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The Gut Microbiome and Ingested Selection Pressures

David LA, Maurice CF, et al. . 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature [Internet]. [cited 2014 Sept 14] 559-563. Available from: http://www.nature.com.proxy.lib.ohio-state.edu/nature/journal/v505/n7484/full/nature12820.html

Research was done to determine whether quick changes could occur in the gut microbiome when subjects consumed all plant or all animal diets. Results showed that consuming an all animal diet drastically changed the microbiome after only a day. The all vegetable diet had less of an effect.

Dethlefsen L., Relman DA. 2010. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS [Internet]. [cited 2014 Sept 14] 108. Available from: http://www.pnas.org/content/108/Supplement_1/4554.full

It has been known for a while now that antibiotics have been causing problems for the human microflora. This study looks at the effect of antibiotics on the gut microbiome and how it responds. It appears that the gut is able to bounce back but not to its full strength. Overuse of antibiotics has been leading to a rise in the number of antibiotic resistant bacteria which is a cause for concern.

Khosravi A., Mazmanian SK. 2013. Disruption of the gut microbiome as a risk factor for microbialinfections. Current Opinion in Microbiology [Internet]. [cited 2014 Sept 14] 16: 221-227. Available from: http://journals.ohiolink.edu.proxy.lib.ohio-state.edu/ejc/pdf.cgi/Khosravi_A.pdf?issn=13695274&issue=v16i0002&article=221_dotgmaarffmi

Antibiotic resistant drugs are becoming a major problem. One of the front-runners of this issue is Clostridium difficile an inhabitant of the gut microbiome. This article demonstrates that interfering with the natural gut microbiome can lead to increased rates of infection and antibiotic resistant bacteria.

Kurukawa K., Itoh T., et al. 2007. Comparative Metagenomics Revealed Commonly Enriched GeneSets in Human Gut Microbiomes. DNA Research (14) [Internet]. cited 2014 Sept 14] 169-181. Available from: http://dnaresearch.oxfordjournals.org/content/14/4/169.full.pdf+html

This study looks at fecal samples of 13 Japenese individuals of different age, including unweaned infants. The goal was to determine characteristics common to all gut microbiomes, along with those that vary from person to person. Researchers discovered that the functions of the bacteria overall were similar regardless of the age or age of the individual, excluding the infants who were still breastfeeding.

Verstraete W., Aidy SE, et al. . 2013. Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome. Microbial Biotechnology[Internet]. [cited 2014 Sept 14] 6(4): 335-340. Available from: http://www-ncbi-nlm-nih-gov.proxy.lib.ohio-state.edu/pmc/articles/PMC3917468/

Loss of helpful gut bacteria is becoming a major problem with the overuse of antibiotics killing off lots of the good bacteria. This article demonstrates some examples of ways to restore lost microbes, such as prebiotics and fecal transplants.

DUE OCTOBER 1ST Suggestions to make this page more informative:

Describe the functions of the gut and its various parts
Mention all of the components that make up the gut (small intestine, large intestine, caecum, anus) Include links to all of these which have wikipedia pages. Could also discuss the function of the gut (what it does, how it performs its function). Mention where it's located in the body.

Gut Microbiome
Get down to the microscopic level and talk about the gut microbiome and what types of bacteria are the most prevalent, most harmful, most beneficial. Discuss how there are three main groups of gut microbes in humans

Effects of Microbiome on Body
Discuss what effects the gut microbes have on the body (Those that are symbiotic and how, which cause diseases, which have no effect).

Diet
Talk about how what you eat effects your body and your gut microbiome. What types of foods can cause changes to the normal microflora

Brandel.23 (talk) 01:41, 30 September 2014 (UTC)Brandel.23

https://en.wikipedia.org/wiki/Gut_(anatomy)

Zimmer, C. (2011, April 20). Bacterial Ecosystems Divide People Into 3 Groups, Scientists Say. Retrieved September 30, 2014. Available from: Zimmer, C. (2011, April 20). Bacterial Ecosystems Divide People Into 3 Groups, Scientists Say. Retrieved September 30, 2014.

FINAL EDITS

https://en.wikipedia.org/wiki/Antibiotic_resistance

(Once a bacterium becomes resistant to an antibiotic, it is unable to return to its previous state of vulnerability. Resistance will be passed on to all of the daughter cells of the resistant microbe.)

(By definition, probiotics are “A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance” Treatment works by ingesting an encapsulated pill filled with helpful microbes. Once these organisms reach the gut, they replenish the beneficial bacteria that were wiped out due to antibiotic use. The microbes also apply niche competition to the harmful microbes trying to colonize the body, helping to prevent the occurrence of an infection. A stool transplant works by taking the feces from a healthy individual and inserting it into an individual who has an infection. There are three methods in which this treatment can be administered. The mixture can be applied to the top of the small intestine by insertion of a tube through the mouth or nose, applied in the colon during a colonoscopy, or by using an enema in the lower end of the colon. This allows for healthy bacteria to be reintroduced to the gut microbiome. This is another method of introducing natural, beneficial bacteria back into the body and eradicating the harmful microbes.)

