The Microbial Age

A new era is coming and it will change everything.

So far, humanity has experienced three distinct eras: the Agricultural Age, the Industrial Age and, most recently, the Information Age, which is characterized primarily by communication technology and rapid information processing. Some experts predict that the next epoch will be the Age of Artificial Intelligence.

I disagree.

We are on the verge of entering the Microbial Age.

From the Information Age to the Microbial Age

The Agricultural Age lasted from around 10,000 BC until the mid-18th century, when the Industrial Age began. The current Information Age commenced in the middle of the 20th century and can be divided into an electronic age (from the mid-20th century) and a digital age (beginning in the 1980s/90s and continuing to the present).

“The development of full artificial intelligence could spell the end of the human race.”

The digital age is defined by pervasive digitization, connectivity, the data economy and, increasingly, artificial intelligence. Humanity has undergone more rapid transformation in less than 100 years than in any previous era. Many believe that this pace of change will accelerate in the Age of Artificial Intelligence. However, this is not without risk. AI's potential to destroy humanity is greater than its potential to save it. As Stephen Hawking stated in a BBC interview in 2014:

“The development of full artificial intelligence could spell the end of the human race. It would take off on its own and redesign itself at an ever-increasing rate”.

Alongside the growing dominance of AI, another process is unfolding that has received too little attention thus far. It concerns our symbiosis with microorganisms. This partnership, which dates back many thousands of years, is beginning to dissolve.

Recent research has shown with a high degree of certainty that many civilization diseases, such as neurodegenerative disorders, cancer, type 2 diabetes and pathological obesity, are at least partially caused by the ongoing breakdown of our microbiome.

The Holobiont in Free Fall

Humans are holobionts. Our 30 trillion human cells interact closely with approximately 39 trillion bacteria (1). These microbial populations constantly adapt to us and have coevolved with us. We know that microbial diversity has dramatically decreased, and populations have shifted so much that a natural balance can often no longer be restored. This is significant because the human microbiome relies on continuous adaptation and renewal.

Studies have shown that certain bacterial species have become extinct or are on the verge of extinction. An analysis of up to 2,000-year-old stool samples showed that the human gut ecosystem has lost many species and has become significantly less diverse (2).

“We reach a tipping point, and the human holobiont ceases to function.”

Our microbiome contains specific key taxa, the eradication of which will have unpredictable consequences. There are also microbial guilds that fulfill specific functions in our microbiome and are essential for our survival. If both disappear, we reach a tipping point, and the human holobiont ceases to function (3).

Technology vs. Nature

This fact has given rise to two movements that could hardly be more different. Both lay the foundation for a new Microbial Age but approach the issue from opposite sides.

The first group believes that progress in microbiome analysis, microbial engineering, and designing a new microbiome is advancing so rapidly and efficiently with the help of AI that only putting this research into practice can ensure our survival.

The second group, on the other hand, believes that technological progress will deteriorate the microbiome rather than improve it.

The Limits of Technology

Let's examine the efforts of the first group. When we consider what we truly know about microbial populations today—their abundance, location, and symbioses—we must admit, in true Socratic tradition, that we know nothing.

Are we really going to use, for example, CRISPR to change or create bacteria that play a crucial role in our bodies? CRISPR is the molecular equivalent of “Ctrl+F” for searching and “Ctrl+X/Ctrl+V” for cutting and pasting in the genome—a tool we borrowed from bacteria (4). Or any other methods that directly change our microbial populations?

This assumption is, to put it mildly, very bold. Currently, we have only a vague understanding of which bacteria in the body are important, let alone their functions. We usually don't know exactly where they reside in the gut or what associations they form with other populations. Most studies are actually based on fecal samples. Localization studies are rare.

“Attempting to "tailor" microbial populations with our current understanding would be disastrous.”

Furthermore, we are increasingly realizing that each individual possesses a unique microbiome. There is no "blueprint" that applies to everyone. This complicates analysis and makes "optimizing" or "repairing" the microbiome virtually impossible.

Everyone is different, with different habits, environments, and people around them. Although recurring bacterial groups are found in the microbiome, it would be presumptuous to claim that we know how the microbiome is structured.

Attempting to "tailor" microbial populations with our current understanding would be disastrous because no one knows what any individual's microbiome should look like. Intervening at this stage is like playing God without any real knowledge.

A Frosted-Glass View

Of course, many studies have been conducted on the microbiome. However, most are based on a fundamental error. They assume that what is sequenced accurately reflects reality in terms of identity and quantity. But this is a fundamentally flawed assumption.

Despite enormous data volumes, conventional sequencing strategies deliver a distorted image of the microbiome.

First, 16S amplicon sequencing misses relevant taxa and cannot reliably quantify: primer bias and varying rRNA gene copy numbers mean entire lineages remain virtually invisible, and abundance estimates are inaccurate.

Second, short-read shotgun protocols stack fragments of just a few hundred bases. When diversity is high, genome puzzles cannot be assembled accurately. Quantification becomes estimation with logarithmic error. Even with modern long-read sequencing platforms, organisms slip through the cracks because cell lysis remains the bottleneck (5).

Third, the spatial dimension is almost always absent; we rarely know where an organism sits in the gut or with whom it physically interacts. This is exactly where fluorescence in situ hybridization comes in. It maps bacteria at the micrometer scale but remains underutilized.

Despite better methods, our view of the microbiome remains like looking through frosted glass—helpful, but far from an exact picture of reality.

If we try to intervene and reshape microbial populations now, we are embarking on a journey into the unknown—and potentially disaster.

