Life in the superorganism known as ... you

Ryan Baker-Branstetter

They say that there are certain things that you can't unlearn.  When I tell you just how many bacteria inhabit the human body, you may find out what I'm talking about.  But not to fear.  Many of these commensal bacteria have benefits to both us and the bacteria.  Most people have heard about the wide variety of microscopic organisms that have creative and awful ways to kill us, but usually the beneficial microbes are swept under the proverbial rug and not given their turn in the microscope spotlight.  While Matteo Vaiente’s delightful blog focused on the role of commensal bacteria and their role in digestion, we’re going to focus on some of the other influences, specifically on how they help the human body defend against pathogens.

First off, let's talk about these "commensal" bacteria, as they are commonly referred to.  Commensalism is a term used to describe a relationship between two species in which one organism benefits without affecting the other.  In terms of this relationship, a much more appropriate term would be mutualism, in which both organisms benefit.  However, the industry standard is “commensal bacteria” and much of the functions of these bacteria are unknown, so we’ll use this as a blanket term for the bacteria that we peacefully coexist with. 

It’s a fair question to ask just how “us” we actually are, considering that commensal bacteria outnumber our own cells by about 10 times.  The greatest numbers of these bacteria are found in the digestive tract, but they are also found in the mouth, respiratory tract, skin, and reproductive organs.  They have been shown to interact with host metabolism, produce nutrients usable by human cells, and facilitate immune system development. 

Protection against pathogenic bacteria is an important role of the commensals living inside us.  Physically preventing adhesion and nutrient acquisition at the mucus layer is one of the first lines of defense that commensals provide.  Another defense mechanism is to produce bacteriocidal compounds such as short-chain fatty acids, including those produced by Lactobacilllus species commonly found in yogurt.  They also serve an important role is development of certain immune cells.  Studies have been performed using mice that lack commensal bacteria, and they have shown increased susceptibility to bacterial, viral, and parasitic infections.

 Yogurt as most people know it...

 And a bit closer look (400X).

Given the important role of pathogen defense, there has been a focus recently to manipulate intestinal flora to more efficiently protect against invaders.  One of the most interesting studies utilized the quorum sensing system found in Vibrio cholerae, the causative agent of Cholera.  Quorum sensing is a mechanism for bacteria to communicate with each other using small molecules called autoinducers, which are explored in more detailed in Michael Wade’s fascinating blog.  When V. cholera concentration increases, certain autoinducers reach a level that decreases the expression of factors that facilitate greater pathogenesis.  Mice treated with E. coli engineered to produce this molecule showed significantly resistance to colonization by V. cholerae, Utilization of the quorum sensing response was also used to combat Pseudomonas aeruginosa infection. E. coli that sensed P. aeruginosa using a quorum-sensing system subsequently released chemicals that inhibited growth and biofilm formation.

P. aeruginosa growth and biofilm formation with (Left) and without (Right) engineered E. coli.

Commensal bacteria engineering is definitely a promising approach to enhance human health in the future, but certain complications need to be addressed while developing this technology.  First, an effective system of delivery needs to be developed that will allow colonization in the correct location with damaging the bacteria or the host.  Another issue is control over colonization, maintaining a concentration high enough to be effective, while preventing overcolonization.  From a more long-term perspective, effect on pathogenic genomes from these preventative measures would have to be assessed, including development of resistance.

Commensal bacteria play an amazing role in our lives.  They have long been in the shadows while outnumbering our own cells and playing critical roles in immune system development and nutrition.  Over 70% of the bacteria that reside in our guts have never even been cultured outside the human body.  There is much more to be discovered about the superorganism that we consider to be “us”.


References:

1. Goh, Y.L., He H.F., and J.C. March. 2012.  Engineering commensal bacteria for prophylaxis against infection.  Current Opinion in Biotechnology 23:924-930.

2. Tlaskalova-Hogenova, H., Stepankova, R., Kozakova, H., Hudcovic, T., Vannucci, L., Tuckova, L., Rossmann, P., Hrncir, T., Kverka, M., Zakostelska, Z., Klimesova, K., Pribylova, J., Bartova, J., Sanchez, D., Fundova, P., Borovska, D., Srutkova, D., Zidek, Z., Schwarzer, M., Drastich, P., and D.P. Funda. 2011. The role of gut microbiota (commensal bacteria) and the musocal barrier in the pathogenesis of inflammatory and autoimmune disease and caner: contribution of germ-free and gnotobiotic animal models of human diseases. Cellular & Moleuclar Immunology 8:110-120.

3. Wardwell, L.H., Huttenhower, C., and W.S. Garrett. 2011. Current Concepts of the Intestinal Microbiota and the Pathogenesis of Infection. Current Infectious Disease Reports 13:28-34.

Image References:

1. J.R. Leverentz. How to prepare yogurt with pro-biotic acidophilus starter. Retrieved from  http://www.leeners.com/yogurt/how-to/yogurt.shtml

2.  Shanghai American School Student Blogs. Bacteria in yogurt lab. Retrieved from
http://blogs.saschina.org/katherine01pd2016/2011/04/12/bacteria-in-yogurt-lab/

3. Scientific American. Scientific American June 2012. Retrieved from http://www.scientificamerican.com/sciammag/?contents=2012-06