Sunday, 17 August 2014

Bacteria before Birth?

The human body is not entirely human. In fact it is estimated there are around 10 bacterial cells living within the human body for every human cell present. Microbial organisms in a particular environment are termed microbiomes, and microbiomes are present in our gut, airways, mouth, and various other sites in our bodies. Thankfully these microbiomes provide many positive functions as they aid in the digestion of food, prevent the colonisation of pathogenic bacteria and can produce essential vitamins and minerals that we humans cannot produce on our own.

Perhaps the most famous of the microbiomes is the gut microbiome, as we are forever reminded to feed our “good bacteria”. Indeed each of the microbiomes found in the human body are unique. The various populations of bacteria in the gut are not identical to those found in the airways or in the vagina as both the abundance of bacteria and even the species of bacteria vary. These can also vary between individuals, it has been suggested that a gut microbiome is as unique as a fingerprint.





Intestinal cells are lined with bacterial flora (or a "microbiome") 

which is specific to each individual.

Courtesy of Pacific Northwest National Laboratory 


Where though, do all these bacteria come from? At what point in our lives are we accumulating these vast numbers of bacterial populations?

At the moment the answer is: it’s not certain. However, it’s easy to see with these vast microbiomes that perform so many functions within us how essential it is to understand how and when microbiomes are established. This importance is only amplified when we consider that microbial communities can cause oral disease and may be involved in some digestive disorders and potentially involved in obesity.

There are a few clues though that perhaps gives some insight into where and when these microbial communities are appearing. Babies possess complex microbiomes within their first of life, albeit taking several years for these to mature and settle into equilibrium. Until this time the bacterial populations can demonstrate quite dramatic fluctuations. The populations and percentages of bacteria present do display variation between babies, particularly noticeable in those who weigh less than 1200g (2lb 10 oz). This would suggest infants are being exposed to bacteria within the uterus, and babies born prematurely are failing to develop the microbiome patterns expected due to a reduced exposure time.

Previously it was believed the uterine environment was sterile but, it has been presented on several occasions that bacteria are present intrauterine and that the placenta contains bacteria, even in a healthy pregnancy. It also would appear the placenta may aid in the establishment of microbial communities. In a landmark study, published earlier this year, an American group of scientists have begun to characterise the placental microbiome and give a more detailed insight into what bacteria are present. The study published in Science Translational Medicine looks at placental tissue from 320 subjects using DNA sequencing techniques to examine the bacteria.

The exact species and percentages present varied between individuals nevertheless in the majority of cases, E. coli was found to be in highest abundance. Definitely noteworthy is the fact that the placenta possessed a low abundance of bacteria, quoted as being 0.002mg of bacteria per 1g of placenta demonstrating that although the uterus is not sterile it certainly does not contain the vast amounts of bacteria we’re used to seeing in organs. For comparison there are approximately 104 to 107 bacteria per gram of contents in the jejunum and ileum and 1011 to 1012 cells per gram in the colon.

The group then go on to compare the microbiome of the placenta to other microbiomes found within the body. Perhaps surprisingly, the microbiome did not register as similar to that found in the vagina nor in the gut with both the bactieral species and metabolic processes involved differing from both these body sites. In fact, the placental microbiome demonstrated most similarity with the oral microbiome. This garnered much interest with news outlets as a link between periodontal disease and premature birth has been suspected for many years, a quick search reveals many papers looking at both epidemiological and biological data in order to provide a link. However, the authors did not expect this finding and so the study was not designed in order to examine this similarity any further. Although there is much speculation around this fact, very little concrete evidence for the link between periodontal disease and preterm delivery can be drawn from this study.

The authors do demonstrate a variation between placental microbiomes from women who carried full term and those who did not. Both the bacterial species present in the placenta and the metabolic profile of the bacteria differed between these two cases. One must bear in mind though that the authors could not examine the placenta over the course of a pregnancy, as this would be rather invasive, so it might well be that the placental microbiome simply changes during pregnancy. Given the fact we know microbiomes of babies undergo such a radical change within the first few years of life, this does not seem such a far-fetched notion.

This study provides an overview of the microbiome in the placenta for the first time giving insight into the various bacteria and their functions. Additionally, the authors examine the influence of preterm delivery on the placental microbiome. What this study does not do is prove that bacteria are passed through the placenta from the mother to the infant, as no studies of the infant microbiome from the cases presented here were performed. The primary technique used here was DNA sequencing and statistical analysis based on the sequencing information generated and not any analysis into live bacteria and whether or not these were transferred. Nevertheless it provides further evidence the uterine environment is key in establishing the microbiomes present in the human body. 