Back to Nature and Its Challenges

On the other hand, there is a second group that is convinced our manipulations will only make things worse and that we should refrain from such interventions. They believe that the loss of microbial diversity can be stopped —and even reversed— not through genetic engineering, but through acknowledging the damage caused by industrialization. A "back to nature" approach. Whether this path is feasible, however, is doubtful. Because:

1. The corporations in the food industry are massive global players focused primarily on shareholder value. Radical rethinking seems unlikely.

2. Politics has already ceased to serve the people for years, showing increasingly disturbing tendencies toward power that contradict societal responsibility. This became especially clear during the Corona years.

3. A rapidly growing global population must be fed and housed.

Given these circumstances, it is difficult to believe that a natural return to a diverse microbiome is realistic.

Strauss-Howe for Microorganisms

So, what will the microbial age look like?

It is likely that neither group will prevail, and a middle path will have to be found. Whether this compromise is the best solution is doubtful. Most likely, things will continue as they are until a catastrophe forces a new beginning. This may sound dystopian, but, in light of human history, it is probably the most realistic scenario.

The "Strauss-Howe model of the four turnings," described by U.S. historians William Strauss and Neil Howe, lays out an 80–90-year societal cycle divided into four phases: High, Awakening, Unraveling, and Crisis. Though designed to describe large-scale societal changes occurring in "waves," the model applies quite well to the development of the human microbiome—albeit on a different timescale.

In the first phase, the High, the microbiome was balanced, diverse, and stable. Plagues often decimated large swathes of humanity, but this was not an evolutionary disadvantage. World population levels were kept in check for the planet. When too many people congregated in close quarters, outbreaks of infectious diseases due to poor hygiene reduced population density to a tolerable level again.

In the second phase, the Awakening, major plagues were held at bay by antibiotics. The increasing world population could still be fed thanks to the achievements of industrialization. At this point, the original natural microbiome ended and diversity began to decline continuously.

In the third phase, the Microbial Age that is now beginning, it is recognized that the holobiont human must be preserved if we want to survive. People will be full of hope. But this will spark the first conflicts between the two aforementioned groups. While the first group pursues the technological, AI-driven optimization of the microbiome, the second group turns to the "back to nature" movement. They believe that the microbiome can regenerate itself if a path back to a more natural environment is found.

The ideologies of both groups are irreconcilable. This will lead to increased worldwide tension and a lack of solutions. And that will be the real problem. It will be a "stuck state." Because we are unable to act, we will face the inevitable.

Therefore, in the fourth phase, the Crisis Phase, a "black swan" event will occur: a massive global shock. This event could be a natural disaster, a microbiome breakdown, nuclear war, or an unprecedented pandemic. This catastrophe will decimate the Earth's population.

Afterwards, a very long phase of adaptation will follow. It will last decades, centuries or even thousands of years. During this time, people will adapt to the new conditions, and the destroyed microbiome will have time to reassemble itself.

Then, the High phase will begin again, and the cycle will repeat.

In this scenario, it becomes clear that the temporal scales defined by Strauss and Howe do not apply. While those historians envisioned 20-year rhythms based on generational logic, where new cohorts rise to leadership and define the spirit of the times, the microbial timescale is much longer.

At first glance, this perspective might appear to be dystopian and even somewhat depressive. However, it is rooted in the fundamental biological principles.

The Bacterial Growth Curve

For example, bacteria have a growth curve consisting of four phases: an adaptation phase, where they acclimate to new nutrient conditions; an exponential growth phase; a stationary phase, where further growth is impossible; and a death or dying phase, where depleted nutrients and accumulating toxins lead to the demise of the entire population.

Unlike a Petri dish, which is a closed system with no escape for the bacteria, planet Earth—with photosynthesis sustained by the sun—is a more or less open system. Thus, after phase four, phase one can start again.

It is a biological cycle. In the context of thousands of years, this is the most realistic scenario.

The True Microbial Age

However, if a global catastrophe results in conditions toxic to humans, such as an oxygen-depleted atmosphere or reduced CO₂ levels below 150 ppm, where all plant growth becomes impossible, or a permanently broken holobiont, then the human cycle will end.

The brilliant symbiosis of eukaryotic and prokaryotic cells will cease to exist, remaining little more than a fleeting moment in history.

Instead, the true microbial age will begin in a new dimension: bacteria growing freely, without human constraints.

For us humans who will have disappeared by then, the quote from the great French scientist Louis Pasteur will have come true:

"Messieurs, c'est les microbes qui auront le dernier mot!"
Gentlemen, it is the microbes who will have the last word.

Sources and further readings:

(1) Sender R., Fuchs S., Milo R. (2016). “Revised estimates for the number of human and bacteria cells in the body.” PLOS Biology 14 (8): e1002533. DOI: 10.1371/journal.pbio.1002533.

(2) Wibowo, M.C., Yang, Z., Borry, M. et al. “Reconstruction of ancient microbial genomes from the human gut.” Nature 594, 234–239 (2021). https://doi.org/10.1038/s41586-021-03532-0

(3) Larsen O and van de Burgwal L (2021) On the Verge of a Catastrophic Collapse? “The Need for a Multi-Ecosystem Approach to Microbiome Studies.” Front. Microbiol. 12:784797 doi: 10.3389/fmicb.2021.784797

(4) Doudna, J. A. & Charpentier, E. (2014). “Genome editing: The new frontier of genome engineering with CRISPR-Cas9.” Science, 346 (6213): 1258096. https://doi.org/10.1126/science.1258096

(5) Amarasinghe SL, Su S, Dong X, Zappia L, Ritchie ME, Gouil Q (2020). “Opportunities and challenges in long-read sequencing data analysis.” Genome Biology 21 (30). https://doi.org/10.1186/s13059-020-1935-5