Manipulating Normal Flora

Chad Clancy
Capstone Paper

Manipulating Intestinal Normal Flora to Alter Adipose Content and Rate of Gain in Mammals

The intestines are a non-sterile environment that are lined with foreign bodies that the immune system does not actively eliminate. These foreign bodies have been termed “normal flora” and can be described as the bacterial contents of the intestines. that are representative of a population. The normal flora WITHIN the lumen of the large intestine ARE BENEFICIAL TO THE HOST AND ARE do not have pathogenic AS LONG AS THEY ARE INTACT WITHIN THE LUMEN . effects on the body as long as they are contained within the lumen, and actually provide beneficial services to the host. Normal flora bacteria have been shown to deter pathogenic bacteria colonization of the gut, stimulate normal immune function and provide nutrients (insert sources). The relationship between a human host and the normal flora bacteria can be described as mutualistic symbiotic, in which both the host and the bacteria benefit from the established relationship. While the host receives pathogenic protection, immune stimulation and nutrients, the normal flora are harbored in a stable environment which is constantly replenished with new sources of energy. (THIS LAST PART IS REPEATED FROM ABOVE)
OBESTIRY MAY BE LINKED TO AN ABUNDANCE OF Normal flora.IS THAT WHAT YOU MEAN?) have recently come under scrutiny with their ability to provide nutrients and their possible link to obesity. OBESITY IS A Weight gain is a concern not only for the Western nations and their obesity, but also for and undeveloped nations struggling with starvation. WEIGHT GAIN IS ALSO A CONCERN FOR and even rate of gain in livestock. THE GENOTYPE AND PHENOTYPE OF THE INDIVIDUAL MAY ALSO BE RESPONSIBLE FOR WEIGHT GAIN AND ADIPOSE CONTENT. (SOMETHING LIKE THAT TO TIE THESE TWO SENTENCES TOGETHER SO THEY AREN"T REPEATING THEMSELVES) The relationship between the normal flora lining the intestines and the genotype or phenotype of the individual has yet to be thoroughly established. Manipulating the normal flora bacteria of the intestines could alter the adipose content of individuals and affect the rate of gain in developing individuals.
Normal flora bacteria are established at birth and are passed from the mother to the offspring during the birthing process (Ley et al 2005). The bacterial genera that are known to commonly occupy most populations include Lactobacillus, Bifidobacteria and Bacteroids (Martin et al 2007, Samuel et al 2006). (Insert segue) SHOULD THIS PART BE TOWARDS THE BEGINNING OR IN THE SECTION ABOUT THE TYPES OF NORMAL FLORA, ALSO IS THAT THE ONLY WAY A BABY GETS NORMAL FLORA BACTERIA? I REALLY DON"T KNOW. IF THE PARENT IS LACKING, DOES THIS AFFECT THE CHILD. DOES THE CHILD HAVE TO BE BIRTH VAGINALLY IN ORDER TO ESTABLISH NATURAL FLORA. THIS PARAGRAPH NEEDS TO BE DEVEVOPED. IS A BABIES INTESTINE STERILE BEFORE BIRTH OR DOES BREASTFEEDING ALSO CONTRIBUTE TO NATURAL FLORA?? I AM CURIOUS NOW.)
The use of probiotics has been shown to be beneficial to normal flora populations. Probiotics are any substance that either stimulates the growth of specific microorganisms or introduces a microorganism into an environment for beneficial purposes. Several products on the market readily contain probiotics AS A PRESERVATIVE. One common source of probiotics is any yogurt on the shelf. Probiotics are also commonly marketed in large animal veterinary clinics. (Continue and insert segue.)
NORMAL FLORA DIFFERS BETWEEN SPECIES, INDIVIDUAL AND POPULATIONS. (DO YOU MEAN NORMAL FLORA POPULATION, OR POPLULATION OF PEOPLE?) The collective sum of normal flora differs between species, populations and even on the individual level. NATURAL FLORA BACTERIA VARIES WITHIN POPULATIONS While there is great variance in the ratios of which bacteria are most commonly present within populations, ALTHOUGH there are some standard bacteria that can be found across populations and even across species.(DO YOU MEAN SAME TYPE OF BACTERIA, AMOUNG SAME POPULATIONS AND SPECIES?) Lactobacillus has been shown to be extremely beneficial when colonizing the intestines. Two species of Lactobacillus have been IDENTIFIED isolated with from a wide variety of species showing a relatively stable function within the normal flora colony. L. paracasei has been shown to reduce the colonization of pathogenic bacteria in the intestines. L. rhamnosus has been shown to produce multiple effects within the intestines including prevention of diarrhea, prevention of symptoms associated with irritable bowel syndrome, prevention of atopic eczema and reduction of urinary tract infections (Martin et al 2007). Normal flora contents associated with nutrient digestion include Bifidobacteria, Bacteroids thetaiotaomicron, M. smithii and D. piger THIS IS CONFUSING THE WAY IT IS IN THE PARAGRAPH (Samuel et al 2006). (Insert segue, review for completeness on background.)