(Alternating therapy is a method in which two or three antibiotics are taken in a rotation versus taking just one antibiotic so that resistant bacteria do not have time to arise and colonize the gut. Studies have found that this method reduces the rate at which antibiotic resistant bacteria arise in the gut better than if an individual took a single prescription for its entire duration. While this treatment does not completely terminate the antibiotic resistant bacteria, it does delay its onset which allows researchers more time to find and develop a more permanent cure.)

FINAL DRAFT STARTS HERE

The Gut Microbiome and Antibiotic Resistance

The gut microbiome consists of all the bacteria present in the stomach and intestines of the body. It is made up of thousands of different microorganisms, and is changing all the time. Everything that passes through the gut can alter the amounts and types of bacteria present, especially medications. This can have both a beneficial and a harmful effect on the body, depending on how selection acts in the gut. There are a few different selection factors when it comes to the types of organisms that are present in the body. Natural selection plays a major role in the types of organisms that remain in the gut. The body selects for cells which are helpful or those that have a commensal relationship, and selects against those that are harmful or parasitic. Natural selection also acts upon the organisms present in the gut. This means that those bacteria which are best suited to live in an acidic gastrointestinal environment, regardless of benefits or detriments, are going to be chosen over those that are not as well suited. Cells that are able to survive attempts to remove them are going to be selected over those who are susceptible to the efforts. Antibiotics are another major factor when it comes to determining which types of cells get to stay in the gut. Bacteria wiping medicines are not able to distinguish the bad bacteria from the good. This is an issue because antibiotics have a major effect on the environment of the gut. Not all selection pressures are beneficial to the host, and products that are meant to help can end up harming. Modern day medicine has become a major issue for the gut microbiome. Since the introduction of penicillin during World War II, antibiotics have been used to cure a myriad of illnesses. While this has been an incredible step in the area of healthcare and pharmaceuticals, it has created a bigger problem than the one it is curing. Antibiotics are being prescribed to cure everything from urinary tract infections to the common cold and patients are not finishing the medications as prescribed (Kollef and Fraser 2001). This has led to the evolution of antibiotic resistant bacteria. These arise when a cell undergoes a mutation which gives it the ability to be unaffected by antibiotic treatments. This resistant cell is then selected for and becomes abundant in the body, making treatment with that specific medication moot. Antibiotic overuse has resulted in many combinations of medicines that are no longer effective at removing disease-causing bacteria, and some infections are almost untreatable (Anderson 2003). An arms race is developing between pharmacists and bacteria as one is always trying to best the other. As soon as a new vaccine is discovered, researchers almost immediately start looking for another treatment for when the previous one is no longer effective (Kollef and Fraser 2001). Resistant bacteria are developing faster than we are able to make medications to fight them (Kim Lieberman and Kishony, 2014). Medical experts are currently studying new ways to counteract the effects of antibiotic-resistant bacteria without having to develop new medications, or at least extend the shelf life of present day medications. This is the future of medicine, as once resistant bacteria are selected for in a population, they are unable to go back to their previous state of being affected by a certain medication (Anderson 2003). Alternative methods of treatment are going to be a necessity in the coming day and age. There are currently many treatments that have the potential to cure diseases and infections without the need to develop new antibiotics. Reducing the use of these medications would help to decrease the number of resistant bacteria in the body, as cells with lower mutation rates tend to have a higher fitness than those who mutate more frequently (Arjan and de Visser, 2002). This means that those microorganisms which mutate at a higher frequency and perpetrate antibiotic resistance would die out as they are less fit to live in an antibiotic-free environment. Eradicating them would lead to fewer illnesses and shorter hospital stays. To combat these microbes, there are three major treatments that are being studied and utilized presently: probiotics, fecal transplants and alternating therapy. Each of these methods is gentler on the body than developing new, harsher antibiotics. They slow down, or eliminate altogether, antibiotic resistant bacteria. Alternative therapy is the least desirable of the three treatments, but it allows for more time to study the resistant bacteria and find a new, better treatment. Fecal transplants and probiotics are more natural and easier on the body. These are the treatments of the future, the methods that are going to wipe out dangerous bacteria. Of the three major treatments that are being studied and implemented, probiotics are one of the more natural solutions. By definition, probiotics are “A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance” (Fuller 1992). Typically probiotics come in a pill form, enclosed in a capsule, and are taken orally. They reach the gut where they replenish any natural bacteria that may have been wiped out by antibiotics or harmful bacteria. It is currently believed that there are three main bacterial communities, enterotypes, in humans. An enterotype is the name given to the microbial population in the gut, based on its most prevalent species. The three