A Library of Human Gut Bacterial Isolates Paired with Longitudinal Multiomics Data Enables Mechanistic Microbiome Research

By Dr. Katie E. Golden, MD

One of the biggest challenges in understanding the relationship between a human host and their gut flora is the lack of robust, longitudinal data sets to study changes in the microbiome over time. This would allow us to study the factors that affect both stability and fluctuations in the microbiome, how this affects development and progression of human disease, and also supply a library of isolates to test future scientific hypotheses regarding the role or utility of specific bacterial strains. Recognizing the need for such a resource, the Broad Institute and OpenBiome Microbiome Library (BIO-ML) now supplies a comprehensive collection of nearly 8,000 intestinal bacterial isolates, paired with nearly 4,000 genome sequences, to serve as an open access investigational resource. In a recent publication1, researchers use the databank to make important observations regarding bacterial population trends over time, showing the utility of such a valuable data library and laying groundwork for future research to come.

Researchers are currently working hard to learn how we can engineer the microbiome to treat a variety of human diseases, thus broadening the spectrum and improving the efficacy of treatments like Fecal Microbiota Transplant (FMT). The OpenBiome is a stool bank that has already provided material for nearly 50,000 fecal transplants for patients suffering from recurrent Clostridium difficile infections, and we are just beginning to uncover the broader use of this therapy in new disease areas (Inflammatory Bowel Disease, liver disease, neurodegenerative disorders such as Parkinson’s disease, malnutrition and infection). A databank like the OpenBiome is a resource that can be harnessed for cultivation of isolated strains and longitudinal sampling, which is invaluable in understanding bacterial-host dynamics and designing future clinical trials.

In this paper, investigators made a number of important observations that introduce us to the potential of this developed library. First, they investigated whether the cultured isolates from BIO-ML mimics the diversity seen in culture-independent (in vivo) methods, and found that bacterial genus-level diversity was well preserved in the stool bank. They were also able to culture 159 of the ‘most wanted isolates’ (n=485) that lacked cultured representatives, which are significantly associated with human disease. In conjunction with their high-quality genome assemblies, the generated longitudinal collection provided the necessary material to analyze microbiome changes (down to the level of single nucleotide polymorphism) across populations as well as over an individual’s lifespan. They ultimately found that microbial species exhibit stable population abundances both within and across individuals over time. The observed variation of bacterial metabolites within an individual, presumably from factors such as diet or inflammation, was seen in amino acid levels rather than bacterial taxa. Inter-individual variation variation, by contrast, was seen in bile acids.

This paper highlights just the beginning of the potential uses for the BIO-ML. In utilizing isolates and culture-based work, we will be able to advance microbiome research to understand how gut bacteria responds to changes in nutrition, pharmaceutical interventions, and immune responses. With accompanying genomic data, this could lend important insight into strain dynamics within an individual that has the power to inform future microbiome engineering and therapies for advanced, personalized treatment of disease.

Poyet M. et al., Nat. Med. 2019. DOI: 10.1038/s41591-019-0559-3