Wednesday, June 12, 2013

What dirty microbes can do for you?

Most common stereotype of microbes
Microbes are thought to be dirty and the worst enemy in human health that need to be eliminated as soon as possible. Many antibiotic products for sanitizing are readily available to anybody such as Purell, and many antibiotics have been developed and used excessively in the medical field. Excessive use of sanitizing and antibiotic might disrupt the harmonic symbiotic-interaction between human and microbiota on and in human body.
The lack of understanding of microbes might be due to their size which cannot be detected by the naked eyes. However, as the lab techniques and technologies such as gene sequencing have improved, the study of microbes is now much better understood and has changed significantly over the past decades. Indeed, many studies have revealed what the microbes do for us is totally opposite from our traditional thought. Microbes keep us healthy (1) and provide vital functions that are essential for human survival (2). Despite the facts, most people are lack of understanding in microbes and still think of microbes as harmful pathogens such as E. coli. However, this pathogen has been an excellent model organism to help scientists to study in understanding how a cell works, human health consideration, and etc. It was also a model of a beautiful glass art work by the artist Luke Jerram (see Figure 1).

Figure 1. The artist Luke Jerram's glass E.coli work

Skin microbiome: another human organ
The human body is a habitat of microbes coexisting in symbiotic interaction manner. Literally, we are fully covered by microbes including mouth and gastrointestinal tract. The microbes on and in human body are estimated to outnumber human somatic and germ cells by a factor of ten (3). The microbial communities on skin depends on skin characteristics, such as sebaceous gland concentration, moisture content, and temperature, as well as on host genetics and exogenous environmental factors (4). Figure 2 shows a different microbial community found on a different part of human body (5). One of the major pathways to share microbes with the others and environment is the dispersal of microbes which can be achieve by physical contact or proximal exposure. A typical exposure to pathogens can result in illnesses like the well-known flu. All the organisms, including human, constantly interact with other organisms within an environment, and they exchange their microbes with others.

    Figure 2.  Topographical distribution of bacteria on skin sites (5)

Skin plays an important role in providing a barrier from a pathogens and damage. A recent study found that “microbiota extends within the dermis, therefore, enabling physical contact between bacteria and various cells below the basement membrane, direct communication with the host in a tissue which was thought to be sterile previously (6).” In addition, “Staphylococcus epidermidis, a major constituent of the normal microflora on healthy human skin, acts as a barrier against overgrowth of already present opportunistic pathogens (6)” suggesting “the normal human skin microflora protects skin via various modes of action, a conclusion supported by many lines of evidence associating diseases such as acne, atopic dermatitis, psoriasis and rosacea with an imbalance of the microflora even in the absence of classical infection (7).” As see above, microbes, which can be considered another organ, provide another barrier to protect our body against pathogens. Thus, the loss of skin microbes directly affects our health that might threat us in an infection. Overall, microbes enhance immunity and fighting over pathogens in human.

Gut microbiota: associated with metabolism including diabetes and obesity
As seen above, human health is associated with microbes including metabolism. Without microbes, we cannot even digest the most common diet, cellulose, which is sugar synthesized by plants, due to not having an enzyme to cleave β-(1,4) linkage. Figure 3 (9) shows the human gut with examples of good and bad flora. Many researchers have tried to figure out the relationship between the gut microbiota and human health, and recent studies found that diabetes and obesity were correlated with the variation in the microbial communities in our gut.

