# Metabolomics/Applications/Nutrition/Large Bowel Metabolites

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Large Bowel Metabolites

## Introduction to Large Bowel Metabolites

Large bowel metabolism is complex and is vastly affected by what we consume. Certain foods can predispose us to developing cancer, obesity, and cardiovascular disease. Fortunately, there are foods that possess health benefits to counteract these medical maladies. The following articles primarily focus on how consumption of the good foods can alter metabolism within the intestines and result in reversing and preventing adverse effects.
In this article, Insights into the roles of Gut Microbes in Obesity, microbes in the gut play a large role in determining obesity. The relationship between microbiota structure and phenotype uniquely affect body weight. It is shown that gut microbes have a large role in storing energy from the foods we consume in our diet; some of these gut microbes include Bacteroidetes and Firmicutes.
In the article, Protein Degradation in the Large Intestine Relevance to Colorectal Cancer, there is evidence that a high meat and high fat diet can lead to colorectal cancer. Colorectal cancer is the second most deadly disease in western countries. The intake of protein from the high meat diet is detrimental because when the protein degrades, toxic side products are released into the intestine causing damaging effects.
In the article, The Influences of external bacterial on the relationship of intestinal microbiota and human large-bowel metabolism, light is shed on the symbiotic relationship between microbiota of the intestine and metabolism. The byproducts of metabolic processes of microbiota can lead to a synergistic effect involving another microbiota species. The use of probiotics can help promote good health.
The article, Microbiota Conversion of Polycyclic Aromatic Compounds to Estrogenic Metabolites, delves into the effects of large-bowel microbiota on the metabolic transformation of Polycyclic Aromatic Hydrocarbons (PAH) to estrogen metabolites. This current study debunked the hypothesis that colon microbiota used an oxidation reaction to hydroxylated the PAH.
In the article, Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities, we see the importance of consuming dietary fiber. Dietary fibers play a protective role against coronary heart disease by reducing cholesterol. This is accomplished due to the viscosity of dietary/soluble fibers, which interfere with cholesterol absorption.
This article, Absorption and metabolism of octanoate by the rat colon in vivo: concentration dependency and influence of alternative fuels, shows that the intestine can process medium chain fatty acids in addition to short chain fatty acids. This discovery can be used to help treat individuals with compromised small bowels. MCFAs are able to provide 20% of the basal metabolic needs.
In the article, Inhibition by White Tea of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine-Induced Colonic Aberrant Crypts in the F344 Rat, we see the anti-carcinogenic effects of white tea. This study showed that white tea offers an increased level of protection in comparison to green and black tea. White tea is rarely processed and contains high levels of catechins and related polyphenols.
The article, Probiotic Bacteria Influence the Composition and Function of the Intestinal Microbiota, discusses the role of probiotic bacteria on other microbiota in the intestines. There are over a thousand phylotypes of microbiota in the intestines. Typically the microbiota in the host are commensals but with adequate levels of probiotic bacteria and microbiota, health benefits can be observed.
The article, Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults, takes a look at soy consumption and its ability to change isoflavone levels in individuals. Isoflavone is hydrolyzed by the gut lactase phlorizin hydrolase when ingested and releases aglycons, daidzein, geninstein, and glycitein. The study showed that soy consumption had little to no effect on isoflavone metabolism.
In this article, Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans, a study was conducted to further the understanding of the relationship between diverse metabolite arrays and bridge the gap between metabolomics and nutritional science. Although gut microbiota has a relationship with metabolic process, it has little to no effect on metabolic profiles.
The website, Absorption and Metabolism of Isoflavones, discusses the importance of the metabolism of isoflavones. Isoflavones are substances that are attained from soybeans, a non-nutrient food. Isoflavone and the female hormone estradiol are able to superimpose with each other, making them indistinguishable. Due to this ability, isoflavones can fit into the binding domain of the estrogen receptor. There are many clinical applications that can exploit this ability.

## Articles

Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults

### The Influence of Soy Consumption on Plasma Concentration and Excretion of Isoflavonoids

To look at how soy consumption influences plasma concentration and excretion of isoflavonoids.

#### New Terms
##### Isoflavone

    a class of organic compounds, often naturally occurring, related to the flavonoids. (http://en.wikipedia.org/wiki/Isoflavone)

##### Bioavailability

    reaction of an administered dose of unchanged drug that reaches the systemic circulation. (http://en.wikipedia.org/wiki/Bioavailability)

##### Equol

    metabolized from daidzein, a type of isoflavone. (http://en.wikipedia.org/wiki/Equol)

##### Dietetics/Dietitian

    is an expert in food and nutrition. (http://en.wikipedia.org/wiki/Dietitian)

##### Venous

    in the circulatory system. (http://en.wikipedia.org/wiki/Venous)

##### Glycitein

    An isoflavone which accounts for 5-10% of the total isoflavones in soy food products. (http://en.wikipedia.org/wiki/Glycitein)

##### Daidzein

    one of several known flavones. (http://en.wikipedia.org/wiki/Daidzein)

