I Contain Multitudes

1. Microbes: Invisible Architects of Life

“We exist in symbiosis – a wonderful term that refers to different organisms living together.”

Ubiquitous and ancient. Microbes, including bacteria, archaea, fungi, and viruses, are the oldest and most abundant forms of life on Earth. They have shaped the planet's atmosphere, drive essential nutrient cycles, and are integral to the lives of all animals. They are not just "germs" but essential partners.

• Microbes were the sole inhabitants of Earth for billions of years.
• They were the first to photosynthesize, releasing oxygen into the atmosphere.
• They drive planetary cycles of carbon, nitrogen, sulfur, and phosphorus.

More than just passengers. Microbes are not merely hitchhikers on our bodies; they are active participants in our biology. They live on our skin, in our guts, and even inside our cells, forming complex communities that influence our health, development, and behavior.

• The human body contains roughly the same number of microbial cells as human cells.
• Microbes collectively wield 500 times more genes than our own cells.
• They are a hidden organ, as important as a stomach or an eye.

A new perspective. Understanding microbes requires a shift in perspective, from viewing them as enemies to appreciating them as essential partners. This new view of life is a more complete and accurate one.

• We are not individuals but multi-species collectives.
• We are never truly alone, even when we are alone.
• We are all zoos in our own right.

2. Symbiosis: A Spectrum of Partnerships

“Every symbiosis is, in its degree, underlain with hostility, and only by proper regulation and often elaborate adjustment can the state of mutual benefit be maintained.”

Beyond simple labels. Symbiosis, the term for different organisms living together, encompasses a wide range of relationships, from mutualism (both benefit) to parasitism (one benefits at the expense of the other). These are not fixed categories, but rather points on a spectrum.

• A microbe can be a mutualist in one context and a parasite in another.
• Even beneficial microbes can create vulnerabilities that other pathogens exploit.
• The same molecules can trigger both inflammation and development.

Conflict and cooperation. Symbiotic relationships are not always harmonious. Even in mutualistic partnerships, there is often an underlying tension, with each partner seeking to maximize its own benefit.

• Microbes have their own interests, which may clash with those of their hosts.
• Hosts must constantly regulate their microbes to maintain a beneficial partnership.
• Cheating and betrayal are always a possibility.

Dynamic relationships. Symbioses are not static; they are constantly evolving and changing. The balance between cooperation and conflict is a dynamic one, shaped by the environment, the host, and the microbes themselves.

• Microbes can switch roles depending on the context.
• Partnerships can break down if the balance is disrupted.
• The same microbes can be good in one place and bad in another.

3. Microbes as Body Builders: Shaping Development

“The results of these studies are the first experimental data demonstrating that a specific bacterial symbiont can play an inductive role in animal development.”

Microbes as architects. Microbes are not just passengers; they are active participants in the development of animal bodies. They release molecules that trigger changes in host genes, shaping the growth of organs and tissues.

• The bobtail squid's light organ develops properly only in the presence of specific bacteria.
• Germ-free animals, raised without microbes, have abnormal guts and immune systems.
• Microbes are not just a part of our ecology, but also a part of our development.

Co-development. Animal development is not a self-contained process; it is a conversation between the host and its microbes. The host's genes provide the basic blueprint, but the microbes provide the cues and signals that guide the process.

• Microbes release molecules that steer the growth of organs.
• They educate the immune system, teaching it to tell friend from foe.
• They affect the development of the nervous system.

Ancient interactions. The influence of microbes on animal development is an ancient phenomenon, dating back to the origins of the animal kingdom. The first animals evolved in a world teeming with microbes, and they have been shaped by those interactions ever since.

• Choanoflagellates, the closest living relatives of animals, form colonies in response to bacterial signals.
• Marine larvae settle down and transform into adults when they encounter specific bacteria.
• Microbes are not just unavoidable; they are useful.

4. The Gut-Brain Axis: Microbial Influence on Mind

“Our lives are heavily influenced by external forces that are actually inside us, by trillions of things that are separate from us and yet very much a part of us.”

Two-way communication. The gut and the brain are connected by a complex network of nerves, hormones, and immune cells, collectively known as the gut-brain axis. This is a two-way street: the brain can affect the gut, and the gut can affect the brain.