Figure 3. The human gut with examples of good and bad microbes

In an additional study showed infants who were not breastfed were associated an increased incidence of childhood obesity, type 1 and type 2 diabetes (10). This might result by developing a different microbial community in the gut of formula fed infants compared to breastfed infants. A study with rhesus monkey model showed that formula fed infants had a different gut microbiome from breast-fed infants and higher serum insulin coupled with higher amino acid levels which were higher in breast-fed infants as degradation products (10). This result clearly shows a different microbial community developed in breastfed infants versus formula-feeding infants.Specific amino acids regulate insulin secretion from pancreatic beta cells, so imbalanced amino acid in a cell might lead diabetes. A study has shown that "mitochondrial metabolism is crutial for the coupling of amino acid and glucose recognition to exocytosis of insulin granules (11)," meaning an increased amount of amino acid in a cell might promote glycolysis, glucose uptake. After a meal, uptaking glucose must be occurred, but in fasting state, the liver must make glucose to buffer the blood sugar level. However, high level of amino acid in a human body stimulates glucose uptake literally all the time even in the fasting state.  A diverse microbes in a gut is important in metabolism because each microbe uses a different substrate in our gut as their energy source. Thus, a loss of diverse microbes might lead an accumulation of a substance in our gut, which might lead a metabolism defect.

In addition, Jonathan Eisen (see the video (12)) talked about microbes in and on human. It was originally thought that diabetes was actually caused by the body fighting with pathogen, but as stated in his talk, Type I diabetes is due to miscommunication of microbes in and on human; Some microbes were missing in a diabetic’s microbial community. Microbes help in development immune system, fighting off pathogens, regulation of our metabolisms, and odor. Excessive use of antibiotic particularly in children has shown association of risk in obesity, for autoimmune disease, and for variety of problems, which results in disruption of the microbial community.    

Although there are some pathogens which threat human health, there are more good microbes that protect us from an infection and a metabolism disease like a rotten apple in a barrel. Individuals on the planet are a habitat of microbes, and they are associated in human health including fighting with a pathogen and metabolism. Thus, disruption of the microbial community in and on us affects our health. As a result, we should appreciate what microbes do for us and try not to disturb the microbial community.

(1) Harmon, K. (2009, December) Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear?. Scientificamerican.
(2) MacDougall, R. (2012, June) NIH Human Microbiome Project defines normal bacterial makeup of the body. NIH News.
(3) Turnbaugh, P. J., Ley, R. E, Hamady, M., Fraser-Liggett, C. M., Knight, R., Gordon, J. (2007, October 18) The Human Microbiome Project, Nature 449, 804-810 doi:10.1038/nature06244
(4) Chen, Y. E., Tsao, H. (2013, Mar.12) The skin microbiome: Current perspectives and future challenges, Journal of the American Academy of Dermatology. doi: 10.1016/j.jaad.2013.01.016
 (5) Grice, E. A., Segre, J. A. (2011, April) The Skin microbiome. Nature Reviews Microbiology. 9, p. 248. Doi: 10.1038/nrmicro2537
(6) Nakatsuji, T., Chiang, H., Jiang, S. B., Nagarajan, H., Zengler, K., Gallo, R. L. (2013) The microbiome extends to subepidermal compartments of normal skin, Nature Communications, 4: 1431 doi: 10.1038/ncomms2441
(7) Gallo, R. L., Nakatsuji, T. (2011 October) Microbial Symbiosis with the Innate Immune Defense System of the Skin, Journal of Investigative Dermatology, 131(10): 1974-1980 doi: 10.1038/jid.2011.182
(8) Stuebe, A. (2009) The Risks of Not Breastfeeding for Mothers and Infants. Reviews in Obstetrics and Gynecology. 2009 Fall; 2(4): 222-231

(9) Roach, M. (March 213) It's a gut reaction: how other people's bacteria can cure us-extract, The guardian.
(10) O’Sullivan, A., He, X., McNiven, E. M. S., Haggarty, N. W., Lonnerdal, B., Slupsky, C. M. (2013, May. 7) Early Diet Impacts Infact Rhesus Gut Microbiome, Immunity, and Metabolism. Journal of Proteome Research. Doi: 10.1021/pr4001702

(11) Newsholme, P., Brennan, L., Bender, K. (December 2006) Amino acid metabolism, beta cell function, and diabetes. diabetes journals. Vol. 55. p. 539-547. doi:10.2337/db06-S006
(12) Eisen, Jonathan. (July 2012) Meet Your Microbes, TED.


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