Did you know that an autoimmune disease now affects one in five Americans? Of these, 80% are women; autoimmune disease is the fifth leading cause of death in women under 65. Most autoimmune diseases are being diagnosed in increasing numbers, but it is still unclear if all this variance is due to higher awareness, medical literacy, or better diagnosis techniques.

The effects of autoimmune diseases can be devastating. As a person’s immune system attacks their body instead of microbes or cancerous cells, they can experience chronic fatigue, chronic pain, drug dependency, depression, and social isolation. These symptoms annihilate mental health, wreck promising careers, destroy lives, and, often, financially ruin families. For too many, these illnesses result in early death.

The Missing Friends

The Old Friends Hypothesis suggests that early and regular exposure to harmless microorganisms—"old friends" present throughout human evolution and recognized by the human immune system—train the immune system to react appropriately to threats.

Here's the problem: some very specific microbes that we've coevolved with—for potentially millions of years (considering monkeys emerged 35 million years ago)—are no longer in our gut. Those are literally gone; they cannot be replaced by eating fiber, kefir, or any probiotics on the market. And this might be the reason the immune system of many people is dysfunctional—it's missing organisms it's been interacting with for a very long time.

We know this precisely because we've been able to compare the microbiome of industrialized populations with modern hunter-gatherers, who possibly have the microbiome closest to early humans. The Hadza, a protected hunter-gatherer Tanzanian indigenous ethnic group, are known for having the highest gut diversity of every population. The Hadza had an average of 730 species of gut microbes per person. The average Californian gut microbiome contained just 277 species, and the Nepali microbiome fell in between. Ultra-deep sequencing of the Hadza microbiome reveals 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. The researchers identified 124 gut-resident species absent or vanishing in industrialized populations.

As seen in the above picture, there is, at the same time, reduced diversity and an entirely different type of microbial ecology in our gut. Sonnenburg & Sonnenburg list five major reasons that could mediate this change: (1) consumption of highly processed foods; (2) high rates of antibiotic administration; (3) birth via cesarean section and use of baby formula; (4) sanitation of the living environment; and (5) reduced physical contact with animals and soil.

The question that interests me here is, of course: what would happen if we were to reintroduce these "lost" microbes into our bodies? Well, we have no idea! Worse, currently, as of 2024, aside from Symbiome, who focuses on skin, I am not aware of any initiative by a private company or group to develop any treatment based on the ancestral microbiome. Most previous projects seem to have been shelved. However, private, secret initiatives may be happening at the moment; after all, harvesting the microbiome of hunter-gatherers is not without controversies.

However, given what we've learned about the microbiome in the last decades and its connection to just about every biological process, I do believe rewilding the gut might be the most effective public health initiative of the 21st century:

• The cost and suffering caused by autoimmune conditions are massive and will increase in the future. Chronic conditions use most of the resources of public health care systems.
• Rewilding the gut might be far more effective, cheaper, and durable than any pharmaceutical treatment for all the aforementioned diseases.
• Rewilding the microbiome might have large-scale positive impacts on health; it might cure specific diseases and also improve general health (mood, metabolism, life expectancy, inflammation control, or even aging).
• Developing countries are not invulnerable to autoimmune diseases. We are observing the rise of autoimmune diseases or allergies in poorer countries, which is most likely linked to antibiotic use, urbanization, processed food, and better hygiene practices.

How do we rewild the modern gut, then?

As of now, my favored approach would be to distribute ancestral bacteria as 'ancestral probiotics.' Working with microbiome researchers, we would analyze the gut-resident species across various populations of hunter-gatherers, chimpanzees, and bonobo populations, and identify common species. A species found in 1) wild primates, 2) multiple hunter-gatherer populations, and 3) absent from industrialized populations, would make a very strong candidate for a microbe that probably belongs in our gut.

Once some species have been identified, they could be cultured and analyzed further, then tested. Once we have something (years later), it could be licensed to probiotics companies or sold online.

I would be ready to inoculate myself with any bacteria that fit these three criteria.

Why am I writing this?

I'm interested in working on this very problem,  and I'd like to hear ideas, suggestions, and criticisms. I have listed an approach, but there are certainly other ways to reach these goals.

Finally, if you are interested in this topic, send me a PM. I'll be happy to discuss further!