##### Water-acetonitrile

    A polar solvent, miscible with water. (http://en.wikipedia.org/wiki/Acetonitrile)

#### Summary

The study investigates whether chronic soy uptake will change the isoflavone availability of individuals as determined by the levels of concentrations of isoflavone in plasma and urine of the individuals, as well as change in gut microflora activities toward isoflavones.
There is great interest on the contribution of isoflavone on human metabolism. Isoflavone, when ingested is hydrolyzed by gut lactase phlorizin hydrolase, releasing aglycons, daidzein, geninstein, and glycitein. These molecules may be absorbed or further processed into metabolites. For example, daidzein can be converted into equol and O-desmethylangolensin (O-DMA). Gut microflora is important in the metabolism of isoflavones – antibiotics in the gut block isoflacone metabolism and germ free animals do not excrete the metabolites. The gut microflora in human is variable. About 35% of the Western population can produce equol. Dietary modifications have failed to change the equol-producing capability, suggesting that the intestinal microflora of human is stable and resistant to change.
The study was designed with two groups of individuals, one utilizing a high-soy diet while the other a low-soy diet. Each group is made up of a random selection of 38 individuals from a pool of staff and students in King’s College, London. They were aged 18 to 45 years old and were non-smokers. The study is concluded after a 10-week period; the concentration of metabolites (Genistein, Daidzein, Glycetein, Equol, O-DMA) in each subject’s plasma, urine, and fecal excretion were measured daily. Concentrations of isoflavone and their metabolites in plasma, urine, and feces were significantly higher in the high-soy diet group than the low-soy diet group. Equol was detected in 34% of the individuals in both groups which is in correlation with previous studies in which about 35% of the Western population are good equol producers. According to the results, there is little variation in isoflavone metabolism within an individual due to the uptake of high-soy or low-soy diet. This shows that chronic soy consumption does not induce significant changes in isoflavone metabolism in the gut. Image: From Wikipedia – isoflavone.
Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans1,2,3
Author: Marianne C Walsh, Lorraine Brennan, J Paul G Malthouse and Michael J Gbney. American Journal of Clinical Nutrition, Vol. 84, No. 3, 531-539, September 2006.

### The Effect of Acute Dietary Standardization on the Urinary, Plasma, and Salivary Metabolomic Profiles of Healthy Humans Using H Nuclear Magnetic Resonance Spectroscopy Followed by Multivariate Data Analysis.

To analyze the effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans using H nuclear magnetic resonance spectroscopy followed by multivariate data analysis.

#### New Terms
##### Metabolomics

    A field which detects and quantifies the lower molecular weight molecules, known as metabolites produced by living cells under different conditions i.e nutrient diet. (http://www.bmrb.wisc.edu/metabolomics/)

##### Nutritional Metabolomics

    The global analysis of metabolites, which provide nutrition research with an alternative to the traditional single biomarker approaches to assess health and disease.(http://www.ajcn.org/cgi/content/full/82/3/497)

##### Metabolic profiles

    Metabolic composition in a given system or which varies under different conditions like nutrition.

##### Multivariable data analysis

    A data analysis tool used to analyze data sets consisting of a large number of variables. It reduces this multidimensional data into principal components that can be viewed by using low-dimensional plots. (http://www.ajcn.org/cgi/content/full/84/3/531)

##### Biofluids

    A biological fluid. Biofluids can be excreted (such as urine or sweat), secreted (such as breast milk or bile), obtained with a needle (such as blood), or develop as a result of a pathological process. (http://www.medterms.com/script/main/art.asp?articlekey=38690)

#### Summary

The article was about the effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans. The research in the following paper was done to assimilate metabolomics with nutritional science and increase the present research and clinical practices by giving a deeper approach into the relations between diverse metabolite arrays. The metabolomics were achieved by smallest data capture from biofluids or tissue analysis through the use of technologies such as NMR, pattern recognition statistics.
The biological samples urine, saliva and plasma were collected at 4 laboratory visits. The first two visits the subjects were instructed to carry out their daily schedule and record their diet and physical activity, third visit is just the repeat of the 2 visit. These three visits were intended to appraise intra-individual variation in metabolic profiles. The 4 visit the volunteers were provided with a full range of foods to form a standard diet (i.e fish) to appraised inter-individual variation.
The Principal components analysis results clearly indicated that visit 4 a reduction in inter-individual variation was observed in urea. The CV of the variables from the information rich region of 1 H NMR suggests that the variation suggested that the variation in plasma was not reduced after the standard diet. The principal component analysis score plot accounted 59% variation in the saliva sample. But overall intra-individual variation was lower than inter-individual variation. Average CV of the variables from the information rich region of 1 H NMR suggests that the variation in saliva was not reduced after using the standard diet.
The study appraised the extent of variation in salivary metabolic profiles and established a relatively high level of both inter-and intra-individual variation. The extent of this variation was not reduced even the standardized dietary intake. Even though gut microflora has a relationship with metabolic process it doesn’t influence the variation in metabolic profiles. Hence the paper also discusses that the result of reduced change in the variation in urinary metabolic profiles after standard has no relation with the gut microflora.

