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The New Frontier: Unlocking the Opportunities of the Microbiome

Updated: Jul 19

The New Frontier: Unlocking the Opportunities of the Microbiome

July 22, 2021

By: 20/15 Visioneers, Leaders in Science and Technology A Comprehensive Microbiome Industry Perspective

Published on 22nd July 2021 “The microbiome in its extreme complexity has surrounded us all these millennia yet only recently, through our evolving understanding of biology and utilization of advanced technologies, are we beginning to unravel its applicability enabling major discoveries” - John F. Conway

Contents

Executive Summary

1. What is the Microbiome?

2. History: Microbiome Technologies

3. Microbiome in Industry

3.1 Microbiome in Therapeutics

3.2 Opportunities for Microbiome Research in Biopharma/Drug Metabolism

3.3 Engineering Microbiome Therapeutics

3.4 Microbiome in Food, Nutrition and Wellness

3.5 Microbiome in Dermatology, Cosmetics and Personal Care

3.6 Microbiomes in Agriculture and Soil Management

3.7 Microbiomes in Aquaculture and Animal Health & Nutrition

4. Observed Challenges With Microbiome & Multi-Omics Data Management & Analysis

5. A New Generation of Scientific Data Management & Analysis Platforms for Microbiome Data & Processes are Needed

5.1 Eagle Genomics & e[datascientist]

6. Other Vendors

6.1 DNANexus

6.2 Illumina (BlueBee)

6.3 BigOmics

6.4 Metabolon

7. Conclusion

8. References **Acknowledgement to all the contributors to this document from both Eagle Genomics and 20/15 Visioneers. It was a highly collaborative and team effort! Executive Summary

Microbiomes are fundamental to, and interact with, every aspect of life on our planet. Despite this fact, the scientific community has, until only recently, underestimated the complexity and systems-like involvement of these highly complex microbial entities. Having now recognized their vital importance, focus has now turned towards the need to catalogue, understand, and proactively manage the microbiome. Given the multi-dimensional and complex nature of microbiome data, it is understood that this task could be a significant challenge for decades to come. Overcoming this challenge, however, will provide innumerable rewards with significant positive impact on the world and society overall, including: Accelerating the development of innovative medicines, improving food production and producing industry-leading, sustainable consumer goods, in addition to potential positive effects on already-threatened environments and ecosystems.

Common key themes and requirements have emerged repeatedly across a number of microbiome studies, including:

The magnitude and complexity of microbiome data and data types

Interactions between microorganisms, humans and animals

The potential to use the microbiome to protect and improve human and animal health while reducing the impact of human related activity on the biosphere

This paper summarizes the history of microbiome exploration, understanding, and discovery to-date, and describes multiple product and market opportunities that responsible, well-informed exploitation of microbiome science could unlock. The microbiome is a perfect example of a large and complex domain that will ultimately unlock secrets in biology and hopefully improve quality of life for all beings. At the core of many large science and technology initiatives currently focused on promoting access to, handling and analysis of microbiome data, is the need for more effective data and process management. Unfortunately, today’s research and development environments have become increasingly complex, requiring forethought and planning to successfully integrate the most advanced scientific informatics, technology, and processes into established corporate cultures. Many R&D environments are riddled with inefficiencies, due to historically poor data curation and management processes that don’t comply with current FAIR data practices, relying instead on outmoded technology stacks that suffer from excessively deferred change management. This has led to a marked decrease in the rate of innovation at many organizations, as well as wasted time and effort devoted to incessant data wrangling, inconsistent reproducibility and replication of experiments, and processes that do not readily transfer and/or scale-up to further stages of development.

Top technological platform players have been addressing current challenges related to microbiome data analysis with tool stacks that can help perform contextualized data capture, curation, and reporting on microbiome experiments and data. Organizations contemplating a deeper push into advanced microbiome/multi-omics science are recommended to carefully consider and evaluate multiple partner-vendor offerings before committing resources to building a bespoke microbiome data and process environment. This paper highlights leading platforms and technologies offering the most up-to-date informatics and analytics infrastructures that have been designed to dramatically increase knowledge, understanding and discovery. A handful of microbiome software companies have developed numerous case studies that illustrate both the challenge, the approach, and the outcomes of omics-based microbiome studies. These case studies run the gamut from identifying sustainable compounds for use in consumer “everyday” products to identifying biomarker signatures for disease conditions, including the generation of prioritized and curated datasets to uncover all kinds of associations with health and disease prognosis. 1. What is the Microbiome?


The microbiome can be defined as a characteristic microbial community occupying a reasonably well-defined habitat with distinct physio-chemical properties. Therefore, the term “microbiome” refers to the microorganisms involved as well as their entire “theatre of activity,” both of which contribute to the formation of specific ecological niches. The microbiome, which forms a dynamic and interactive micro-ecosystem prone to change in time and scale, is integrated in macro-ecosystems including eukaryotic hosts, and is crucial for their functioning and health (Berg et al., 2020).

Modern medicine and consumer culture have been long on a crusade to eliminate health-threatening bacteria by using antiseptic products and antibiotics. Although this approach has delivered significant improvements in treating and controlling infectious diseases, it is becoming clear that declaring a war on Nature has come at a price. This price has rested mostly on the lack of understanding of the microbiome as well as its complex relationships with human health and wellbeing (depicted in Figure 1).

Figure 1 - The extensive impact microbiomes have on life and the planet (from Finbow, 2019) Just as modern agricultural practice now incorporates the idea that many insects together can be beneficial, rather than being considered to be harmful and unwanted pests, we are learning – or perhaps, remembering – that not all microbes are bad. It’s much more difficult to understand and manage the significant positive contributions a complex microbiome can make to the health of humans and livestock, as well as to agriculture and aquaculture, than to identify specific pathogens that unambiguously manifest in disease. The scientific community is getting more sophisticated in its understanding of the complexity of the host/microbiome relationship in the context of a symbiosis that has emerged over millions of years. This inseparable relationship continues to evolve as globalization and modern life impact the biosphere, whether in our outer environment or within our own bodies. Some have also argued that over the last seventy years or more, that this relationship has been breaking down. As a result, the microbiome has become more vulnerable to environmental changes, and hosts have also become less responsive to any microbial-related benefits.

The good news is that tools are becoming available to scientifically track, study, measure, and disentangle complex chains of causality that would otherwise be out of reach to individual researchers and/or research organizations. It seems necessary to create scientific networks and platforms whose components will benefit from shared data in a synergistic cooperation. This will allow for increasingly informed interventions, the consequence of which is that health and wellness management stands poised to reclaim its place alongside disease eradication as a critical step in the progress and evolution of living beings. 2. History: Microbiome Technologies

Ancient practice recognized the importance of the microbiome long before modern scientists defined it. The first reported use of feces with therapeutic purposes dates from the Eastern Jin Dynasty (3rd-4th century AD) where patients suffering from severe diarrhea were successfully treated with a human fecal suspension known as “the yellow soup.” Though the first formally approved microbiome therapy would not arrive for another 1500 years, technological advances have increasingly allowed us to understand and nourish beneficial microbial communities, while identifying and treating the bad. Today, novel tools are enabling us to harness the power of microbes across industries, applying and ultimately designing microbes to usher in a biological revolution.

The first Western descriptions of human-associated microbiota date back to the 1670s–1680s, when Antonie van Leeuwenhoek started using his own newly developed, handcrafted microscopes. In a letter written to the Royal Society of London in 1683, Antonie described and illustrated five different kinds of bacteria (he called them animalcules at the time) present in his own mou