Capítulo 1
The Invisible World Within and Around Us
When was the last time you considered that you are never truly alone? Right now, trillions of microscopic organisms are living on and inside your body, influencing everything from your immune system to your mood. This invisible world of microbes represents biology's most significant revolution since Darwin, transforming our understanding of life itself. Ed Yong's "I Contain Multitudes" takes readers on a fascinating journey through this microscopic realm, revealing how bacteria, archaea, fungi, and viruses shape all life on Earth. The book has garnered praise from scientists and general readers alike, with Bill Gates naming it one of his favorite books of 2016. As Yong eloquently demonstrates through countless examples-from glowing squid to disease-fighting wasps-we exist in a world of symbiosis where no organism is truly independent. We are all, as Walt Whitman wrote, large and containing multitudes.
Capítulo 2
The Microbial Revolution: Discovering Our Hidden Partners
For most of Earth's 4.54-billion-year history, microbes ruled alone. If Earth's timeline were compressed into a single calendar year, multicellular life would only appear in October, with humans showing up just 30 minutes before midnight on December 31st. During their long reign, microbes transformed our planet irrevocably-enriching soils, driving elemental cycles, inventing photosynthesis, and oxygenating our atmosphere.
The most profound symbiotic event in history occurred about two billion years ago when a bacterium merged with an archaeon (another single-celled organism), creating the first eukaryotic cell. This improbable union, which happened only once in four billion years, gave rise to all complex life as the bacterium eventually became mitochondria, providing energy that allowed for larger, more complex cells.
After eukaryotic cells evolved, some began clustering together into multicellular creatures like animals and plants. These larger organisms became living islands hosting vast microbial communities. While it's often claimed humans contain ten microbial cells for every human one, recent estimates suggest a roughly even split-about 30 trillion human cells and 39 trillion microbial ones.
Most microbes aren't the disease-causing pathogens we fear. Of thousands of bacterial species in our bodies, fewer than 100 cause human diseases. The rest form a hidden organ-our microbiome-with genetic wealth 500 times greater than our own genome. They digest our food, produce vitamins, break down toxins, protect us from pathogens, guide our bodily development, educate our immune system, and even influence our behavior.
Beyond humans, microbes have bestowed extraordinary powers on countless animals: hoopoes paint their eggs with antibiotic-secreting bacteria; leafcutter ants carry microbes that protect their fungal gardens; pufferfish use bacteria to produce lethal toxins; and nematode worms kill insects by vomiting toxic glowing bacteria into their bodies.
Like the naturalists who once cataloged visible life, today's scientists are mapping the biogeography of microbes. To microbes, every host is an island, and each person has their own distinctive microbial community shaped by genetics, environment, diet, and experience. Different body regions host their own dominant microbial species-Propionibacterium rules the skin, Bacteroides the gut, Lactobacillus the vagina, and Streptococcus the mouth.
The microbiome changes over time, too. Newborns acquire their mother's vaginal microbes at birth, with almost three-quarters of a baby's strains tracing directly to its mother. The infant microbiome then undergoes a predictable succession as the baby encounters new species, taking one to three years to reach a relatively stable adult state.
This field has exploded in recent years as we've realized microbes profoundly affect our health-influencing vaccine responses, nutrient extraction, cancer treatment outcomes, and conditions like obesity, asthma, and autism. When viewed through a microbial lens, even familiar aspects of animal life take on new wonder-from a hyena marking territory with microbially-produced scents to a mother building microbial worlds in her nursing infant's gut.
Capítulo 3
Pioneers Who Unveiled the Microbial World
Carl Woese revolutionized biology in the 1970s by analyzing 16S rRNA, a universal molecule found in all organisms. When examining a methane-producing microbe from sewage sludge, he made a stunning discovery: this organism wasn't a bacterium at all but belonged to a completely separate domain of life. In 1977, Woese published his revolutionary finding, introducing a third domain-the archaebacteria (later renamed archaea)-distinct from bacteria and eukaryotes.
Despite fierce criticism that earned him the nickname "microbiology's scarred evolutionary," Woese's work proved correct and transformed biology by establishing gene comparison as a fundamental method for determining evolutionary relationships. Norman Pace extended Woese's approach in the 1980s by extracting DNA directly from environmental samples without growing the microbes first. Starting with Yellowstone's Octopus Spring, Pace pulled genetic material from scalding water and identified two bacteria and an archaeon-all new to science.
By 1991, Pace and student Ed DeLong found 15 new bacterial species in Pacific Ocean plankton. The bacterial tree of life exploded from about 12 major groups (phyla) in the 1980s to around 100 today-with about 80 never cultured in laboratories. This culture-free approach evolved into metagenomics-sequencing all microbial genes in environmental samples-which Jo Handelsman called "the most important event in microbiology since the invention of the microscope."
David Relman, initially frustrated by normal microbiota contaminating his pathogen samples, realized these residents deserved study. Analyzing his own dental plaque, he found far more bacterial diversity than previous culture methods had revealed. In 2005, he identified nearly 400 species in human intestines-80% new to science.
By the early 2000s, researchers were conducting sequencing surveys throughout the human body. Jeff Gordon showed that gut microbes control fat storage and blood vessel creation, and that obese people have different microbiomes than lean individuals. The human microbiome, long championed by scientific rebels, had finally entered the mainstream.
This transformation is celebrated at Micropia, the world's first microbe museum, which opened in Amsterdam in 2014. Fittingly located just 40 miles from Delft where Leeuwenhoek first observed bacteria, the museum features a replica of his microscope alongside modern displays. After 350 years of growing knowledge, microbes are no longer neglected B-listers or villains but fascinating stars worthy of attention.