GERM FREE ANIMALS MODELS HAVE BEEN USED IN Current research. has focused on utilizing germ free animal models to in order to show the relationship between uncolonized individuals and NORMAL FLORA. the effects of a Normal flora bacterial population once the colonies are established within and individual. BY These experiments utilizeing gnotobiotic models or models that begin with a germ free host and establish a known bacterial flora. (Insert some sort of seguel) IS THIS SENTENCE DONE?
Use ofProbiotics USE has been linked withto higher survival rates of offspring and improved health of offspring after birth. After treating sows with probiotics prior to birthing, there was shown to be a 6.1% decrease in mortality rate of offspring. The occurrence of diarrhea also dropped 17% in proboitc treated offspring (Taras et al 2005). Similar results were shown in rat models. Pregnant rats treated with probiotics saw a 15.3% decrease in offspring mortality accompanied with significant increase in birth weight (Anukam et al 2005).
Research has also been conducted on bird models WERE ALSO USED. When selecting for the Lactobacillus biota in the intestines of chickens, there was a 10.7% increase in weight gain compared to a control group. These results were accompanied with an increase in the viable Latobacillus agilis population in the stool (Lan et al 2003). Other research on chickens has shown that for a probiotic to be effective in chickens, the probiotic bacteria must originate from a chicken host (Timmerman et al 2006).
Fat storage has been linked to the bacterial contents of the gut. Colonizing germ-free mice with normal flora from conventional mice showed a 60% increase in body fat content accompanied with a decrease in food consumption (Bäckhead et al 2004). (continue somehow on this and segue…) WOULD THIS PART FIT IN WITH OBESITY? NEXT PARAGRAPH
Substantial research has been done in obesity and normal flora relationships in mice. A correlation has been shown in the ratios of specific colonies and the obesity of the host. While all mice used were colonized with the same normal flora from their mother, differing ratios of these bacteria occurred resulting in either obese or lean mice. Lean mice showed an increase in the quantity of Bacteroides accompanied with a decrease in Firmicutes (Ley et al 2005). Interestingly, this research was performed on genetically modified mice with a modified genotype to either be obese or lean. These results do not necessarily show that the ratio of Bacterioides and Firmicutes is the directly affecting the obese phenotype, but perhaps that the genotype is selective towards harboring one bacterial species over another. It is also possible that the obesity is the selective factor and obesity results in an environment more selective toward one species over another (Ley et al 2005).
Other obesity studies have focused on diet-induced obesity. Germ free mice fed a “Western-style” diet consisting of a high fat and sugar-rich foods were protected from obesity. Their lean phenotype was shown to be accompanied with the increase in phosphorylated AMP-activated protein kinase, an activator of fatty acid oxidation (Bäckhead et al 2007). Oxidation of fatty acids decreases adipose deposits in the body and provides an alternative energy source to glucose in the cells.
An obesity epidemic has begun to spread across the world and researchers have begun to look for plausible options for treating and preventing this debilitating condition. Options for treating obesity are limited and can become even more limited depending on the condition of the individual. Surgery to minimize stomach size is an invasive operation and often a last option for individuals. This surgery can only be performed on individuals in a healthy enough state to withstand the surgery. Limiting calorie consumption works in theory, but convincing individuals who have consumed large amounts of calories for extended periods of time to cut back on calories can often be challenging. Increasing exercise may be a difficult task for those who have achieved an extreme state of obesity and have limited mobility.