#### Relevance to course

This article is applicable to the course because it deals with metabolites and metabolomics which we have been discussing in the class quite a bit. The article talked about the variation in metabolites after high nutrient meal which is very important for the study of nutrient metabolomics. It also important due to the fact, that metabolites variation can alter the actions of various pathways.

#### Relevance to the articles

The following article talks about metabolomics and metabolites which is also the main focus in all the other articles. And also to the fact that how large bowel metabolites vary with high diet. Hence all of the articles talk about nutrient metabolomics.
Absorption and Metabolism of Isoflavones

### The Mechanism of Absorption and Metabolism of Isoflavones and its Similarity in Chemical Structure to Estradiol

To explain the mechanism of absorption and metabolism of isoflavones, its similarity in chemical structure to estradiol (main female hormone).

#### New Terms
##### Pharmacokinetics

    It is a branch of pharmacology dedicated to resolve the fate of substances that are administered externally to a living organism. (http://en.wikipedia.org/wiki/Pharmacokinetics)

##### Bioavailability

    Bioavailability refers to the extent to and rate at which the active moiety (metabolite) enters systemic circulation, thereby accessing the site of action. (http://en.wikipedia.org/wiki/Bioavailability)

##### Biotransformation

    Biotransformation is the process whereby a substance is changed from one chemical to another (transformed) by a chemical reaction within the body. Metabolism or metabolic transformations are terms frequently used for the biotransformation process. (http://en.wikipedia.org/wiki/Biotransformation)

##### Isoflavones

    They are secondary vegetable substances, which act as estrogens in the body and also have protective function. It also helps in regulation of homeostasis in a living system (human). Bacteria in the intestinal flora transform Isoflavones obtained from soybeans one of the main sources, during digestion. (http://www.isoflavones.info/)

##### Phytoestrogens

    Sometimes called "dietary estrogens", are diverse groups of naturally occurring non-steroidal plant compounds that, because of their structural similarity with estradiol, have the ability to cause estrogenic or antiestrogenic effects. Isoflavones are phyoestrogens. (http://en.wikipedia.org/wiki/Phytoestrogens)

#### Summary

The website talks about the absorption and metabolism of Isoflavones. Isoflavones are a group of substances that are obtained from a non-nutrient food like soybeans. The website also emphasizes on chemical structure of Isoflavones and its relevance with female hormone estradiol, and how one can superimpose with each other so they cannot be distinguishable. It also talks about influence of this chemical structure property to help the Isoflavones fit beautifully into the pocket presenting the binding domain of the estrogen receptor. The website also indicates that chemical property of Isoflavones is very important as it influences the biological activity, the bioavailability, and therefore the physiological effects of these dietary constituents. It emphasizes that previous researches made it clear that intestinal microflora play a key role in the metabolism and bioavailability of phytoesterogens.
The website talks a lot about the facts that after injection, soybean Isoflavones are hydrolyzed by intestinal glucosidases, which releases the aglycones, daidzein, genistein and glycitein and can be further metabolized to form specific metabolites, including equol. It also tells that high carbohydrate milieu, causes increased intestinal fermentation, resulting in more extensive biotransformation of phytoesterogen, with increase of equol, a mammalian isoflavone metabolite.
The website also emphasizes on how endogenous estrogens, Isoflavones go through an enterohepatic circulation; they are secreted in bile and uses references from researches done in rats and pharmacokinetic studies to indicate that absorption takes place along the entire length of the intestine. Conjugation of isoflavones to glucuronic acid, a reaction catalyzed by one of the UDP-glucuronyltransferase isozymes, occurs on first-pass. It also talks about how estradiol, isoflavones are found in plasma mostly in the form of glucuronide conjugates.
The website talks a lot about how phytoestrogens are less avidly bound to serum proteins; equol for example shows 10-fold less affinity for serum proteins that estradiol, and therefore a greater proportion will be available to occupy the estrogen receptor, which hypothetically may bolster the effectiveness of isoflavones. Overall, when soy is consumed on a regular basis, levels far exceed normal plasma estradiol concentrations, which in men and women generally range between 40-80 pg/mL.

#### Relevance to course

This article is applicable to the course because it deals with metabolites and metabolomics which we have been discussing in the class quite a bit. The website also talks about the how non-nutrient sources change the bioavailability and metabolites which can change the various cell cylce’s we talked in the class. It also important due to the fact, that isoflavones can mimic the female hormone estradiol which can alter the actions of various metabolites.

