Microbiome Engineering: A New Generation of Ideas (2020)

John C. March Matthew Wook Chang There has been considerable hype surrounding synthetic biology since its inception. Researchers laid claim to the potential of finally realizing our biological future through genetic manipulation. Unfortunately, early work indicated just how challenging harnessing biology to work for us in the way that electricity and chemistry already had. However, over the past 15 to 20 years the field has learned a great deal about the possibilities and pitfalls of forging microbes for specific applications. This issue presents some of the successes that have finally begun to pay off for this still-nascent field. We have gathered six articles from some of the most promising young minds in the field of synthetic biology: looking for their take on where the field is going and to share with the community their latest developments. You will find herein a meticulous review by Rottinghaus, Amrofell, and Moon, describing the very latest in microbial engineering for medical applications (https://doi.org/10.1002/biot.201900319). It is in this area that the field has made the perhaps most progress and this review captures some of the most promising efforts in diagnosing, treating, and preventing disease. The authors also discuss one of the biggest bottlenecks in the development of new strains to treat novel diseases: that of an experimental system akin to the high throughput systems that are frequently used to build strains. The limits of the animal model system are also discussed with ideas about how to replace it. An article by Tham and co-workers digs deeper into one specific medical presentation, that of atopic dermatitis (https://doi.org/10.1002/biot.201900322). Here, the concept of the biome is stretched to include skin microbes. Such an approach holds promise for many epidermal maladies. The authors discuss the ramifications of altering the skin microbiome to have less of Staphylococcus aureus and more “beneficial” microbial communities. Such tinkering can lead to unintended dysbiosis and the authors discuss how this can be managed. One of the ways that microbial pathogens evade detection and removal from the body is to gather in biofilms. The paper by Liu and co-workers from Chun Loong Ho's lab examines the role of the biofilm in protecting harmful bacteria and the biochemical processes that maintain it (https://doi.org/10.1002/biot.201900320). There are three classes of attack used against biofilms: physical, chemical, and biological. This review presents these with a perspective on what works and what is unlikely to do so. Over the last ten years, the relationship between gut microbiomes and obesity has been increasingly elucidated. Lim, Lee, and Ooi have provided some clues as to what causative mechanisms in that relationship are (https://doi.org/10.1002/biot.202000013). The explosion of obesity as a global pandemic has been widely reported. What is less well-known is how obesity and factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits, and use of antibiotics can all play deciding roles in gut microbial health as well as in obesity. Connecting the temporal events is challenging and this review gives the reader a great place to start putting together the pieces of this complex relationship. It has been known for some time that the biochemical landscape of the human intestine changes constantly with changes in our health and diet. What has been much less known is how this plays out in controlling metabolism. The interaction between microbial populations in the gut and their host is mediated through numerous chemical transformations and exchanges. One such exchange has been linked to several metabolic disorders, including diabetes. Sasaki, Sasaki, and Kondo present their original research on how molecular structure plays a role in the balance of organic acids in the large bowel (https://doi.org/10.1002/biot.201900523). The same acids that facilitate interspecies communication in the gut play a role in directing the body's response to nutrients. Changes in how gut bacteria parse propionate, acetate, and butyrate can have profound impacts on how we metabolize and respond to nutrients. This fascinating paper dives into the conversion chemistry of different metabolites that keep metabolism tightly regulated. Finally, the last article from Lei Dai's group revisits the concept of “live biotherapeutics” and how they can be improved upon to be more effective with fewer side-effects (https://doi.org/10.1002/biot.202000155). This article deftly moves between many of the success stories now happening in synthetic biology. From phage therapy for controlling microbial population densities in a consortium to deploying engineered bacteria that can recognize a tumor, swim to it, and dispatch it from the intestine, the authors do a great job of presenting material that demonstrates that success has started to infiltrate the synthetic biological ranks. These are just a handful of bright young investigators, building more sustainable and compatible technologies for healing. It is expected that a future issue of this magazine might include work on sustainable technologies, such as in chemical production or waste conversion to value-added products or electricity from batteries comprised of electrochemical microbes. We are proud to present these innovators of the biological realm and hope you will check back regularly to see what they and yet to be named others are working on next. Thank you and enjoy!