The bacteria that live in the human gut may play an important role in immune response to vaccines and infection by wild-type enteric organisms, according to two recent studies resulting from a collaborative effort between the University of Maryland School of Medicine Institute for Genome Sciences and the Center for Vaccine Development.
The first study, published online in PLOS ONE,* examines the impact of an oral typhoid vaccination on the microbiota, or populations of bacteria, in the human gut. The second study, also published online in PLOS ONE,** looks in monkeys at the impact in the gut microbiota of vaccines against Shigella, as well as exposure to wild-type Shigella, another group of bacteria that, like S. Typhi, gain access to the host via the oral route.
These studies find that higher diversity in the gut microbiota, i.e., more types of bacteria in the gut, affect the characteristics and magnitude of the immune responses to the vaccines and, in the case of exposure to wild-type Shigella, appear to be more resistant to infection. This research provides a window into how vaccines and resistance to enteric pathogens work. It also helps scientists understand more about how the "good" bacteria in the body affect human health, a growing area of research known as the human microbiome.
"Our research raises the intriguing possibility that the gut microbiota may play an important role in response to vaccines and susceptibility to enteric pathogens, or bacteria that affect the intestinal tract," says the senior author on both papers, Claire M. Fraser, Ph.D., Professor of the Departments of Medicine and Microbiology and Immunology and director of the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine.
"The results are preliminary and more research is needed. In future studies, we plan to expand the subject pool and add metagenomic analysis. Metagenomics, also known as community or environmental genomics, will allow us to look at the function of the gut microbiota and how it is changing under various vaccination schedules. This research provides a fascinating window into the human microbiome, and how the bacteria in our bodies impact our health.
Both S. Typhi and Shigella are still devastating to populations in certain parts of the world. We hope that this work might one day help to provide relief to those areas that still suffer from these diseases."
The first study analyzed the impact of an oral typhoid vaccination with an attenuated Salmonella enterica serovar Typhi (S. Typhi) on the human gut microbiota. While typhoid is not considered endemic in Western countries today, it is estimated that there are over 20 million illnesses associated with typhoid worldwide, particularly in south-central and south-east Asia.
Scientists at the Center for Vaccine Development and other institutions have long been working to develop an improved oral vaccine to prevent the disease. Differences in the effectiveness of experimental vaccines have been attributed to heterogeneous immunogenicity among subjects, host genetics, nutrition, socioeconomic status and other factors.
Researching the impact of the composition of intestinal microbiota is a new approach made possible by state-of-the-art advances in high-throughput sequencing technologies. The cutting edge facilities at the University of Maryland Institute for Genome Sciences generate huge quantities of data far more quickly than older technology. Similarly, advanced instrumentation and immunological techniques at the Center for Vaccine Development have, and continue to provide significant insights into the immune responses that are likely to correlate with protection.