#### Relevance to the articles

The following article talks about metabolomics and metabolites which is also the main focus in all the other articles. Hence all of the articles talk about nutrient metabolomics.
Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

### Inhibition by White Tea of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine-Induced Colonic Aberrant Crypts in the F344 Rat

To determine the effectiveness of white tea in its inhibition of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine-Induced Colonic Aberrant Crypts in F344 Rats

#### New terms
##### Aberrant

    Abnormal(http://www.merriam-webster.com/dictionary/aberrant)

##### Catechins

    A compound that is found in tea; it possesses antioxidant properties.(http://en.wikipedia.org/wiki/Catechins)

##### Densitometry

    A measurement determined by exposure to light on light-sensitive materials; it provides a quantitive measurement of optical density.(http://en.wikipedia.org/wiki/Densitometry)

##### Isoforms

    Proteins that share a similar function/sequence while being produced by different genes.(http://www.biology-online.org/dictionary/Isoforms)

##### Preneoplastic

    Pre-tumor state.(http://medical-dictionary.thefreedictionary.com/preneoplastic)

#### Summary

In recent years the consumption and popularity of tea has increased, partially due to recent discoveries linking natural ingredients in tea with health benefits. Some health benefits include anti-carcinogenic properties, which is the focus of this article. Green and Black teas, being the more commonly consumed/processed forms of tea, have been shown to have similar properties. This study shows that white tea offer a higher level of health benefits in terms of protection than that of its green and black brethren.
White tea is the least processed form of tea and is shown to be an inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts. The study, conducted over eight weeks, involved the use of 344 male Fischer rats which divided into three groups. These three groups were given solely drinking water or PhIP and their carcinogen metabolite profiles were determined. The study showed that white tea is an inhibitor of PhIP-induced ACF in rats and white tea provided a higher level of protection than its green and black counterparts.
When broken down, white tea is comprised of nine major parts; these nine major parts when combined produced a weak inhibiting effect on heterocyclic amines. The ineffectiveness shows that all parts of the white tea are crucial to an effective inhibition of heterocyclic amines. In human lung cancer cells, the minor constituents and major constituents of white tea have been shown to have a synergistic effect.
The health benefits of tea is primarily due to the presence of high levels of catechins and polyphenols. They operate on the inhibition of activated metabolites of carcinogens and mutagens as well as other important metabolic pathways. The study discussed in this article built on the discovery of the antimutagenic effects of white tea and showed that white tea can inhibit PhIP-induced ACF in rats. It is believed that the inhibition caused by white tea is due to changes in carcinogen-metabolizing enzymes. Future studies can help further the understanding behind the metabolism of tea.

#### Relevance to course

This article is relevant to the course because it focuses on how constituents of white tea, such as catechins and polyphenols, can inhibit heterocyclic amines resulting in an anti-carcinogenic effect. The article discusses how the metabolic pathways may be disrupted by changes in carcinogen-metabolizing enzymes.

#### Relevance to other articles

This article is relevant to the other articles as it discusses how ingesting of certain foods can alter the body’s metabolism. These articles focus on potential health benefits and unlocking the specific pathway by which these benefits occur.

### Probiotic Bacteria Influence the Composition and Function of the Intestinal Microbiota

To review the effects of probiotic bacteria on the composition and function of the intestinal microbiota.

#### New Terms
##### Allochthonous

    Not native; found in a place other than where they were formed. (http://www.thefreedictionary.com/allochthonous)

##### Autochthonous

    Native; found in a place where they were formed. (http://www.merriam-webster.com/dictionary/autochthonous)

##### Commensals

    A symbiotic relationship between two species, where species A is benefiting and species B is unaffected (http://medical-dictionary.thefreedictionary.com/commensals)

##### Microbiota

    Normal microorganisms that are regularly found to inhabit a body part or organ, typically do not cause disease. (http://medical-dictionary.thefreedictionary.com/microbiota)

##### Probiotic

    Microbiota whose dietary supplements are considered healthy for their host. (http://en.wikipedia.org/wiki/Probiotic)

#### Summary

This article reviews the role of probiotic bacteria of other microbiota in the intestines. Probiotic bacteria have been shown to provide health benefits for the host by regulating the elements of the microbiota in the body. The body contains microorganisms called normal flora that do not normally cause disease to the body, there are over 1000 phylotypes in the intestines.
Probiotic bacteria affect the intestinal microbiota through competition to have levels of microorganisms that improve health. Through research on these probiotics, regulation of the interactions of microbiotia, probiotic bacteria and diet, human health can be further optimized. Currently a multitude of vaccines and treatments have been developed after substantial research on microorganisms in the body.
Probiotic bacteria were previously known as fermentative bacteria and recent studies involving probiotic bacteria and microbiota have been conducted using culture-independent methods. Like microbiota, probiotics are non-harmful and beneficial in adequate amounts. These probiotics were and are still used to preserve foods, they are typically members of the genera Lactobacillus or Bifidobacterium.
The article discusses prebiotic compounds which are indigestible foods that can benefit the host by stimulating growth of bacteria in the intestines. Prebiotics can be found in fruits, vegetables and cereals. It has been shown that increased barley in rodents’ diets will lead to an increase in butyrate, which is an important energy source and has anti-carcinogenic effects.
The use of probiotics and prebiotics is not new; they have practical application to production animals, such as the use of bacteria to increase weight gain in broiler chickens. Some human studies include the use of probiotics to reduce diarrhea induced by Clostridium difficile. Currently there is a market for discovering a probiotic bacteria that can treat irritable bowel syndrome (IBS). The key to this is to determine the effect of diet, host factors, and microbiota on each other.

