‘With reference to the Human Microbiome Project (HMP), discuss how the application of
metagenomics is enhancing our understanding of how microbial communities influence
human health and disease’
Introduction:
Humans, over the course of their life time are colonised by a huge amount of commensal bacteria.
These bacteria make up the human microbiome, and it is through the HMP that we have begun to
consider ourselves as a supraorganism made up of both human and microbial components (8). The
metagenome, defined as the collective genetic potential of the human microbiome (3), is thought to
affect health and disease in humans in many different ways. The HMP followed on from the Human
Genome Project and has been used to sequence the metagenome of 250 ‘normal’ volunteers. It had
three main aims, the second of which being ‘to determine whether there are associations between
changes in microbiome and health/disease by studying several different medical conditions’ (1).This
aim is of particular interest as it explores how the body and microbiome work together to maintain
healthy homeostasis and how changes in microbiome may cause disease.
Discussion:
Metagenomics is a term that umbrellas many research techniques to study the human microbiome
as a whole. By using several different techniques together, metagenomics maximises the
understanding of the interactions between individual organisms in our microbiome and how our
body interacts with these organisms. One of the main techniques encompassed by metagenomics is
16S rRNA sample sequencing; this technique looks at highly conserved genes to get compositional
data for a microbial community. Whole genome shotgun sequencing is another technique which
studies the whole genome by looking at smaller chunks of DNA, it then puts the data back together.
Shotgun sequencing can also be used to look at the compositional data of a microbial community
but unlike 16S rRNA sequencing it can also be used to create functional and genetic profiles for the
communities (2). Metagenomics, due to its use of several methods, avoids the problems that many
past techniques have encountered such as the unculturability of some bacteria (13), by avoiding
these problems we get a more accurate representation of a ‘normal’ human microbiome.
Until birth humans contain only our own cells, but from birth we are colonized with an enormous
amount of microbial life (3), these microbes are essential in many aspects of human life from
development to digestion. The four main sites for microbial colonisation were studied during the
HMP, the mouth, gut, skin and vagina (1). The human body contains at least 10 times more bacteria
cells than human cells (15) so there are substantial differences in the types of bacteria present
between individuals, it only through using metagenomics that we can see what makes up a healthy
microbiome. The gut contained the most diverse set of bacteria both between individuals and in the
amount of different types of bacteria present (3). The gut microbes help us harvest energy from food
we digest, changes in gut microbes are thought to contribute to IBS, diabetes and obesity (12).
One study by (7) looked at the differences in adult gut microbiomes and their relation to obesity. It
found that whilst the primary cause of obesity is the intake of too many calories that in adults with
obesity there was a trend of reduced biodiversity, and changes in the expression of bacterial genes
and metabolic pathways. The next step for this study is to determine, with the aid of metagenomics,
whether changes in the gut microbiome is a cause or effect of obesity. It has begun to be accepted
that through the westernised culture of eating generic, uncontaminated foods and washing often,
there has been a significant decrease in microbial diversity (4), possibly leading to an increase in
disease.
Vaginas were found to have the lowest microbial diversity of the sites studied by the HMP and,
unlike in the gut, higher diversity caused problems both during and when not pregnant (11). A study
by (14) showed that women who don’t suffer from bacterial vaginosis had between 1-6 different
species in their vaginal fluid whilst women suffering from bacterial vaginosis had between 9-17 types,
whilst this information was previously known it is through understanding the metagenomics of these
communities that we can start to develop new, more accurate treatments for this condition, and
others like it. This year a study that lead on from the HMP by (2) was outlined, it aims to look at
three human microbiome associated human conditions, how the vaginal microbial diversity affects
preterm birth was one of these. (2) describes that whilst the survival rate of neonates has increased
in the last 25 years, the incidence of severely premature birth has not decreased. They hypothesise
that as premature birth is often caused by an infection that by studying and understanding the
metagenomics of the maternal microbiome that we will be able to grasp the differences from the
norm that contribute towards a preterm birth. The use of metagenomics in this context, to look
further at known but not well understood health problems, will undoubtedly enhance our
knowledge of health and disease. Eventually the data from such studies will hopefully be translated
into treatment plans to help prevent or revert changes from a normal microbiome.
Conclusion:
Our knowledge of the human microbiome is ever expanding due to metagenomics, I believe that we
are only just beginning to touch on the ways in which metagenomics could potentially expand our
understanding of health and disease. By combining several different sequencing techniques and thus
avoiding problems faced by previous studies of the human microbiome, through the HMP we were
able to realise just how vast and diverse the communities within our body are. The HMP looked
largely at what makes up a healthy microbiome, and it is studies which are starting now, following
hypotheses created from the results of the HMP, to look at what happens when the human
microbiome deviates from the norm which will be of really impact on our understanding of disease.
Expanding on this will enable us to diagnose and treat diseases more effectively; more specifically if
we are able to define what is missing or abnormally present in an individual’s microbiome, we may
in the future be able to be cater treatment plans to the needs of the individual’s microbiome.