In 2007, the Human Microbiome Project — an international effort to characterize the microbial communities found in the human body and to identify each microorganism’s role in health and disease — was launched. As a result of this effort, our understanding of the human microbiome expanded appreciably and, in the past few years, we’ve come to fully appreciate how beneficial our microbiome is to us. Made up of dynamic communities of trillion microbes, the microbiome consists of eukaryotes, archaea (primitive single-celled organisms), bacteria and viruses that reside on and in our bodies. These microbes complement each other and the human host, and play important roles in a variety of biological processes. Indeed, 0ur microbial partners carry out a number of metabolic reactions that, although not encoded in the human genome, are necessary for human health. Thus, the microbiome may represent a newly recognized organ, capable of a great variety of metabolic activities.
The microbes that make up the microbiome inhabit not just the gut and areas directly exposed to the outside world, but also parts of the body that were long assumed to be microbe-free, such as the placenta, which turns out to harbor bacteria most closely akin to those in the mouth. The mouth microbiome is also suspected of influencing bacterial communities in the lungs, the penis, the vagina, and the skin.
It is not surprising, then, that our current perception of human health is influenced by the increasing appreciation of the microbiome, resulting in the development of novel approaches for the prevention and treatment of different diseases. A recent study highlights the importance of the gut microbiome in promoting immunity to vaccination and provides an outstanding example of how understanding the microbiome can help in the prevention of infectious diseases.
The study (TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination) shows that antibiotic treatment given before or during vaccination may impair immune responses to vaccines by depleting the intestinal microbiome . Bali Pulendran, lead author of the study, said in a press release: “Our results suggest that the gut microbiome may be exerting a powerful effect on immunity to vaccination in humans, even immunity induced by a vaccine that is given at a distant site.”
In previous studies, Pulendran and his collaborators observed a strong correlation between high expression levels of the gene encoding Toll-like Receptor 5 (TLR5) and a strong antibody response to the influenza virus in vaccinated individuals. TLR5 encodes a protein that enables immune cells to sense flagellin, the main structural protein for the whips (flagella) many bacteria use to propel themselves. By interacting with TLR5, flagellin triggers the immune system to generate effective responses to infectious microbes.
The new study shows that the sensing of flagellin by cells of the immune system is a critical component affecting vaccine responses in mice. Mice treated with antibiotics and germ-free mice mount reduced immune responses to the flu vaccine when compared to mice with an intact microbiome. Mice still colonized with bacteria but lacking TLR5 exhibit reduced immune responses, similar to those observed in antibiotic-treated and germ-free mice. Oral reconstitution of antibiotic treated mice with bacteria containing flagellin, but not with mutant bacteria lacking flagellin, could restore the decreased antibody response.
Pulendran added: “These results demonstrate an important role for gut bacteria in shaping immunity to vaccination, and raise the possibility that the microbiome could be harnessed to modulate vaccine efficacy. The key question is the extent to which this impacts protective immunity in humans.”
Below is a fun overview of our microbiome (The invisible universe of the human microbiome) from National Public Radio!
Society as a whole has a negative outlook on the microorganisms that inhabit our bodies, which has lead to an obsession of disinfection. Unfortunately, as the video said, that has lead to the loss of our microbial flora. However, recently, there has been an increased use of probiotics. Yogurts now proudly label that they have billions of live cultures, and there has been a push to stop people from constant use of antimicrobial soaps. One interesting note about the video was that they mentioned that sometimes the native microbes can expel their own antibiotics. I decided to look more into this and to get an example of this happen and I came across an article that discusses a filamentous bacterium of the genus Streptomyces that produces an antibiotic specific to the parasite Escovopsis. It would be interesting if we researched the molecular formula of the antibiotics the microbes produced themselves and instead of using the antibiotics we use now, that kill everything, we used antibiotics that had a specific target.
On a different note, as the video stated, another reason why the amount and variety of our microbial colonies are decreasing are due to the increased C section operations and the decrease in breast feeding. Sometimes, the mother has no choice but to have a C section or to not breast feed. However, while researching baby supplements, I came across a relatively new product: Lactobacillus reuteri fortified formula, which is added to treat diarrhea, and has also been found to decrease crying and increase sleep time for babies.
Everything in life requires balance or some form a homeostasis. I see no problem with disinfecting, use of antimicrobials, and keeping the body clean. Just as there is numerous microbiome that research has found to be useful in fighting invading pathogens in the body the are a number of opportunistic pathogens waiting for our immunological defenses to let down.