#### Relevance to Course

This article is relevant to the course because it discusses the role of probiotic bacteria and their ability to help facilitate metabolism in the body. Probiotic bacteria can have a beneficial health role by altering metabolism of the large intestine. In addition, short chain fatty acids (SCFAs), such as butyrate play a role in providing energy under the fatty acid metabolism pathway.

#### Relevance to Other Articles

This article is relevant to the other articles because it discusses metabolism within the intestines. Once again, there is focus on the health implications of discovering the optimal probiotic bacteria levels in the body and how they interact with host factors and microbiota.

### Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

To provide a better understanding of the role of soluble fibers such as Guar gum in the regulation of cholesterol metabolism.(http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2605338&tool=pmcentrez#b8-vhrm-4-1023)

#### New Terms
##### Atherogenic

    The process by which atherogenesis (formation of fatty lipids on the arterial walls) occurs.(http://medical-dictionary.thefreedictionary.com/atherogenic)

##### Enterohepatic

    In regards to the intestines and liver.(http://www.merriam-webster.com/medical/enterohepatic)

##### Emulsification

    The first step in preparing fat globules for chemical digestion; breakdown of larger particles into smaller particles.(http://medical-dictionary.thefreedictionary.com/emulsification)

##### Ileostomy

    A surgical opening of the ileum to allow for feces to be removed.(http://medical-dictionary.thefreedictionary.com/Ileostomy)

##### Polymorphisms

    The ability to vary in form during different stages of development.(http://medical-dictionary.thefreedictionary.com/Polymorphisms)

#### Summary

The article is brings to light the importance of soluble fibers in our diets and their role in the regulation of cholesterol metabolism. Soluble fibers, such as guar gum, have the ability to lower blood cholesterol levels as shown in countless animal models and human clinical studies. Dietary fiber has a protective role against coronary heart disease and other cholesterol-related diseases, such as atherosclerosis.
Although the role of dietary fiber (dietary fiber hypothesis) in combating cardiovascular disease has been accepted early in the 1970s, the definition of dietary fiber was a source of contention for years to come. Dietary fiber was defined by Trowell in 1972 as ‘the skeletal remains of plant cells that are resistant to hydrolysis of the enzymes of man’. In 2001, the American Association of Cereal Chemists (2001) proposed a more detailed definition: ‘dietary fiber is the edible parts of plants or analogous carbohydrates that are resistant to digestion and absorption in the human small intestine with complete or partial fermentation in the large intestine. Finally in 2007, the Joint FAO/WHO Expert Consultation on Carbohydrates in Human Nutrition proposed that dietary fiber should be defined as ‘intrinsic plant cell wall polysaccharides’. Regardless of the definition, it is agreed by health authorities worldwide that increased fiber consumption is needed.
Soluble fibers are different from insoluble fibers in that they are highly viscous and ferment into short-chain fatty acids in the large bowel, the viscosity interferes with key physiological events that occur during the cholesterol absorptive process. They act primarily in the intestine to promote secondary responses in the liver; soluble fiber reduces dietary fat and cholesterol uptake in the intestine. It is interesting to note that the greatest cholesterol reduction with dietary fiber consumption occurs when partnered with a high-cholesterol diet.
The effect of dietary fiber on cholesterol metabolism is known to help absorb cholesterol and result in fecal sterol and bile acid loss. With the advances in technology and science, we can now attempt to maximize the role of dietary fiber to each individual by determining the role of genetic variability between individuals. If this is achieved, fiber-cocktails can be tailored to target specific metabolic pathways to result in maximal cholesterol reductions.

#### Relevance to Course

The article is relevant to the course Biochemistry: Metabolism because the article discusses the role of dietary fibers (soluble fibers) in metabolic pathways. Soluble fibers which are viscous are known to interfere with the enterohepatic circulation of cholesterol, which helps to reduce cholesterol.

#### Relevance to Other Articles

The article is relevant to other articles as this article discusses the role of dietary fibers in the intestines. Dietary fiber is known to readily ferment into short-chain fatty acids in the large bowel.

### Absorption and metabolism of octanoate by the rat colon in vivo: concentration dependency and influence of alternative fuels

To show that the colon can absorb and metabolize octanoate, a medium-chain fatty acid (MCFA), which is dependent on substrate concentration and alternative luminal fuels. (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1773271&tool=pmcentrez)

#### New Terms
##### Cannula

    A flexible tube that, when inserted into the body, is used to drain fluids from or provide medication to the body. (http://www.thefreedictionary.com/cannula)

##### Luminal

    Pertains to the internal cavity of a tubular organ. (http://www.merriam-webster.com/dictionary/luminal)

##### Mesenteric

    Pertains to the mesentery which is a double layer of peritoneum which helps suspend the intestine. (http://medical-dictionary.thefreedictionary.com/mesenteric)

##### Perfusate

    A fluid that is used to pass through a membrane or material. (http://www.biology-online.org/dictionary/Perfusate)

