Microbes are present in plants (roots, stems, and leaves), soils, and humans (lungs, skin, and gut). They confer immunity and support life. Microbiome science has evolved rapidly. Over the years, a quick integration in biology, public health, and clinical translation has taken place while studying varied aspects of the microbiome, particularly the human microbiome. Currently, clinicians, policymakers, and public health researchers have focused on microbiome-based opportunities. As a result, this field of science is growing at a rapid pace.
Evolution of Microbiome Science
Microbiome science research deploys omics and synthetic biology to understand better and modify the pattern of microbial communities of fungi, bacteria, and archaea. Even though microbiome science has gained momentum, very little is known about its contribution to shaping the Earth and promoting human health.
Compared to plant or soil microbiomes, human microbiome science has progressed at a greater speed in the past decade. The development of the Human Microbiome Project is a great step that can be widely used in public health practice upon completion. Recently, many schools of public health, governmental agencies, the general public, and healthcare practitioners have incorporated microbiome science in their institutional infrastructure or daily activities.
Over the years, microbiome science has evolved rapidly in different areas. Besides exploring the different types of microbes from various sources, there has been progress in methodology, databases, and application of these microbes to improve human health and the environment. Some of the key areas where microbiome science has evolved are discussed below:
Biological Discovery and Epidemiology
Human microbiome science has discovered novel biomarkers, molecular mechanisms, and therapies with immense public health potential. Several studies have also indicated that environmental microbial communities interact closely and impact human health. This can be explained using the example of how the agriculture/livestock microbiome improves the quality and quantity of food that affects human well-being.
Microbiome epidemiology is associated with molecular epidemiology, which concerns the genetic association or discovery of gene-expressed biomarkers. The microbiome can be used as a potential biomarker for the prognosis of early-stage disease screening. For instance, microbiome screening can be used to diagnose fatty liver disease. It is also used to predict treatment responses for many diseases, including cancer immunotherapy.
Microbiome epidemiologists are focused on developing suitable experimental designs, proper sample collection and data generation methods, and developing biobanks with a collection of microbes from various sources.
Microbiome Therapeutics
In contrast to genetic epidemiology, the microbiome is more amenable to modifications. Therefore, these have great potential for therapeutic applications. Microbiome therapeutics have evolved immensely with the development of fecal microbiota transplants (FMTs). In addition, live-cell therapies have exhibited significant health benefits, including the formulation of smart probiotics that contain engineered organisms and small-molecule drugs derived from or target the microbiome.
Microbiome therapeutics have been explored in a “bottom-up” manner by testing hypotheses using in vitro or in vivo experiments. However, “top-down” research can be conducted through observation-based studies. The progress of this sector requires the development of robust scientific consensus around reproducible methods and results from large-scale studies related to microbiomes.
Microbiome–drug interactions have been explored recently, which revealed that optimal drug dose between patients differs multifold due to variable microbial gut microbial composition. Notably, this could be a potential cause for the lack of or reduced positive response in drug trials.
Health Maintenance and Aging
The human microbiome is affected by every exposure, from prenatal to diet, and influences development, growth, and aging. Prenatal and early life exposures shape the infant microbiome and immune system, determining long-term health status. Owing to the knowledge of the importance of early life microbes, infant antibiotic usage, breastfeeding, exposure to allergens, and overall management of prenatal infectious disease episodes are given more weightage.
Healthy aging can be modulated by the microbiome, using diets, physical activity, immune maintenance, and therapeutics. Throughout life, nutrition and a healthy diet are the two most important factors in maintaining the human microbiome. At present, microbiome science lacks consensus regarding many aspects of diet and nutrition. The microbiome can modify the response to dietary intake.
Environmental Health
Microbiome science has also helped assess environmental health. The environmental microbiome has a dual function of biosensing and bioremediation. Recently, microbial communities have been considered as mediators of chemical toxicity. Chemical or drug exposure can change a healthy microbial community to a dysbiotic state.
Non-human microbial communities have a tremendous effect on human health. For instance, livestock microbial communities are potential targets for reducing methane emissions. Similar to that of humans, these microbes are used to mitigate animal diseases, maintain health, and enhance production.
Plant and soil microbes can be modified to improve production in agriculture. Compared to synthetic fertilizers and pesticides that impact the environment adversely, these microbes can enhance crop productivity without impacting the environment.
Microbiome Industry
At present, over 4,000 early-stage microbiome products have entered phase I-III clinical trials. These products are broadly classified as biomarkers for diagnostics or therapeutics. Most of these trials are conducted by early-stage companies under ten years of age. The Food and Drug Administration (FDA) has established clear regulations for live biotherapeutic products.
Before commercialization of a bioproduct, it is imperative to evaluate its efficacy, pharmacokinetics, safety, manufacturing, and route of delivery. Microbial applications are different in many ways from biological agents or small-molecule drugs.
Currently, another market is rapidly evolving around non-therapeutic, less-regulated health products. It is important to investigate microbial therapies at the population scale before implementation.
Next Steps
In the future, microbiomes can be used to improve personalized dietary responses. Formulating strategies to use the microbiome to obtain favorable responses effectively is important. In addition, there is a need to identify particular microbes or microbial metabolites that should be added or removed to enhance the response rate to cancer treatments (e.g., immunotherapy). Scientists are optimistic that completing the Human Microbiome Project will significantly benefit microbiome science.
Sources
- Taichi, A. et al. (2022) Codiversification of gut microbiota with humans. Science, 377 (6612), 1328 .DOI: 10.1126/science.abm7759
- Wilkinson, J.E. et al. (2021) A framework for microbiome science in public health. Nature Medicine, 27, pp. 766–774. https://doi.org/10.1038/s41591-021-01258-0
- Henry, L.P. et al. (2021) The microbiome extends host evolutionary potential. Nature Communications, 12, 5141 (2021). https://doi.org/10.1038/s41467-021-25315-x
- King, K. C. et al. (2020) Microbiome: Evolution in a World of Interaction. Current Biology, 30(6), pp. 265-267. https://doi.org/10.1016/j.cub.2020.02.010
- Valdes, M.A. et al. (2018) Role of the gut microbiota in nutrition and health. BMJ, 361. doi: https://doi.org/10.1136/bmj.k2179
- Davenport, E.R. et al. (2017) The human microbiome in evolution. BMC Biology, 15, 127. https://doi.org/10.1186/s12915-017-0454-7
Further Reading