarrhea to life-threatening infection with a nasty bug called Clostridium difficile, which can gain a foothold in patients treated with antibiotics.
“We have a very complex, diverse microbial community that lives in our guts and does all kinds of amazing things for us,” Dethlefsen says. Not only do bacteria help to digest food and extract nutrients from food, but they also protect from infection, help regulate the immune system, and may even have a say in the timing of birth.
In the current study, Dethlefsen and his team used a technique called pyrosequencing to take a microbial head count from the stool samples of study participants before they took a short course of ciprofloxacin then researchers took four more samples over the following eight months. The technique involves reading a specific section of genetic material from every one of hundreds of thousands of microbes, making it possible to identify many of the thousands of different organisms present in the gut and determine their relative abundance.
The researchers spotted up to 5,700 bacteria types in each person before the antibiotic was administered. After the volunteers took Cipro, the gut-bug populations looked a lot different. Overall, 30% of the bacterial types showed dramatic changes in their population. One volunteer in the study had an 82% reduction in the diversity of his gut microflora one had lost 63% the third had lost 36%.
However, within four weeks, study participants’ gut bacteria diversity was back to normal.
“That the community can be severely perturbed and then bounce back is very encouraging,” notes Dethlefsen, adding that the findings show there’s probably no reason for healthy people to 𠇏reak out” about the effects of antibiotics on their digestive systems. The fact that the volunteers had no digestive problems despite the profound alteration in their gut bacteria suggests that other bacteria took over the jobs of the missing bugs until their population rebounded, he explains.
Still, the health effects of obliterating certain bacteria with a short course of Cipro—which is generally considered to have a relatively benign effect on digestive system bacteria𠅊re unknown, Dethlefsen says. None of the bacteria that were wiped out, or whose populations were sharply reduced, have any known effects on human health, he adds.
“To me, this looks like a very early step in a whole line of research that can really help us understand what are some of the driving forces in developing antibiotic-related diarrhea, in general, and C. difficile,specifically,” says Marya Zilberberg, MD, a professor at the University of Massachusetts, in Amherst, whose research has helped show that C. difficile infections are becoming more common𠅊nd more deadly—in the United States.
Using the technique, it might be possible to identify certain bacterial strains that protect against C. difficile infection, and others that might make a person more vulnerable, according to Dr. Zilberberg. “This is just a very small cog in a large wheel," she says. "It’s an important cog, but it’s not close to the consumer yet.”
In the meantime, Dr. Zilberberg thinks that the findings confirm that it’s crucial to be an ucated consumer” when it comes to antibiotics. 𠇍on’t say yes to a prescription of antibiotics unless you’re convinced that you really need those antibiotics, because they’re not without risk,” she says.
Dale Gerding, MD, a professor at Loyola University Chicago, agrees: “The message is one that we’ve been saying for a long timeore you take an antibiotic, make sure you need it.”
Previous research had suggested that there were maybe 500 bacterial species in the intestines, but more sophisticated techniques are now showing that there are more. Dr. Gerding also says that it had long been suspected that antibiotics destroy some beneficial bacteria, which is why some people became vulnerable to C. difficile.
𠇊ntibiotics should not be used casually simply because there doesn’t seem to be a downside,” he warns.
Researchers Find Performance-Enhancing Bacteria in Gut Microbiome of Marathon Runners
In a study published online in the journal Nature Medicine, an international team of researchers identified a link between members of the bacterial genus Veillonella and athletic performance. The scientists observed an increase in abundance of Veillonella in marathon runners and isolated a strain of Veillonella atypica from their samples. They also found that Veillonella metabolize lactic acid produced by exercise and convert it into propionate the human then body utilizes that propionate to improve exercise capacity.
Scheiman et al found Veillonella bacteria in the microbiome of elite athletes. Image credit: Composita.
“Having increased exercise capacity is a strong predictor of overall health and protection against cardiovascular disease, diabetes, and overall longevity,” said Dr. Aleksandar Kostic, a researcher at Joslin Diabetes Center and Harvard Medical School.
“What we envision is a probiotic supplement that people can take that will increase their ability to do meaningful exercise and therefore protect them against chronic diseases including diabetes.”
To identify gut bacteria associated with athletic performance, Dr. Kostic and colleagues recruited athletes who ran in the 2015 Boston Marathon, along with a group of sedentary individuals.
The researchers collected samples during a time span of one week before the marathon to one week after the marathon.
They then analyzed the samples to determine the species of gut bacteria in both cohorts.
“One of the things that immediately caught our attention was this single organism, Veillonella, that was clearly enriched in abundance immediately after the marathon in the runners,” Dr. Kostic said.
“Veillonella is also at higher abundance in the marathon runners than it is in sedentary individuals.”
They confirmed the link to improved exercise capacity in mouse models, where they saw a marked increase in running ability after supplementation with Veillonella. Next, they wanted to figure out how it worked.
“As we dug into the details of Veillonella, what we found was that it is relatively unique in the human microbiome in that it uses lactate or lactic acid as its sole carbon source,” Dr. Kostic said.
Lactic acid is produced by the muscles during strenuous exercise. The Veillonella bacteria are able to use this exercise by-product as their main food source.
“Our immediate hypothesis was that it worked as a metabolic sink to remove lactate from the system, the idea being that lactate build-up in the muscles creates fatigue,” Dr. Kostic explained.
“But talking to experts in the exercise physiology field, apparently this idea that lactate build-up causes fatigue is not accepted to be true. So, it caused us to rethink the mechanism of how this is happening.”
Dr. Kostic and co-authors returned to the lab to figure out what could be causing the increase in exercise capacity.
They ran a metagenomic analysis, meaning they tracked the genetics of all the organisms in the microbiome community, to determine what events were triggered by Veillonella’s metabolism of lactic acid.
They noted that the enzymes associated with conversion of lactic acid into the short chain fatty acid propionate were at much higher abundance after exercise.
“Then the question was maybe it’s not removal of lactic acid, but the generation of propionate,” Dr. Kostic said.
“We did some experiments to introduce propionate into mice and test whether that was sufficient for this increased running ability phenotype. And it was.”
Jonathan Scheiman et al. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nature Medicine, published online June 24, 2019 doi: 10.1038/s41591-019-0485-4