##### Scintillation

    A radioactive emission which can be detected by a scintillation counter. (http://www.merriam-webster.com/dictionary/scintillation%20counter)

#### Summary

The article discusses the colon’s ability to use medium chain fatty acids (MCFAs) to fulfill their basic energy requirement. It has been shown that short chain fatty acids (SCFAs), such as butyrate, are the main source of fuel for the colonic mucosa. This study sets out to determine other sources of fatty acids for both research and clinical use; colonic absorption of MCFAs is likely a major contributing factor to the success of oral MCT therapy in small bowel compromised patients.
Although SCFAs are readily absorbed, MCFAs are capable of being absorbed by the animal and human colon. In comparison to SCFAs, MCFAs provide the highest colonic absorption of substrate carbon and fulfill the energy needs of colonic epithelial cells. The study proves this through the use of an in vivo rat model; octanoate and decanoate were oxidized to carbon dioxide as efficiently as butyrate. The in vivo model is necessary to ascertain the effects of MCFAs on fatty acid metabolism as in vitro techniques are unreliable. The MCFAs showed an increase in total carbon being transported in comparison to SCFAs. MCFAs could provide 20% of the basal metabolic needs which can help individuals with a defective small bowel.
The study involved fifteen rats which were separated into five groups. The rats were operated on to provide access to a segment of proximal colon and the right colic vein. The area was perfused with MCFAs and the blood draining from this segment was analyzed for metabolites. The data showed significant absorption of octanoate (MCFA) by the colon which was dependent on carbon dioxide and ketone bodies.
There is potential for clinical use of this research for individuals with compromised small bowel function. Colonic absorption of MCFAs is a contributing factor to oral MCT therapy in small bowel compromised patients.

#### Relevance to course

The article is relevant to the course Biochemistry: Metabolism because the article discusses the ability of the large intestine to absorb small chain fatty acids as well as medium chain fatty acids in the fatty acid metabolism pathway. SCFAs and MCFAs fuel the colonic mucosa and helps it maintain its structure and function.

#### Relevance to the articles

The article is relevant to other articles as this article discusses the role of SCFAs and MCFAs in the large intestine. The article discusses the clinical use of large bowel metabolites for individuals.

### Insights into the roles of Gut Microbes in Obesity

To determine the roles of gut microbes and their relationship to obesity.

#### New Terms
##### Transcriptomics

    The study of the transcriptome, the complete set of RNA transcripts produced by the genome at any one time.( http://www.medterms.com/script/main/art.asp?articlekey=23518)

##### Acetogenesis

    Acetogenesis is a process through which acetate is produced by anaerobic bacteria from a variety of energy (for example, hydrogen) and carbon (for example, carbon dioxide) sources. (http://en.wikipedia.org/wiki/Acetogenesis)

##### Adipokine

    The adipokines or adipocytokines are cytokines (cell-to-cell signalling proteins) secreted by adipose tissue.( http://en.wikipedia.org/wiki/Adipokine)

##### Bacteroidetes

    An abundant organism in the feces of warm-blooded animals including human.(http://en.wikipedia.org/wiki/Bacteroidetes)

##### Firmicutes

    a taxonomic phylum, within kingdom Bacteria - very many bacteria, mostly gram-positive(http://en.wiktionary.org/wiki/Firmicutes)

#### Summary

Obesity is one of the major health concerns in United States of America as chances of having other chronic diseases increases because of obesity. One of the main reasons behind obesity is disproportional balance between the amount of energy that we consume and the amount of energy we expel. Gut microbes play a major role in terms of storing energy that we get from consuming diet which enhances the gain of weight. Out of Gut microbial groups; Bacteroidetes and Firmicutes constitute the majority in that group and based on the bacteroidetes to firmicutes ratio; weight regulation can be analyzed.
The gut microbiota are also involved in energy metabolism and immune system. These bacteria have hydrolyses and transporters that digest nutrients, polysaccharides that serve as main sources of energy for bacteria that dominate large intestine and have an advantage compared to transient bacteria.
Firmicutes are also butyrate producing bacteria which signifies higher gut metabolic activity leading to overweight. Butyrate can also be advantageous to obese prone bodies as it helps in anti inflammatory functions too. It also affects energy balance by adjusting gene expression of metabolic functions. Gut microbiota also influence innate and adaptive immunity. When antibiotic administration causes inhibition of gut microbiota which results in low grade inflammation; type-2 diabetes, etc.
In short, gut microbes are a unique factor involved in body weight gain. Also due to different relations microbiota structure and different phenotype, microbes affect body weight differently.

#### Relevance to Class

Biochem metabolism has taught us about many metabolic processes that have helped understand the reasons behind gut microbiota influencing obesity. Also understanding the energy metabolism was easier because of the metabolism course.

#### Relevance to Other Articles

It enlightens our knowledge on large bowel metabolites and talks about how metabolic activities and talks about how metabolic activities can affect our body weight and we learn about these metabolic activities in large intestine in our next article.