I say ‘ a new world’ requires new actions! There are a lot of things that are done differently in more industrialized nations. For instance, diets are different because most of the food are not freshly picked for cooking because there is no nearby subsistence farming done to encourage healthy eating. Therefore, the last resort is to eat foods that have been stored under colder temperatures for transport, or sometimes even frozen. Callous diets have lead to obesity and unimaginable complications. One reason caesarian sections (c-section) are common is as a result of poor diets and a wide range of fast food restaurants that facilitate poor dietary intake. No wonder the infant cannot develop proper microbiome.
Jason Tetro, a Toronto-based microbiologist with more than 25 years experience in research writes– “relying on one source of food could lead to a higher level of specific bacteria causing disease, as well as inflammation – a process that is particularly common with many foods high in sugar and fat content.” He mentions that it is not necessary to have sugar and fats in one diet. He also states that from a bacterial it is better consume fermented products.
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Future therapeutics, can be derived by using the microbiota especially the one on the human gut as a biomarker to understand the manifestations of diseases inside and outside the gut.
I am not sure a species specific antibiotic, like you’ve suggested, is possible. However, bacteriophages could be used therapeutically to get rid of resistant strains of bacteria such as MRSA and VRSA in hospital settings, where such infections are likely to occur. The Eliava Institute specializes in this type of research. They have been using phage therapy since WWII. There are many benefits to phage therapy but many in the U.S. are opposed to it because they fear the phage infecting a human, which is not very likely given the specificity with which viruses infect.
Speaking of bacteriophages, I recently came across a documentary about the Ganges river. Even though it’s a very polluted river, the water has an unusually low population of bacteria and microbes, earning it the nickname the holy river from hell. There is definitely enough food for bacteria to grow, and the temperature and oxygen levels should in theory support bacterial life. There are also over 140 species of fish in the Ganges. Even though often times, due to religious rituals, dead bodies are dumped into the river, and people often time use the water to clean their clothes and dishes, European explorers stored the water from the Ganges river because it was the only source of water that would no go bad in long expeditions out at sea. Later on it was revealed that this was due to an unusually high population of bacteriophages. I strongly believe that phage therapy should be utilized in America. It would be interesting to see if bacteriophages could be used instead of chemical preservatives.
I recently learned about the history of phage therapy and found it to be very interesting. It’s discoverer Felix d’Herelle traveled to many places treating diseases such as dysentery, plague and cholera until he co-founded the Eliava Institute for Bacteriology. The main problem in America at the time was that the tension caused by the war caused a sort of embargo on scientific knowledge. Without being able to obtain information from the Eliava Institute the investigations on bacteriophages had to be done from the ground up. The tests performed in America provided inconsistent results and the release of penicillin caused scientific focus to be shifted from phage therapy to antibiotics. I agree that phage therapy should be investigated today but it may face the same problems concerning vaccination: people simply do not like the idea of being infected.
I agree that the world definitely frowns upon microbiota because everyone tends to equate them to germs and germs are bad, right? It is interesting though to utilize more probiotics than antibiotics; I had never really thought of encouraging bacterial growth and function before, but I assume that’s due to what society deemed “clean and helpful.” Using antigen-specific antibiotics produced by bacteria itself would probably serve as much more efficient and natural means of tackling infections. The same idea should be applied to the instance of childbirth and breastfeeding. Emulating and utilizing the bacteria found in the birth canal in formulas can increase a baby’s chances of obtaining the necessary bacteria needed to fight infection properly. In today’s world, a lot of activities are carried out artificially or through some sort of laboratory-enhanced procedure and when it comes to life, there should be means to keep it as natural as possible. Bodies of any and every kind are built to operate a certain way and simply require the proper fuel and nutrition, or in this case, microorganisms. Not to say that advancements in science and medicine have been negative or futile, because we all need a little help, but there is something to be said about integrating the natural way of life and steering clear of a completely artificial way of life.
