June 15, 2016
Microbes like bacteria and viruses are closely tied to many aspects of human health. They help us digest the food we eat. Microbes are indicators for the quality of the water we drink. And can spread disease in the air we breathe. Using Illumina’s genomic technology, researchers are unraveling the secrets of organisms that were previously impossible to study with high resolution, providing insights into clinical microbiology, industrial microbiology, and human and animal health and disease.
Like so many applications of Illumina next-generation sequencing (NGS) technology, understanding the genetics of bacteria, viruses, and other microbial organisms begins with basic research. The genomic technology and applications described in this video empower researchers to develop reference genomes, allowing easier characterization and comparison of organisms. The technology also allows researchers to identify and study the diversity of microbial communities. Before the development of next-generation genomic techniques, many basic questions involving functional characteristics, evolution, and the interactions within microbial communities could not have been addressed.
Sequencing-based metagenomics approaches can be used to study all the organisms and their abundance present in a given environment or sample.
A very active area of this type of research is examining the interactions between the gut microbiome and human health. Armed with a better understanding of what bacteria characterize a healthy gut or a dysfunctional gut (and how a person might move from one category to another), it is hoped that new discoveries will aid in understanding the relationships between lifestyle, diet, and disease. The American Gut Project is one ongoing example of citizen science and self-sampling that will further this understanding. Another research effort, looking at the microbiome of hunter-gatherer populations in different parts of the world, found unexpected similarities in the gut microbiomes of populations despite geographical separation.
The results of these and other metagenomics studies may have great impact on the ways humans trade bacterial and viral infections. For example, Michael Sadowsky, PhD, used NGS to monitor the replacement of gut bacteria following Clostridium difficile infection. His research demonstrated how fecal transplant procedures could help restore the balance of healthy gut bacteria.
But there are also efforts underway to understand environmental genetic diversity and the role that naturally occurring bacteria play in different ecosystems. Examples include profiling the microbial community living along the Mississippi River or studying bacteria present at a Superfund site and discovering that they are breaking down the pollutants humans have added to the environment. For the rapidly expanding field of environmental microbiology, NGS is becoming a powerful tool to help researchers determine if remediation efforts are needed, or to measure their relative success in environmental restoration.
Public health scientists and epidemiologists are always looking for new clues about how diseases are spread and how we can prevent and better control outbreaks. For generations, epidemiology has taken a field-based approach with researchers asking the people who got sick questions about who was where and when. This approach can sometimes identify the source of a problem, such as in a situation where everyone who got sick ate at a particular restaurant, or worked in the same office building, but field epidemiology is limited in the information it can provide, and the accuracy of that information.
In contrast, NGS enables molecular epidemiology. Instead of asking the people who got sick questions, genomics is used to examine genetic relationships of microbes derived from person to person, animal to animal, or place to place. To respond to outbreaks, public health officials need to know where transmission might have occurred, but also what genomic changes in a given pathogen were transmitted – information that is only possible when a researcher can compare the genome sequences from individual samples. An example can be found in this case study of how Ebola moved into humans.
While stopping the spread of Ebola is requiring a multidisciplinary approach, genomic molecular epidemiology is useful in ongoing monitoring efforts and in pinpointing methods of transmission, as in this case reported in the New England Journal of Medicine where a woman died of Ebola transmitted 155 days after her sexual partner’s blood had tested free of the disease.
In addition to helping epidemiologists track and respond to pandemics, NGS can also assist clinical microbiology laboratories with key information on whether organisms are bacterial, viral, fungal, or parasitic, and what contributes to pathogenicity, such as drug resistance or immune evasion. Clinicians recognize that diagnostic guessing-games jeopardize patient care because delays in the identification of microbial pathogens increase the risk of ineffective treatment and spread of infection. As this case study describes, NGS can offer a path forward for the many infections that cannot be characterized today. While researchers can successfully use NGS to identify microbial pathogens, there are operational, regulatory, and strategic questions that require answers to enable the widespread standardized adoption of NGS in clinical settings.
Agriculture and Food Security
Beyond basic research, metagenomics, outbreak monitoring, and clinical microbiology and virology applications, there are a myriad of other ways microbial genomics can be used to improve human health and safety.
There are applications to food science and safety. Microbes influence the flavor of many foods we eat, such as wine and cheese. NGS tools are enabling food science labs to identify the microbial strains associated with better tasting foods. Other pathogens that contaminate food like Salmonella, Listeria, and E. coli, cause millions of cases of foodborne illness. Likewise, NGS can be used in food quality control operations, either by food producers, government regulators, or food companies downstream, to prevent the spread of foodborne illnesses by identifying dangerous microbes before food ends up on consumers’ plates.
Another surprising application of NGS can be found in agricultural microbiology. Microorganisms in soil, including bacteria, fungi, and other organisms, play an important role in the breakdown of organic matter and in the transfer of soil nutrients to plants. In doing so, they can be critically important to food production and other agricultural applications. In addition, the technology can be used to identify and map pathogens infecting food crops (case studies for sweet potato and cassava).
NGS technology is also an important tool for monitoring the health of agriculturally important food sources and for protecting other animals including pets, service animals, animals living in zoos, and wild animal populations. NGS technology can be used to sequence, study, and ultimately help stop animal epidemics, such as fatal viruses in pigs. And similar to human disease monitoring, genomic approaches can also be used in characterizing and tracking disease in individuals and animal populations.