Introduction
The human large intestines have a lot of microbial flora, which relies on the human body as a food reserve for their growth and development. This microbial community has metabolic activities that are independent of the host. Microbial activities in the human large intestine, particularly the colon, have different effects to the human health. The metabolites that are produced by the action of these microbial communities in the colon are determined by the type of food substituent being metabolized. Similarly, the type of diet an individual usually takes determines the type of colonic microbiota (Conlon and Bird, 2014, p.28). This review will address the colonic fermentation of undigested proteins and the health of human beings.
In the colon, undigested proteins are fermented to produce different metabolites which have diverse health impacts. One of the metabolites of fermentation of proteins is aromatic amino acid metabolites (AAA). Phenol, p-cresol and indole are the three major metabolites of aromatic amino acids. The metabolism of the aromatic amino acid is conducted by different bacteria. Some of the major bacteria in the metabolism of the aromatic amino acid include Bacteroides thetaiotaomicron, B. Ovatus and B. fragilis among many others. Micronutrients which reaches the large intestine before digestion affects the composition of the gut microbiota as well as the presence of aromatic metabolites (Louis, Hold and Flint, 2014, p.661). For instance, some metabolites such as SCFA and phenyl are usually produced by metabolism of CHO and proteins in the colon (Sonnenburg and Backhed, 2016, p.56). However, fatty acids and metabolites that have nitrogen are usually produced from the metabolism of protein only. Therefore, large constituents of undigested proteins in the large intestine are usually accompanied by colorectal cancer. Most commonly, animal protein consumption is one of the risk factors for the disease.
Colorectal cancer is also known as the bowel, colon or rectal cancer. As previously stated, colorectal cancer is stimulated when an individual takes animal proteins frequently. The disease is even more significant to old age people and significant among women compared to men. However, it is vital to understand that colorectal cancer as a result of animal proteins usually occurs when people consume processed meat. The disease usually develops within polyps which are located in the bowel wall (Feng et al., 2015, p.6528). The development of the disease in the polyps is accelerated when an individual consumes red as well as processed meat.
Aromatic gut metabolites may also have a positive health impact. It is scientifically proven that aromatic gut metabolites in the systemic circulation have a significant effect on the vascular health of a person. It is clear that diet gotten from aromatic compounds are xenobiotics. These xenobiotics are usually conjugated in the liver where they are released to the intestine through the bile. Once in the large intestine, the xenobiotics' conjugates are cleaved by a bacteria called v-glucuronidases. The cleaving of these conjugate is accompanied by the release of an aromatic moiety which is absorbed back to the liver. This process is called enterohepatic circulation which has a positive health impact on the human body. However, the v-glucuronidases concentration may have an adverse effect on the colon. It is clear that v-glucuronidases bacteria may form short-chain fatty acids (SCFA). Different fermentation produces are produced depending on the relative synthesis as well as well as the intestinal environmental conditions. On the other hand, acrylate gives a limited distribution where lactase forms the main substrate. The SCFA usually has propionate in a varied amount which links with the number of bacteria in the intestine.
On the hand, butyrate is produced using different compounds and enzymes. Some of the enzymes that are used during the production of butyrate include the butyryl-CoA acetate as well as a CoA-transferase enzyme. Species which use the above enzymes to produce butyrate are commonly the dominant species which forms gut microbiota (Marchesi et al., 2015, p.67). These organisms usually play a vital role in maintaining the homeostatic balance of the human body. This is done by the stabilization of microbial ecosystem through the prevention of accumulation of lactate.
The SCFAs may also have a different impact on the host cells. For instance, butyrate and acetate absorption in the lumen may have different effects on cell metabolism. Butyrate usually forms the main source of energy to the gut epithelial cells. On the other hand, acetate produces a great concentration in the exterior plasma. Butyrate may also have negative effects on the human health. For instance, intracellular butyrate may affect the activity of histone deacetylase. Mostly, the butyrate causes the inhibition in immune cells. The inhibition may have significant effects on gene expression. One of the most significant effects of a hindrance to histone deacetylase activity is the downregulation of pro-inflammatory cytokines.
Recent studies show that butyrate may also have a significant role to play in the differentiation of regulatory T-cells. This differentiation is accompanied with the expression of a transcription factor which aids in controlling intestinal inflammation (Kostic, Xavier and Gevers, 2014, p.1492).it is proposed that butyrate leads to a rise in acetylation of histone in scurfin locus which causes an increased major bacterial fermentation product. Several studies show that interactions between SCFAs and G protein-coupled receptors occur in different cells apart from colonocytes. Some of these cells include macrophages as well as T cells. These processes usually lead to an increase in colonic regulatory T cells as well as the production of substances that hinder inflammation in the lumen.