### Protein Degradation in the Large Intestine Relevance to Colorectal Cancer

To discuss how protein degradation in the large intestine relates to colorectal cancer.

#### New Terms
##### Aeitology

    The branch of medical science that studies the causes of diseases and the factors underlying their spread.( http://www.thefreedictionary.com/aetiology)

##### Uterosigmoidoscopy

    Ureterosigmoidoscopy is a surgical procedure that treats urinary incontinence by joining the ureters to the lower colon, thereby allowing urine to evacuate through the rectum. (http://www.enotes.com/surgery-encyclopedia/ureterosigmoidoscopy)

##### Genetoxicity

    damaging to genetic material (http://www.merriam-webster.com/medical/genotoxic)

##### Colorectal

    Of or pertaining to the colon, rectum, or both. (http://en.wiktionary.org/wiki/colorectal)

##### Microflora

    Microscopic plant life, especially the bacterial colonies found in the gut of normal, healthy animals and humans. (http://en.wiktionary.org/wiki/microflora)

#### Summary

In today’s era, cancer is still one of the most deadly and incurable diseases present in many western countries out of which colorectal cancer is the second most common form. Diet does affect colorectal cancer directly or indirectly. Evidence shows that people have more meat and fat in their diet are more susceptible to this kind of cancer. The reason behind that is because of the enhanced protein metabolism due to the high intake of protein in meat and when this protein degrades; ammonia, phenol and enol are the toxic side products which have gut mucosal effects. A huge diversity of bacteria enters the large intestine. Gut microflora is one of them and their role is to extract energy from non-digestible dietary substrates like carbohydrate and protein. Short chain fatty acids are one of the main products of metabolism and also serve as an energy source for colonocytes. Some of the products of carbohydrate metabolism have had beneficial effects where as products of colonic protein degradation might be toxic. One of which is ammonia and the main source is amino acid deamination and its effects involve tumor promotion. Tumor promotions results in affecting DNA synthesis and reduce lifespan of cells. Another product of colon protein degradation is phenolic compound which are formed due to bacterial degradation of phenylalanine, tyrosine and tryptophan which have sometimes been detected in proximal regions. The relation between phenol production and cancer though still remains clear. In short, it is probable that toxic products from colonic protein metabolism result into increase in genetoxicity.

#### Relevance to the course

It is relevant to the class course as this article talks about metabolism of protein and how the byproducts can lead to tumor and ultimately cancer. Therefore it helps us provide examples of the metabolism mechanisms that we learnt in the course

#### Relevance to other articles

This article talks about protein metabolism which we even learnt in other article and they both directly affect the well being of an individual as that article talked about how it affects obesity and this article refers to affect colorectal cancer.

### The Influences of external bacterial on the relationship of intestinal microbiota and human large-bowel metabolism.

To discuss the influences of external bacteria on the intestinal microbiota living in human large-bowels and their role in metabolism.

#### New Terms
##### Microbiome

    the totality of all the microbiota, the genomic elements, and environmental influences on a defined system. (http://en.wikipedia.org/wiki/Microbiome)

##### Phylogenetic Analysis

    an analysis performed to study the evolutionary relationship between various groups of organisms. (http://en.wikipedia.org/wiki/Phylogenetic)

##### Metagenomic

    The study of collective genomes in a given system. (http://en.wikipedia.org/wiki/Metagenomics)

##### Probiotic

    Substances that are ingested to promote healthy flora in the digestive system. (http://en.wikipedia.org/wiki/Probiotics)

##### Microbial Biofilms

    an aggregate of bacteria on an adherent matrix. (http://en.wikipedia.org/wiki/Biofilms)

#### Summary

This article discusses the potential of applying systems biology in Human Colon Microbiomes. The symbiotic relationship between intestinal microbiota and human metabolism is very complex, however to map out the different pathways and environmental influences of this relationship can be an extremely powerful tool. This can bring about the use of probiotics and manipulation of large bowel metabolism for therapeutic purposes. Although age, medical history, diet, and culture can determine the type of microbiota colonizing the gut, external microbiota play a special role. Phylogenetic Analysis shows the complexity and diversity among the intestinal microbiota. However, only about 20% of these bacteria have been cultivated and studied. Given the technological advancements over the past few years, there is a need to catalog the diverse microbiota in the intestinal lumen. This will give us a better understanding of the molecular interactions between the newly arrived and residential microbiota, allowing us for a clear understanding of the human large-bowel metabolism.
There are certain important aspects about the interactions of bacterial colonies that should be monitored in particular. Differing microbiota undergoing different metabolic processes give rise to different products. The diverse groups of microbiota allow for another organism to further processes the product of another microbiota species. This mechanism of favorable processing allows specific survival patterns of the next microbiota, influencing the level of specific metabolites in the colon. Through the use of biotechnology, such as metagenomics, to catalog the totality of the microbiome of the colon will allow for the proper metabolic mapping. This will give rise to the use of probiotics to manipulate the outcome or production of certain metabolites and allow for restoration of pathology and promote good health.