• Stress can change the gut microbiome.
• Gut microbes can affect the brain’s chemistry.
• The gut-brain axis is a physical embodiment of the connection between our bodies and our microbes.

Microbes and behavior. Gut microbes can influence our behavior, including our social attitudes, our ability to deal with stress, and even our food cravings.

• Mice with altered gut microbes show signs of anxiety, repetitive movements, and social problems.
• Probiotics can reduce anxiety and depression in mice.
• Gut microbes may manipulate our food cravings by releasing chemicals that affect our brains.

A new view of self. The influence of microbes on our brains challenges our traditional notions of individuality, free will, and identity. We are not just individuals, but complex ecosystems, shaped by forces both inside and outside of our bodies.

• Our microbiomes can be very different, even if our genomes are similar.
• Perhaps it is less that I contain multitudes and more that I am multitudes.
• Microbes subvert our notions of individuality.

5. Microbial Biogeography: Islands Within

“To microbes, every host is effectively an island – a world surrounded by void.”

Microbial landscapes. Just as the Earth has different ecosystems, so too does the human body. Each body part – skin, mouth, gut, genitals – has its own characteristic community of microbes.

• The skin microbiome is the domain of Propionibacterium, Corynebacterium, and Staphylococcus.
• Bacteroides lords over the gut.
• Lactobacillus dominates the vagina.
• Streptococcus rules the mouth.

Individual archipelagos. Each person is more like an archipelago – a chain of islands – than a single landmass. The microbes on your forearm are more similar to those on my forearm than to those in your mouth.

• The variations between body parts dwarf those between people.
• Even your right and left hands share just a sixth of their microbial species.
• Each organ is also variable in itself.

Dynamic communities. The microbiome is not static; it changes over time, from birth to old age. It is shaped by our genes, our environment, our diet, and our experiences.

• A baby's microbiome is initially colonized by its mother's vaginal microbes.
• The gut microbiome becomes more diverse as a baby picks up new species from its parents and environment.
• The microbiome may vary from day to day, from sunrise to sunset, or even from meal to meal.

6. The Hygiene Hypothesis: A Modern Imbalance

“The history of warfare always proves more glamorous than accounts of cooperation.”

The rise of modern plagues. Many conditions, including obesity, asthma, colon cancer, diabetes, and autism, are accompanied by changes in the microbiome, suggesting that these microbes are at the very least a sign of illness, and at most a cause of it.

• These conditions have become more common in the last half-century.
• They are often accompanied by changes in the microbiome.
• They are health problems re-envisioned as ecological ones.

The hygiene hypothesis. The hygiene hypothesis suggests that our modern lifestyles, with their emphasis on sanitation and cleanliness, have reduced our exposure to microbes, leading to an imbalance in our immune systems.

• We have become a nation of tubbed, scrubbed, deodorized neurotics.
• Our immune systems are now more likely to overreact to harmless substances.
• We have become more prone to allergies, asthma, and autoimmune diseases.

The loss of old friends. The microbes that we have lost are not just pathogens; they are also our “old friends” – the species that have coevolved with us for millennia and that play a crucial role in shaping our immune systems.

• We have become more distant from livestock, pets, and other animals.
• We have become more reliant on antibiotics and antibacterial products.
• We have become less exposed to the microbes in soil, water, and air.

7. Dysbiosis: When Microbial Communities Go Wrong

“The germ-free animal is, by and large, a miserable creature, seeming at nearly every point to require an artificial substitute for the germs he lacks.”

Microbial imbalance. Dysbiosis refers to a state of microbial imbalance, where the composition and function of a microbial community have shifted into an unhealthy state. It is not about the presence of a single pathogen, but about the disruption of an entire ecosystem.

• Dysbiosis is a state of imbalance and discord.
• It is the dark reflection of symbiosis.
• It is disease, recast as an ecological problem.

The cycle of disease. Dysbiosis can be both a cause and a consequence of disease. It can be triggered by a variety of factors, including diet, antibiotics, stress, and genetic predispositions.

• Dysbiosis can lead to inflammation, which can damage tissues and organs.
• It can make us more vulnerable to infections.
• It can interfere with our ability to digest food and absorb nutrients.

A complex problem. Dysbiosis is not a simple problem with a simple solution. It is a complex, multifaceted issue that requires a holistic approach.