main types are Bacteroides (enterotype 1), Prevotella (enterotype 2) and Ruminococcus (enterotype 3) (Raes, et. Al 2011). This is a major finding as it could lead to a more personalized type of medicine. Currently everyone receives the same types of probiotics. This leads to different health results in different individuals as the bacteria present in probiotics may not be the ones their bodies require. Once the various enterotypes are studied more in depth and confirmed, medicine can become more personal and people with certain enterotypes will be given probiotics that will replenish their gut microbes that were lost to detriments such as antibiotics. Eventually probiotics could be used as a form of treatment instead of as a supplement to harsh antibiotic treatments. Another form of treatment that is being studied right now is fecal transplants. Fecal transplants work by taking the feces of a healthy individual and inserting it into an individual who has an infection. There are three methods in which this treatment can be administered. The mixture can be applied to the top of the small intestine by insertion of a tube through the mouth or nose, applied in the colon during a colonoscopy, or by using an enema in the lower end of the colon. This allows for healthy bacteria to be reintroduced to the gut microbiome. Fecal transplants have been used to cure individuals infected with Clostridium difficile related diseases (Van den Abeele, et al 2013). A study conducted on individuals infected with C. difficile resulted in 94% of those treated with transplants being cured, while only 31% of patients treated with vancomysin, the strongest C. difficile fighting antibiotic, were deemed cured (van Nood et. al 2013). This could be a major turning point as C. difficile is a very antibiotic-resistant microbe and can only be killed by the strongest of antibiotics, which cause serious damage to the natural microbial population. It appears that a pill form is in the works and works just as well as the other forms of administration (Worcester 2013). If this pill is able to be mass produced, C. difficile could be wiped out in no time, and gut bacteria would stay healthy and abundant. This method could then be used to try and cure other hardy hospital infections as well, as it could remove the harmful bacteria from the body permanently. The third major area of study to reduce the rise of antibiotic-resistant bacteria is through alternating therapy. This is a method in which two or three antibiotics are taken in rotation versus taking just one antibiotic so that resistant bacteria do not have time to arise and colonize the gut. By creating an environment that is more conducive to the natural gut bacteria, researchers are practicing artificial selection. They are choosing which bacteria are allowed to be present in the cell, and those which they want to be wiped out. It has been proven effective in reducing the rate of resistance evolution in bacteria. A study was conducted to see whether the most antibiotic-resistant bacteria developed when using a single antibiotic, taking a bunch of antibiotics at once, or alternating between two antibiotics. It was found that all of the alternating treatments were more effective than the single antibiotic at slowing the rate of resistance mutations. When compared to the antibiotic cocktail, they were equally as effective. The alternating treatment is overall a better choice though as taking more than one antibiotic at a time can result in toxic side effects, especially when taken for an extended period of time (Kim, Lieberman and Kishony, 2014). If a patient were given the option between the two treatments, the alternating therapy would be the better option overall. While this method prevents bacteria from mutating into resistant strains, it does not prevent the good microbes from being eliminated as well. Antibiotic-resistant bacteria are currently a major issue in the United States. They are developing faster than we can come up with a new medication to fight them. Natural selection is also aiding in the survival of the resistant microbes as they have a higher fitness than their non-resistant counterparts. This is why it is important to find other methods of combating infections. Using treatments such as probiotics and fecal transplants allows for the complete removal of antibiotics all together, along with keeping the natural gut microbiome in its normal state and preventing the development of antibiotic resistance. Alternating therapy is a step in the right direction. It does not eliminate antibiotics or protect the gut microbiome from being disrupted, but it does slow the development of resistant bacteria, which allows more time for new medications and treatments to be studied. These treatments could help put an end to the arms rrace that is constantly being waged between then human body and harmful microbes, and create a healthy gut environment.

References Anderson D. 2003. Persistence of antibiotic resistant bacteria. Current Opinion in Microbiology                  6(5):452-456. Arjan J., de Visser GM. 2002. The fate of microbial mutators. 148(5):1247-1252. Fox JL. 2013. Fecal transplants to follow FDA rules. Nature Biotechnology 31:583. Fuller R.. 1992. Probiotics: History and development of probiotics. The Scientific Basis. Kim S., Lieberman TD, Kishony R.. 2014. Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance. PNAS 111(40):14494–14499. Kollef MH, Fraser VJ. 2001. Antibiotic Resistance in the Intensive Care Unit. Annals of Internal Medicine 134(4):298-314. Raes J., Pelletier E., et. al. 2011. Enterotypes of the human gut microbiome.. Nature 473(7346): 174-80. Van den Abbeele P., Verstraete W. et. al. 2013. Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome. Microbial Technology 6(4): 335–340 van Nood E., Vrieze A., et. al. 2013. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. The New England Journal of Medicine 368:407-415. Worcester S.. 2013. Fecal transplant pill targets C. difficile infection. Family Practice News 43:17.