#### Relevance to course

This article is applicable to the course because it deals with the diverse pathways of metabolism. The article talks about the different processing pathways and interconnecting pathways that can lead to a favorable growth in the next organism. This is similar to molecular metabolic pathways where enzymes and substrates form products for the next enzyme to work on. We have already had success with molecular pathways, and applying the same systematic approach to catalog and map the microbiota at an organism level has great potential.

#### Relevance to the articles

This article is essential to the other articles, because without microbiota, large bowel metabolism would not readily occur. These microbiomes in the large bowel are critical for the formation of essential metabolites that the human metabolic pathway cannot form.

### Microbiota Conversion of Polycyclic Aromatic Compounds to Estrogenic Metabolites

To review microbiota conversion of polycyclic aromatic compounds to form estrogenic metabolites.

#### New Terms
##### Polycyclic Aromatic Hydrocarbons

    chemical compounds that consist of aromatic rings fused together. (http://en.wikipedia.org/wiki/Polycyclic_aromatic_hydrocarbons)

##### Aryl Hydrocarbon Receptor

    a receptor that causes an transduction cascade that activates several transcription factors. (http://en.wikipedia.org/wiki/Aryl_Hydrocarbon_Receptor)

##### SHIME (Simulator of Human Intestinal Microbial Ecosystem)

    the experimental set-up used to simulate the conditions from the stomach to the colon. (http://labmet.ugent.be/easycms/staff/Dr._ir._Sam_Possemiers)

##### LC-MS Analysis (Liquid Chromatography/Mass Spectrometry)

    an analytic technique to identify chemical structures, determine mixtures, and quantify findings through the use of a mass spectrometer. (http://www.answers.com/topic/mass-spectrometry)

##### Estrogenicity

    relation to or cause of estrogen (http://wordnet.princeton.edu/perl/webwn)

##### HPLC (High Performance Liquid Chromatography)

    used to separate compounds in a solution. (http://en.wikipedia.org/wiki/High_Performance_Liquid_Chromatography)

##### Aromaticity

    The property of organic compounds which have at least one conjugated ring of alternate single bond and double bonds, and exhibit extreme stability (http://en.wiktionary.org/wiki/aromaticity)

#### Summary

This article explored the effects of large-bowel microbiota on the metabolic transformation of Polycyclic Aromatic Hydrocarbons (PAH) to estrogen metabolites. In past experiments, there have been documented cases about the human transformation enzymes that were involved in PAH metabolism. However, the effects of microbiota within the digestive tract have not been explored. This study examined the effects of large-bowel microbiota and compared it to the stomach and small intestines.
Using a Simulator of Human Intestinal Microbial Ecosystem (SHIME), they were able to model the environments of the human digestive tract. The SHIME experiment consists of 5 well-monitored vessels that contains the exact contents in a normal human individual. Each vessel has a pH monitor and appropriate concentration of enzymes and reagents necessary for normal digestion. With the capability of extracting samples at any level of digestion, they used an estrogen bio-assay to quantify the levels of estrogen metabolites in each stage of digestion. The results showed that estrogenic metabolites were ten-fold greater in the colon compared to the other vessels. Furthermore, when they compared the levels of colon microbiota to estrogenic metabolites, they found that estrogenic metabolites increased with the population of colon microbiota.
To finalize the support of their research, they performed a Liquid Chromatography and Mass Spectrometry to confirm their conclusions. The LC-MS study specifically determined the molecular interactions that occurred during each stage of transformation. Past articles suggested that the colon microbiota hydroxylated the PAH using an oxidation reaction. However, this study demonstrates that this is unlikely and further investigation is needed. By showing that PAH ingestion creates estrogenic metabolites, a new pathology or perhaps therapeutic target has been identified. This discovery shows both the potential of cataloging and mapping the metabolic maps through the use of a systematic approach.

#### Relevance to the course

This article demonstrates the complex pathways of the human metabolism. The relationship between the bacteria and the human gut further extend metabolic pathways of humans into bacterial metabolism as well. In whole, we can see how intertwined and how similar the molecular interactions are within all organisms.

#### Relevance to Other Articles

This article gives a concrete example of the complex relationships and molecular interactions between the microbiota and human metabolism. It not only provides evidence for the involvement of colon bacteria on large bowel metabolism, but it also depicts an effective way to quantify and support the conclusions.

## Websites for future review as Metabolism class assignments

Investigation of the role of vitamin A on nerve cell development in the bowel http://hopecenter.wusm.wustl.edu/news/latest/Pages/RobertHeuckerothinvestigatestheroleofVitaminAonnervecelldevelopmentinthebowel.aspx
Bile acids metabolism http://www.meddean.luc.edu/lumen/meded/orfpath/bileacids.htm
Drug absorption and metabolism in the G.I. tract (powerpoint presentation) http://www.eohsi.rutgers.edu/internal/classes/introtopharmacology/GItractADME112907.ppt
Gastro-intestinal disturbances (powerpoint presentation) http://healthscience.cypresscollege.edu/~courses/notes/196notes/GI%20new%201962002.ppt