I believe future studies will prove that the microbiota given to us from our mothers and breastmilk serve as the precursor to our immune system. They may serve to build up the innate, non-specific, immune response by showing us different examples of microbiota such as bacteria, archaea, fungi, and viruses. However, with society’s antimicrobial and clean approach, we may be dampening the innate immune response when outside, harmful microbes make their way into the body. This idea is supported by the study mentioned; the Toll-Like Receptor 5 works best in the mice with full-functional gut microbiota. It serves as a team effort where the gut bacteria is coaching TLR5 on what to except when harmful bacteria enter. When the gut microbiome is depleted via antibiotics, there is less preparedness for TLR5; therefore, there is a reduced response. These studies carry relevantly new information and ideas, but with some unraveling, the many functions and associations to the immune system will be revealed.
If I am interpreting the study correctly, it is essentially saying that our normal microbiota keep immune system active and without the constant activation or stimulation of our immune system by our natural flora we would mount very poor responses to newly introduced pathogens. I had heard of this theory some time ago and I find it interesting that there is evidence that is beginning to support it.
That is essentially what this article is saying! However, the video, along with some other aspects of the article, are highlighting the importance of how humans acquire and sustain their own personal microbiome as well. For example, it was noted that breastmilk and the exchange of microbes from mother to child during birth, was incredibly essential to proper development of not only a newborn’s microbiome, but their health in general. It was also said, during the video, that by preventing children from exposure to microbes and by extension impairing their ability to create their own personal microbiome, many allergies along with asthma have popped up in society and are becoming incredibly important issues. These simple diseases are mere examples of how our body’s immune system needs to be taught to recognize harmful pathogens from helpful bacteria, and thereby mount a proper and efficient immune response that doesn’t damage host tissue. Thus, it is equally important to say that this article was a reminder to all that by allowing ourselves and our children to experience and accept bacteria into our everyday lives instead of being so afraid of common bacteria, mankind can enjoy a fuller, more rich microbiome that supports a grander and more effective immune system!
The Human microbiome and its relation with immune system is very important for a healthy individual. These microbes need good nutritional food and if the food is poor in nutrition the chances of getting ill are higher. According to the United Nation eight Millennium development goals the removal of poverty and hunger are the two of the important which are still pending and has a long path to go.
In anarticle it was mentioned that the growing use of the antibiotics is one of the major cause for the decrease in the Human microbiome, these antibodies affect the human microbiome by interfering the system. These antibodies lead to the cause of various autoimmune diseases and allergies like rheumatoid arthritis, lupus, diabetes and celiac disease. There many other reasons for the decrease in Human microbiome like clean water, caesarean birth and antibacterial soaps usage in modern society.
In the same article it was mentioned about the growing knowledge of microbiome in human and the upcoming use of probiotics and prebiotics. Probiotics is related to fermented ingredients whereas prebiotics is related to the gut microbe. Even the study is going on prebiotics in the breast milk.
In an article in New York Times it was stated that the human microbiome can be seeded before the birth of the child by picking microbe from the mother womb.
I understand that from 2007 to now is a short amount of time in the scientific community. I also understand that not everyone is a college student with recent courses in microbiology and immunology. Yet, if I understand the presentation of the information, antibiotics affect our natural microbiota. This is not new information. It is known that when antibiotics are taken, they kill everything including the good stuff we need. So I do just not fully understand the relevance of the information at this time? I also did not understand fully how oral reconstruction could restore the decreased antibody response of the mice.
I think the problem is that some people do not realize that there are lots of good bacteria that our body needs to function at 100%. The only time a none college student hears about bacteria is when he/she goes shopping for sanitizers and antiseptics, which boasts claims of “kills 99.99% of bacteria” or in the news when they hear so and so bacteria caused so and so disease that killed a billion people. Bacteria have a profoundly negative connotation. So, when people take antibiotics, they think “oh awesome this is gonna kill germs, which is good, cause germs are bad”. The purpose of this article was to bring into light the beneficial properties of some bacteria. Oral reconstruction helped decrease the antibody response of the mice because, to my understanding, the microbes in the mouth helped speed up the antibody response of the mice because those microbes work in unison with the immune system.
In the health conscious society of today, many need to be informed that by cleaning everything they are essentially weakening their immune system. Especially in the infants and youth, small traces of the pathogens such as bacteria and fungi can lead to a more effective immune response later in life, for they will may have memory immune cells that respond faster to the infection, eradicating it more quickly. Scientifically and medically, all bacteria are not bad. The innate, non-specific, immune cells recognizes broad components of pathogens such as the flagella of some bacterium, so something needs to be known about the classes of pathogens which cannot happen if we are constantly killing and avoiding them all.