Research has shown that at least 10% of our caloric intake is based upon products of bacterial fermentation within our the gut (Samuel et al 2006). These additional calories are derived from processed polysaccharides which are unavailable for human consumption until broken down by bacteria. These polysaccharides are an inadequate source of nutrition without bacteria due to humans lacking the correct enzymes to properly digest them (Sonnenburg et al 2006). If this source of enzymes providing additional calories could be removed from the diet, it is possible to continue to ingest these polysaccharides without utilizing them for fat production. COULD YOU EXPLAIN THIS BETTER? This could effectively lower calorie consumption without affecting the diet of the individual.
The problem with selecting against normal flora bacteria that provide nutritional benefits to the body is how to select against one bacterial species while maintaining a viable population of bacteria that promote normal immune function and provide protection against pathogenic infection. PREVALENCE OF ONE BACTERIA OVER ANOTHER POSES A PROBLEM BECAUSE ….Removal of the entire contents of the gut to re-establish a normal flora lacking polysaccharide-digesting bacteria leaves the host susceptible to pathogenic infection. SHOULD THIS BE IN THE PARAGRAPH ABOUT THE ENZYMES?
DUE TO WAR AND DROUGHT, STARVATION IS SEEN IN MANY THIRD WORLD COUNTRIES. The inverse of obesity in wealthy Western nations would be starvation due to war and drought throughout third world nations. Refugees and poor inhabitants of these nations rely largely on aid, composed of carbohydrate rich food, to survive these terrible conditions (insert source). In an area stricken with war or famine, there is a minimal amount of food available and therefore a minimal amount of free energy available to people. With the knowledge that polysaccharides (a major component of most carbohydrate rich foods) can be broken down by nonpathogenic bacteria, it could be possible to develop a probiotic largely composed of bacteria specified to efficiently convert carbohydrate rich diets into useable monosaccharide units for the host.
A large portion of available polysaccharide rich foods goes to development of food animals. Livestock such as cattle and hogs require a large quantity of polysaccharide rich foods to maintain weight and developing animals require an even larger quantity to yield a high rate of gain necessary for farmers to make a profit.
Utilizing a probiotic with known contents of bacteria could increase yield by not only providing beneficial polysaccharide digesting bacteria, but also providing pathogenic preventing bacteria. This could cut costs to farmers by providing less feed per head of livestock (or putting more livestock on less land) and reducing costs of medical care for animals by reducing bacterial infections derived from the gut.
Directing probiotic research towards animal production could have far reaching benefits. Not only could farmers benefit from reduced costs of raising livestock, but also these savings could be passed on to consumers. Meat is a staple in Western Civilizations, but essential amino acids are provided in other ways to poor developing nations. Reducing the cost of raising cattle in these countries could provide a wider market for meat in these developing nations. Limiting the feed intake necessary to produce livestock also provides a wider market for grain or could make land available to produce products for human consumption. These factors together could decrease starvation and malnutrition across the globe.
Normal flora bacteria are an essential component to a fully functioning organism, not only to the digestive system, but also to the immune system. The mutually beneficial relationship that has coevolved between animal hosts and bacteria has been shown to carry an advantage in maintaining fat deposits, promoting healthy immune function by preventing pathogenic infection and promoting sampling of intestinal contents. Promoting specific populations of normal flora has the potential to increase normal flora benefits within the host. IS THIS IN THE RIGHT SPOT? IF THIS IS THE CONCLUSION, I DON"T REMEMBER READING PRIOR TO THIS POINT.
Current research is focusinges on specifying the SPECIFIC role of individual species of bacteria within the normal population. (POPULATION OF WHAT OR WHO?) Research has shown that manipulation of flora is possible, but may be dependent ing upon multiple factors. One factor may be uncontrollable, genetics. While related mice were shown to carry the same bacteria, the concentrations of certain bacteria were correlated to the obesity genotype of the individual. (increase content here.) ??WHERE ARE THE SEVERAL FACTORS?
Manipulating current populations of normal flora may be a difficult task, but could be more beneficial than detrimental to the host. Promoting certain species within the normal flora population could alter the available calories from the host’s normal diet. Promoting species that readily catabolize polysaccharides into smaller, digestible monosaccharides could provide more calories for an individual struggling to incorporate enough calories into their diet, or increase the rate of gain in livestock animals. Selecting against these very same bacterial species could eliminate a source of calories for an individual struggling to lose weight in order to achieve a healthy lifestyle. Developing probiotics that are capable of selecting for or against these traits could change our current medical views of microorganisms, and their roles in maintaining a healthy body.


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