Sunday, April 19, 2015

Defining Microbiome Engineering and Our Realistic Expectations

Microbes, including bacteria, viruses, and fungi, are all around
us. <Source>
Most of us are aware of the impacts the human-associated microbial communities (the human microbiome) have on our health. These communities consist of the bacteria, fungi, viruses, and other microbes that live on and in our bodies. As I have mentioned in previous posts, the field of human microbial ecology has really taken off in the past decade, primarily as a result of next generation sequencing that has powered our scientific abilities to discover a more robust human microbiome than previously appreciated.

With this new understanding of human microbes, there has also been a greater interest in targeting that community with therapeutic interventions. To date, we have seen this result in a renewed scientific interest in probiotics, prebiotics, and even fecal microbiome transplant therapies. Overall these therapies are focused on altering the human microbiome to promote health, which is ultimately getting at the idea of microbiome engineering. The term microbiome engineering is being used more and more, and the field shows great promise, but what do we actually mean by "microbiome engineering"? Where is the field at now, and what are the prospects of the field moving forward? These are the questions we will address in this post.

Defining Microbiome Engineering

Before we get into the potential benefits of microbiome engineering, I want to actually define the term. I think the term microbiome engineering is a little confusing because there seems to be a lack of consensus as to what it actually is.

To start, we can remind ourselves that engineering is defined as "the application of science and mathematics by which the properties of matter and the sources of energy in nature are made useful to people". I would even summarize this further as engineering being the application of scientific understanding to solving real world problems. We see this is mechanical engineering, chemical engineering, and software engineering, to name a few. But what about microbiome engineering? As another form of engineering, I would say that microbiome engineering is simply applying our scientific understanding of the human microbiome to solving real medical problems.

Now we defined the term "microbiome engineering", but we landed on a very broad definition. This is still very important because, as we discuss this topic here and with others, it will be important to remember that this is inherently a broad term. I often see people using the term to define a very specific type of microbiome manipulation (such as introducing engineered bacteria into the human microbiome), and I think this is contributing to the confusion around the term. If we want to successfully communicate our specific applications of microbiome knowledge, we need to be more specific than simply referring to it as microbiome engineering.

What Can We Expect From Microbiome Engineering?

So now we have a specific definition for "microbiome engineering". What we really want to know is where the field is at right now, and more importantly, how will it affect our lives in the years to come. Without adding more hype to the field (and there is plenty of hype around the promise of microbiome research), I think we can reasonably expect to see some real microbiome engineering advances in the next few years. Here I will briefly outline what I think we can realistically expect to see in the not-so distant future.

Phage therapy involves phages (pictured) attaching to,
infecting, and killing their bacterial host. <Source>

1. A renewed interest in microbiome engineering through bacteriophage therapy

The first, and honestly one of the most exciting advances for microbiome engineering is going to be bacteriophage therapy. I have talked about this before, but as a reminder, bacteriophage therapy is the use of bacterial viruses (bacteriophages, or just called phages) to target and kill specific bacteria in an infection. This therapy was largely abandoned upon the discovery of antibiotics, but has gained renewed interest over the past few years. Phage therapy is a welcome alternative to antibiotic usage because it is targeted to specific bacteria and will not affect most healthy bacteria, it can kill antibiotic resistant bacteria, and it can reach bacteria that antibiotics cannot, such as those in biofilms. Additionally, this is a promising microbiome engineering tool because it can specifically modulate the composition of our bacterial communities.

There have already been some early stage clinical trials that have shown safety and even efficacy in treating bacterial infections, some of which were antibiotic resistant, with bacteriophage therapeutics. It is therefore reasonable for us to expect a renewed interest in this medical technology in the coming years. Furthermore, I would say it is reasonable to expect to see phage therapies used in medicine in the near future, in light of the Intralytix approved phage use on food, the European clinical trials, and the awesome Gates Foundation grant initiative for microbiome engineering using phages.

2. More robust research into probiotic and prebiotic therapies

Like phage therapy, probiotic and prebiotic supplements and therapies are nothing new. These have been around for ages, but have recently gained a lot of attention as we understand their effects in the context of the human microbiome. In fact, Fecal Microbiome Transplant (FMT) therapies, which I would say are a type of probiotic therapy, are promising in current clinical studies. There is also an increasing research interest in pill-based therapies, which to date have shown conflicting efficacy in clinical studies. We can realistically expect to see an increased push for probiotic and prebiotic research in the coming years. As far as the specific miracle probiotic and prebiotic pills, see point four below.

3. Bacterial vector therapies

C. difficile (pictured) is a current microbiome
engineering target through fecal microbiome
transplant therapies. <Source>
In addition to engineering the microbiome with phages, natural bacteria, and nutrients, we are also seeing cool research into the use of bacteria as vehicles for genetic processes that will promote health. As an example, these bacteria are being modified to secrete drugs when they sense a certain disease state, such as secreting anti-inflammatory drugs when they sense inflammation (see reference below). They are also being developed to secrete molecules that "inactivate" Cholera causing bacteria, so that they can be delivered to the stomach to treat Cholera. Honestly, I think that these are promising therapies, but still relatively early in development. These are complex systems and will take many years to get to the point of wide clinical usage. Therefore, while I think we might see this in our local hospital in the future, it is still going to likely be more than a decade before we see this widely available.

4. What not to expect from microbiome engineering

My last point is what not to expect from microbiome engineering. It is exciting to speculate on what awesome microbiome technologies will be available in the future, but it is unreasonable to expect them in the near future. Especially something like a simple probiotic pill that will cure obesity, which would be amazing, but is still quite far off. The microbiome engineering field remains in its infancy, which means these medical advances will take time to mature into widespread and helpful resources. While I think it is possible, I think it is important to be realistic in that these advances are still a relatively long ways off, and we have a lot more to learn about the human microbiome and how it interacts with the human body.


To wrap this post up, we discussed what microbiome engineering actually is, and what we should be thinking about when we use that term. We also went through some realistic expectations we can have from the microbiome engineering field, including phage therapies, probiotics, and prebiotics. It is also important to remember that many of the more advanced technologies that are being developed are still a long ways off from being commercially available, and we still have a lot to learn about the human microbiome as a whole.

Works Cited

Sonnenburg, J. (2015). Microbiome Engineering Nature, 518 (7540) DOI: 10.1038/518S10a


  1. Yeah there is a lot of hype around the field, much like the hype around the human genome a few years ago. There are certainly amazing and promising technologies coming form the field, we just need to remember that drug development takes time.