• There is no single “healthy” microbiome.
• The same microbes can have different effects in different contexts.
• We need to understand the interactions between microbes and their hosts to restore balance.

8. Microbial Manipulation: Restoring Balance

“We need to separate important from harmonious. The microbiome is incredibly important but it doesn’t mean that it’s harmonious.”

Beyond antibiotics. The traditional approach to treating microbial diseases has been to kill the pathogens with antibiotics. But this approach is often ineffective and can even make things worse by disrupting the microbiome.

• Antibiotics are shock-and-awe weapons that kill both good and bad bacteria.
• They can lead to the rise of antibiotic-resistant bacteria.
• They can disrupt the microbiome, making us more vulnerable to disease.

Probiotics and prebiotics. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Prebiotics are substances that selectively nourish beneficial microbes.

• Probiotics can help to restore balance to the microbiome.
• Prebiotics can help to feed and support beneficial microbes.
• But they are not a panacea.

Fecal transplants. Fecal microbiota transplants (FMT) involve transferring stool from a healthy donor to a sick patient. This technique has shown remarkable success in treating C. difficile infections, but its effectiveness for other conditions is still unclear.

• FMT is a way of resetting the entire gut ecosystem.
• It is a powerful tool, but it is not without risks.
• It is a stopgap, not a long-term solution.

A new era of medicine. The future of medicine will involve a more nuanced approach to the microbiome, one that focuses on restoring balance rather than simply killing microbes.

• We will need to develop personalized treatments that are tailored to each individual’s unique microbiome.
• We will need to use a combination of probiotics, prebiotics, and other strategies to manipulate the microbiome.
• We will need to view the microbiome as an essential organ, as important as a stomach or an eye.

9. Horizontal Gene Transfer: Microbial Innovation

“Every species has come into existence coincident both in space and time with a pre-existing closely allied species.”

Microbial promiscuity. Bacteria can exchange DNA with each other through a process called horizontal gene transfer (HGT). This allows them to rapidly acquire new abilities, including the ability to digest new foods, resist antibiotics, and infect new hosts.

• Bacteria can swap genes as easily as we might exchange phone numbers.
• They can scrounge up discarded bits of DNA in their environment.
• They can rely on viruses to move genes from one cell to another.

Accelerated evolution. HGT allows bacteria to evolve at blistering speeds, adapting to new challenges in a matter of days or weeks rather than millennia.

• It allows them to acquire new traits wholesale.
• It can transform harmless microbes into deadly pathogens.
• It can turn vulnerable pathogens into antibiotic-resistant superbugs.

Animal innovation. Animals can also acquire new abilities through HGT, by picking up genes from their microbial partners.

• The spider mite has a bacterial gene that allows it to detoxify cyanide.
• The coffee berry borer beetle has a bacterial gene that allows it to digest caffeine.
• Braconid wasps have domesticated viruses that help them to parasitize caterpillars.

A new view of evolution. HGT challenges our traditional view of evolution, which focuses on the slow and steady accumulation of mutations within a single species. It shows that evolution can also be a rapid and collaborative process, where genes can jump between different species.

• HGT is a way of accelerating evolution.
• It allows animals to tap into the vast genetic resources of the microbial world.
• It is a reminder that evolution is not just about competition, but also about cooperation.

10. The Holobiont: A Unified View of Life

“From the elephant to the butyric acid bacterium – it is all the same!”

Beyond the individual. The concept of the holobiont suggests that we should view animals not as isolated individuals, but as complex communities of interacting organisms, including their microbes.

• A holobiont is a collection of organisms that spend significant parts of their lives together.
• It is a unified entity, where the fates of the host and its microbes are intertwined.
• It is a more accurate representation of the natural world.

The hologenome. The hologenome is the total collection of genes in a holobiont, including both the host’s genes and those of its microbes. It is the unit of natural selection in evolution.

• The hologenome is a way of thinking about evolution that includes microbes.
• It recognizes that microbes are not just passengers, but active participants in evolution.
• It emphasizes the importance of symbiosis in shaping the diversity of life.

A new perspective on life. The holobiont concept challenges our traditional notions of individuality and identity. It suggests that we are not just individuals, but complex ecosystems, shaped by the interactions between our genes and those of our microbes.

• We are all part of a larger web of life.
• We are all connected to each other through our microbes.
• We are all part of a single, unified world.

Last updated: January 25, 2025