The anti-inflammatory effect of SCFAs is not only significant affecting the host cells but also in maintaining equilibrium in the microbiota. An interesting hypothesis states that the anti-inflammatory impact of high levels of butyrate usually hinders the immune response to the gut microbiota (Richards et al., 2016, p.82). Similarly, a low butyrate level causes an anti-inflammatory state which leads to the alteration of the gut microbiota. This is done through the process of suppressing potential pathogens and restoring butyrate-producing species.
On the other hand, the gut-liver axis, dietary amines as well as methylamines' pathway forms significant aspects in protein fermentation in the colon. Given the exposure of the liver to various processes in the large intestines as well as catabolites of protein fermentation, an individual health may be affected differently depending on his/her protein consumption (Brown et al., 2016, p.11). For instance, various studies have shown that gut microbiota is involved directly in obesity development among people. This condition is independent of non-alcoholic fatty liver diseases. Similarly, the process is independent of body glucose as well as lipid breakdown. Experiments done on mice that have hepatic macrovesicular steatosis shows that they possess a high concentration of such constituents as isobutyrate and isovalerate. Similarly, these mice have a high concentration of branched-chain amino acids. In addition, the experiment of HMS mice shows that they possess high fasting glycaemia as well as mechanisms such as insulin resistance index. Scrutinizing these results, it is clear that the gut microbiota has an environmental factor that drives the initiation and development of non-alcoholic fatty liver disease (NAFLD) (Shreiner, Kao and Young, 2015, p.69). In general, the intestinal microbiota may influence the gut-liver axis as well as the occurrence of NAFLD among animals. Moreover, the microbiota may also lead to other diseases by utilizing dietary methylamines.
Trimethylamine N-oxide (TMAO) is a substance that is produced from dietary methylamines. Together with cardiovascular disease, they have been extended include l-carnitine. L-carnitine is a substance that is usually found in red meat. The suppression of microbiota in humans using induced antibiotics have significantly affected the presence of TMAO. In the case described above, the induced antibiotics may cause the absence of TMAO in plasma cells as well as urine. Moreover, human beings who consume all forms of food have a higher circulation of TMAO compared to their peers who consume vegetables only. Similarly, individuals who consume vegetables only have a higher concentration of carnitine compared to those who are omnivorous. This shows that the human colon depends on the type of diet an individual consumes regularly. High carnitine levels are detrimental to the human body. For instance, excess carnitine in the human blood plasma is usually accompanied with different diseases. One of the major diseases which is associated with high carnitine levels is cardiovascular disease as previously stated (Zhang et al., 2015, p.7501). However, the disease is common among people who have also a high concentration of TMAO. Trimethylamine N-oxide here plays the role of inducing atherosclerosis by promoting the accumulation of cholesterol through the rise in cell surface expression among many other processes. Similarly, TMAO promotes the repression of reverse cholesterol transport an aspect which also plays a vital part in causing cardiovascular diseases.
Conclusion
In conclusion, microbial mammalian co-metabolism is affecting human health in many different ways. In this review, recent findings in studies regarding SCFAs, AAA as well as methylamine metabolism have been discussed in relation to their impact on human health. Moreover, the consequences of these metabolisms regarding human health and diseases have been addressed. Basically, colonic fermentation of undigested proteins has both negative and positive impacts on an individual's health. Continued studies in the field of food processing on human health will give further insights to personalized nutrition as well as health issues in the future. Similarly, future directions regarding treatment of possible diseases brought about by colonic fermentation of undigested proteins will be available based on the refinement of metagenomics and metabolomics.
Reference List
Brown, D.G., Rao, S., Weir, T.L., O'Malia, J., Bazan, M., Brown, R.J. and Ryan, E.P., 2016. Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer & Metabolism, 4(1), p.11. Retrieved from https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-016-0151-y
Conlon, M.A. and Bird, A.R., 2014. The impact of diet and lifestyle on gut microbiota and human health. Nutrients, 7(1), pp.17-44. Retrieved from https://www.mdpi.com/2072-6643/7/1/17
Feng, Q., Liang, S., Jia, H., Stadlmayr, A., Tang, L., Lan, Z., Zhang, D., Xia, H., Xu, X., Jie, Z. and Su, L., 2015. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nature Communications, 6, p.6528. Retrieved from https://www.nature.com/articles/ncomms7528
Kostic, A.D., Xavier, R.J. and Gevers, D., 2014. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology, 146(6), pp.1489-1499. Retrieved from https://www.sciencedirect.com/science/article/pii/S0016508514002200
Louis, P., Hold, G.L. and Flint, H.J., 2014. The gut microbiota, bacterial metabolites and colorectal cancer. Nature Reviews Microbiology, 12(10), p.661. Retrieved from https://www.nature.com/articles/nrmicro3344
Marchesi, J.R., Adams, D.H., Fava, F., Hermes, G.D., Hirschfield, G.M., Hold, G., Quraishi, M.N., Kinross, J., Smidt,...
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