This was on National Public Radio so it is just meant for the general public, so like how your professors always say know your audience they did just that in the video. Our society has become almost germophobic, disinfectants, hand sanitizers, and antibacterial wipes are abundant pretty much everywhere. Antibiotics are given out pretty easily, especially in agriculture, and people aren’t finishing their dosage regimen as they should often. So people thinks any germs are bad and sterile is good, so they have to show that is really not the case even though it isn’t new information.
And for the mouse its oral reconstitution, not reconstruction, so they were being given flagellin having bacteria. So their immune systems would react to the new bacteria and increase their antibody response to bolster against the new bacteria.
One thing I find interesting from the video was the fact that diabetes, obesity, and other food related diseases are causing the gut microbiota to dissipate and disappear. I think that goes to show what kind of substances are being presented to us as “food” and what we consume on a daily basis may not actually be what we need. Or it could be a reflection of the amount of food intake seen today; but that’s mostly in well-developed countries and typically only America. Another interesting point was that the microbiota did not teach the immune system how to function properly. If this is the case, would it be ludicrous to suggest that in regards to infancy and antibiotics, only certain situations should be deemed severe enough for antibiotic use?
I personally think what’s causing the decrease in gut flora has more to do with the chemicals and preservatives in our food, and not so much the amount of food we eat. According to an Australian study , eating only McDonald’s foods for 10 days, caused the gut flora to decrease from 3,500 to only 1,300 species. His caloric intake remained the same, but due to the chemicals and preservatives added to the food, gut flora diversity decreased significantly. This decrease could cause a plethora of problems, as stated in the comments and in the article. This is pretty interesting because most people stay clear of fast food because they think it’s unhealthy because it’s high in calories. But the preservatives, which were added to stop the growth of bacteria on the food, could stop the growth of healthy bacteria in our guts also. It is interesting to see that it’s not only enough to worry about calories as many people do.
Another post mentioned hand sanitizers which is what I thought of when I read this article. I specifically learned that using hand sanitizers constantly and killing those 99.9% of germs isn’t beneficial because it depletes all the bacteria on your hands, especially some that you may need that actually travel to your intestine and become part of the microbiota there.
This article also reminded me of a treatment that has been used by an advocate of the hygiene theory who placed hookworms on his body to treat allergies. While traveling to a less developed country, he noted that the natives there were not prone to allergic responses like much of the population in the Western world and based on this, he went on to discover that it was because of the overly sterile environment we produce for ourselves here. The vaccinations, the filtered water and the overly clean habits we have are actually leading to an over incidence of immunogenic responses against the harmless of pathogens. We should attempt to maintain a balance between how clean we keep our environment and what we expose ourselves to in order to be in optimum health and doing so will require more research on hygienic practices that are useful versus those that are detrimental.
The microbiome is established at birth via vaginal delivery. The gut is in fact an outside organ as it leads directly to the outside of the body. It plays an influential role in to our health as it assist with our immune system including the development of TLRs, macrophages, dendritic cells, and NK cells. Vaccines further our immunity by increasing the adaptive immune response. This gives us more protection from invaders by being able to recognize pathogens encountered previously.
In my immunology class, we were asked on a few occasions to define the “goal” of our immune system, and each time I stated “to keep the microbiotic environment of the organism as close to the normal makeup as possible.” I stand by my answer. Yet now I know more about it, because these normal microbiota could now be considered a part of our immune system. They have many benefits right? Skin resident bacteria do their job by taking up space literally. They attach and take up real estate on our skin so that harmful pathogens cannot. This occurs on our epithelial cells as well in the gut for instance. I assume finding out why the flagella induce immune cells to begin activating will need to be studied further, especially considering that the immune cells don’t attack normal microbiota at normal levels. They certainly don’t develop antibodies to them either.
Something that the video related that struck my attention was the fact that genetic factors can affect the composition of the microbiome. One study I found (1) showed that monozygous twins (i.e. identical twins) had microbiome compositions much closer to one another than dizygous twins (i.e. fraternal twins), and dizygous twins had a more similar composition than subjects who were unrelated to each other. Since abnormalities in microbiome composition leave people susceptible to various diseases (2), it will be interesting to see future research involving 1) how human genetics affect the establishment of different microorganisms in the microbiome, and 2) how those differences in the genetically-determined compositions affect our susceptibility to various diseases, both chronic and acute.
References:
1. http://www.cell.com/cell/fulltext/S0092-8674%2814%2901241-0
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979869/