Microbiome state of mind

Microbial ecosystems in soil, skin, stomachs, and space

By now you’ve likely been inundated with articles on “gut health” or seen “probiotic” marketing claims on many products (even outside the yogurts that seemly pioneered this tactic). This is driven by a growing scientific and cultural understanding of the importance of our personal “microbiome.” The emerging appreciation for the role of microbial communities has led to innovative applications in pharma, personalized nutrition, cosmetics, agronomics, food science, and possibly space colonization or cellular agriculture — which I explore below. This technology category coincides with a deep shift in the way we think about organisms, genomics, ecosystems, and industrial ecology.

You may recall the ad campaign with Jamie Lee Curtis promoting Danone’s Activia yogurt brand with claims of the probiotic “Bifidus regularis” and its benefits for bowel movement regularity.

What’s a microbiome?

Definitions

Microbiota are the communities of microorganisms (bacteria, fungi, viruses, etc) that live inside or intimately near multicellular “host” organisms (mammals, plants, corals, etc). “Microbiota” can be used interchangeably with “microbiome,” though the latter often more precisely refers to the genes of the microorganisms rather than as a whole. The relationship can be parasitic or neutral, but is often considered mutually beneficial (symbiotic), if understood at all. Nutrient processing+exchange is common. In the case of mutual interdepedence, we can think of a host and its microbiome as a single unit of life, which is called a “holobiont.”

Implications

Thinking of groups of organisms as a single unit is a mental leap from the agricultural monoculture, transactional economic, and other reductionist systems that seem to permeate from the scientific method and capitalism.

Now, companies are combining the microbiome brainstorm with industrial ecology to develop new products, production technologies, and marketing strategies. This has been called “industrial microbiomics”.

Note: I’m not talking about the (awesome) companies that are leveraging monocultural microbiology, designer organisms, and microbial fermentation like Ginkgo Bioworks, but rather a biotechnological approach to permaculture (productive community ecology). For example, Concerto Biosciences, based in Cambridge, MA, and founded in 2020 is building a platform around assembling “microbial ensembles” to biofertilize crops, treat disease, and more.

Applications

GutTech: Probiotics & Personalized Nutrition

Human bodies are unable to create or absorb many necessary nutrients, particularly proteins, directly. Instead, we, and most other eukaryotes, rely on microbes to convert what’s available into what we need. The ruminant (e.g. cow, goat) stomach microbiome is well known for its indispensable role in converting cellulose (grass) into usable proteins and fats.

We are in the midst of an intestinal microbiome trend, where people increasingly appreciate the role of the trillions of microbes for digestion, immunity, and even mood. Experts have moved beyond simple probiotics (supplements to promote the growth of beneficial gut microbes) and are applying bioinformatics to create a new wave of personalized nutrition. Companies including DayTwo, Nylos, and Biovis can analyze a persons ability to uptake nutrients based on stool sample and make diet recommendations for optimization of parameters like blood sugar level stability.

Medicine

Most of the activity has, however, been in healthcare. There are at least 28 medical startups focused on an array of microbiome applications. Most common is biopharmaceuticals like treatments for gastrointestinal microbiotic imbalance (obviously), CNS issues, UTIs, or infertility. Most work by modulating the microbiome to influence the rest of the body, like NASDAQ-listed Kaleido BioSciences. In essence, probiotics over antibiotics!

Microgenesis has successfully used gut and vaginal swabs to recommend neutraceutical and dietary changes to enhance the “fertility biome” and help women become pregnant. Brightcure helps the body combat UTI’s with a urogenital cream that kills “bad bacteria” and a supplement that introduces a strain of “good bacteria”. ZBiotics sells drinks with GM bacteria that help the gut microbiome better break down acetaldehyde and reduces hangovers after drinking.

Cosmetics

Like lower intestines, skin is an organ teeming with microbes with functions we are just beginning to understand and manipulate. Bacteria in toad skin microbiomes have been shown to fend against deadly fungi infections, for example. When it comes to humans, we love our skin and cosmetics is naturally the first place applications were developed. AOBiome is developing probiotics of Nitrosomonas eutropha bacteria aimed at reinvigorating the natural skin microbiome sterilized by modern use of antibiotics, soaps, and shampoos. Cybele has developed a direct-to-consumer brand of topical serums that trigger skin microbes to produce beneficial compounds like moisturizers and eventually scents, insect repellants, and more.

Soil: Agronomics and Bioremediation

Plants and the soils surrounding their roots are an especially promising area for microbiome research and commercialization. As we learned more about agriculture, we’ve realized that repeated monocropping, soil-tilling, and chemical fertizilation is inefficient and unsustainable. Bioferilizers have emerged to support beneficial soil microganisms and mycorrhizal (fungal) networks, like Reazent and MycoBloom, that increase yields and soil health.

Effective bioremedation of depleted or contaminated soils is also possible. Rather than hauling off soil from superfund sites or brownfields (or, the American Way, ignoring the problem), we can restore the soil. Allied Microbiota has developed a bacteria that feeds on chemicals like petroleum and chlorine, allowing for an easier solution for cleanup. Evenually, we’ll get even more precise and comprehensive thanks to technologies like soil-microbiome testing robots and more microbiota research. Perhaps an understanding of the ocean microbiome can also let us develop biological oil spill clean up like fungi-based solutions proposed by mycologist Paul Stamets (rather than using petrochemical dispersants).

Space, Food, & Other Speculative Uses

I believe we are at the very beginning of leveraing industrial microbiomics. Humans have used fermentation – the use of microbes to process food like cheese, beer, kimchi, sourdough, and tempeh – for millennia. This was often without an understanding of how the native microbiomes on the food were working. There are immense opportunities to combine traditional fermentation with bioinformatics, industrial ecology, and microbiomics to transform the food system, highlighted in the Good Food Institute’s Fermentation State of the Industry report.

One far-flung impact of microbiomics is the ability to create closed-loop (circular) biological systems. The input of a host organism may match the outputs of the microbiome, etc. This concept is growing in popularity due to sustainability benefits, but I imagine it’ll be even bigger in the vacuum of space, when all systems must be closed loop. We will need a deep understanding of how microbiomes work and how they can be leveraged. Maybe we will have fermentation with “microbial permacultures” where we use communities of microbes to produce the protein, vitamins, enzymes, and other molecules that we need with minimal inputs.

Last thought

I think that the microbiome mindset will prove valuable for expanding how we think about systems and technology. One concept I keep thinking about is our “technobiome” – the technologies we affix to ourselves like clothing, glasses, cosmetics, watches, cell phones, vitamins, and more. Maybe us and our many intimate technolgies are already a holobiont. How will this change as we continue to master biotechnologies and nanotechnologies?

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Sources
Margulis, Lynn; Fester, René (1991). "Symbiosis as a Source of Evolutionary Innovation". MIT Press. ISBN9780262132695.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944797/
https://apnews.com/article/a7b70f21b6c75f95210112390cc813ad
https://www.frontiersin.org/articles/10.3389/fgene.2019.00721/full
https://www.marineinsight.com/environment/10-methods-for-oil-spill-cleanup-at-sea/
IndieBio accelerator appears to be the leading investor in this space, with numerous companies mentioned above in their portfolio.