References:
Kjersti Aagaard et al. 2014. The Placenta Harbors a Unique Microbiome

http://stm.sciencemag.org/content/6/237/237ra65
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Tuesday, 1 April 2014

Oh Immune System, You're Just Overreacting...

Your immune system is constantly working to protect you from the onslaught of bacteria, viruses and parasites that would otherwise invade your body and potentially cause disease. Ordinarily the immune system works tirelessly without us even knowing; it is only when something creeps through the defences do we actually notice our immune system. Typically only to curse it as we struggle through a work day with a full blown cold.

Not surprisingly perhaps, when our only reactions towards it are negative, the immune system can be oversensitive and respond to harmless everyday substances as if they were harmful. These substances can range from pollen to food substances to latex to penicillin, almost any substance the body encounters on a day to day basis. When the immune system next encounters the substance, it launches a full blown attack, think taking on an ant with a rocket launcher, and you won’t be far wrong.

This overkill tactic results in an allergic reaction.

It is already known the immune response initiated by an allergen differs to an ordinary immune response. When the immune barriers are breached, by a bacterium or a virus for example, cells are on hand to ingest the foreign particles and present them to the immune system. The immune system activates the correct white blood cells which start producing specific antibodies against these particles. Antibodies act as a homing system, marking the foreign particles for destruction by other immune cells. After the foreign body is dealt with the antibodies linger in the body, and are able to quickly activate the immune system if the foreign particle is encountered again.

An antibody that encounters an allergen, a substance that causes an allergy, activates a particular type of white blood cell called a mast cell. Mast cells are important in wound healing and defending against infectious agents, but are most renowned for their role in allergic reactions. Mast cells respond to allergens via a specific receptor on their cell surface, FcεRI. An antibody with an allergen binds to FcεRI and activates a downstream signalling pathway, causing the primed mast cells to release powerful signalling molecules, including histamine. These can act on the other cells within the body resulting in the characteristic symptoms of an allergic reaction.

But an allergic reaction can range from mild hayfever or a slight rash to life-threatening anaphylactic shock, so what could cause these massive discrepancies?

The response of mast cells to an allergen is now thought to be dictated by how tightly the antibody binds to the allergen, and that the strength of binding is actually detected by the FcεRI receptor. This mechanism of action has been seen in other cells; for example, yeast cells use the presence of pheromones to control their growth. The yeast cells possess receptors which recognise the pheromones and change the cell’s growth patterns depending on the levels of pheromones present in the environment. Similarly to the yeast, mast cells are thought to change their behaviour via the FcεRI receptor in response to high-affinity, tight binding of the allergen to the antibody, or low-affinity, loose binding of the allergen to the antibody, stimulation.

There are some antibodies able to bind their targets more strongly than others, generating these differences in affinity. Binding affinity influences how rapidly the antibody moves away from the FcεRI receptor, therefore antibodies with a low target affinity, dissociate away faster from the FcεRI receptor whereas antibodies with a high affinity stick around for much longer. If the antibody lingers around the FcεRI receptor it is able to keep stimulating the receptor, this translates to a greater response from the mast cell.

This was demonstrated by a team of scientists in the US by stimulating mast cells with chemicals. These chemicals bind to the same antibody but at different affinities thus changing the stimulation the FcεRI receptor receives. These chemicals actually activated different signalling pathways within the mast cell despite the stimulation initiating in the same receptor. The end response of the mast cell differed between the chemicals depending on the pathway activated. This was also evident when the team tried a similar study using mice where the mast cells again showed a differing response dependent on the affinity of the antibody to the chemical.

The change in mast cell response gives an idea into how the affinity of the antibody may change the allergic reaction experienced by an individual. However, other cells in the immune system possess receptors similar to the FcεRI receptor therefore these results may well extend beyond allergy studies. The understanding of how our immune system works is critical for us to develop new ideas and therapeutics allowing better management strategies and treatment options. 

References:

Suzuki et al. 2014. Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE https://www.sciencemag.org/content/343/6174/1021.full


Marc Daëron. 2014. Signaling Shifts in Allergy Responses

https://www.sciencemag.org/content/343/6174/982.full


Sunday, 16 March 2014

First Post - An Introduction

Hello,

Welcome to my blog and thank you for reading this post! I’m a first year PhD student in the Biology department at the University of York looking to write about all things science.

I’ll mainly be writing about molecular and cell biology as these are the topics I am most familiar with but hopefully I’ll branch out into other areas of science I find interesting! These may be articles or talks that I've attended but without the jargon we come to expect from scientists.


I hope you enjoy reading my work and stick around for further writings and musings. All comments and suggestions are gladly welcomed!