Capítulo 4
Architects of Life: How Microbes Build Animal Bodies
The Hawaiian bobtail squid's remarkable ability to hide from predators by eliminating its shadow comes from luminous bacteria called Vibrio fischeri housed in light organs on its underside. These bacteria produce a downward glow that matches moonlight penetrating from above, effectively canceling out the squid's silhouette. But the relationship goes beyond camouflage-these bacteria actually help build the squid's body.
Margaret McFall-Ngai has studied this partnership for nearly three decades, discovering that when just five V. fischeri cells make contact with a newly hatched squid, they activate genes that produce antimicrobials harmful to other bacteria but not to themselves. The bacteria then move inward through pores to reach crypts where they trigger physical changes in the squid's tissues. The entrance narrows, ensuring no other microbes can enter. McFall-Ngai's groundbreaking discovery was that "a specific bacterial symbiont can play an inductive role in animal development"-in other words, microbes sculpt animal bodies.
This phenomenon extends far beyond squid. Scientists raising germ-free animals find they survive but are compromised-particularly in gut development, where microbes like Bacteroides thetaiotaomicron activate host genes for nutrient absorption, barrier formation, and blood vessel development. Animals evolved in a microbe-dominated world, making these partnerships inevitable and advantageous.
Nicole King studies choanoflagellates ("choanos"), single-celled aquatic predators that are the closest living relatives to animals. Her favored species, Salpingoeca rosetta, sometimes forms colonies when exposed to specific bacterial signals. Graduate student Rosie Alegado identified Algoriphagus machipongonensis as the bacterium responsible, which releases a fat-like molecule called RIF-1 that triggers colony formation. While King remains cautious about extrapolating to animal origins, bacteria may have influenced the development of the first animals.
In Pearl Harbor, Michael Hadfield discovered that tube-building worms transform from free-swimming larvae to sedentary adults only when they encounter specific bacterial biofilms. This bacterial dependence isn't unique-sponges, mussels, barnacles, sea squirts, and corals all require bacterial cues to complete their metamorphosis. These biofilms provide crucial information to larvae: they signal a solid, stable surface with sufficient nutrients that isn't toxic.
Most dramatically, microbes shape our immune system. Germ-free animals have severely underdeveloped immunity, demonstrating that an animal's genome alone cannot create a mature immune system. Microbes help create immune cells, develop immune organs, and calibrate inflammatory responses. Without them, animals become vulnerable to both infections and autoimmune diseases-a paradox that challenges traditional views of the immune system as simply defending against microbes.
Rather than viewing the immune system as a military force that distinguishes self from non-self, it's more accurate to see it as ecosystem managers-rangers in a national park who carefully control resident species while expelling problematic invaders. But remarkably, the "creatures of the park" (our microbes) hired the rangers in the first place, teaching them which species to care for and which to evict.
Microbes even influence our brains-the organs that make us who we are. Neuroscientist Paul Patterson discovered that injecting pregnant mice with substances mimicking viral infections produced offspring with autism-like behaviors. When fed the bacterium B. fragilis, the mice's symptoms largely reversed. The researchers theorized that maternal immune responses created leaky guts in offspring, allowing bacterial toxins to reach the brain and trigger behavioral changes.
In humans, the gut-brain axis-a two-way communication system between these vital organs-is well recognized. Stress can change a mouse's gut microbiome, while microbes can affect behavior and stress responses. Though human studies remain limited, early clinical trials show promise, suggesting our gut bacteria may subtly influence our behavior and mental health in ways we're only beginning to understand.
Capítulo 5
The Delicate Balance: Symbiosis, Conflict, and Control
Wolbachia is a remarkable microbe that manipulates its hosts' reproduction to ensure its own survival. Since it can only pass to the next generation through eggs, not sperm, it has evolved multiple strategies to eliminate or manipulate males. It kills male embryos in some species, transforms males into females in woodlice, and enables females to reproduce asexually in certain wasps. Its most successful strategy is cytoplasmic incompatibility, where infected males can only successfully mate with females carrying the same Wolbachia strain.
Despite its parasitic nature, Wolbachia also has beneficial roles. It provides essential functions for certain nematode worms, protects some insects from viruses, enables egg production in specific wasps, and supplies B-vitamins to bed bugs. This dual nature as both parasite and partner makes Wolbachia emblematic of the complex relationships between microbes and their hosts.
There is no such thing as a "good microbe" or a "bad microbe." These simplistic labels fail to capture the complex, contextual relationships in nature. Bacteria exist along a continuum between parasitism and mutualism, with many occupying multiple positions simultaneously. The stomach bacterium Helicobacter pylori both causes ulcers and protects against esophageal cancer. Microbes can shift roles depending on their location-beneficial in the gut but deadly in the bloodstream.
Every symbiotic relationship involves inherent conflict. Partners have their own evolutionary interests that often clash with their hosts'. Cheating is always a possibility, as seen in relationships like oxpeckers that both clean and wound their hosts, or acacia trees that chemically manipulate their ant protectors. As evolutionary biologist Toby Kiers notes, "Symbiosis IS conflict-conflict that can never be totally resolved."
Animals manage their microbial partnerships through physical containment strategies. Insects use specialized cells called bacteriocytes to house their symbionts-sometimes tens of thousands packed tightly together. These cells serve as both homes and prisons, allowing insects to control their microbial partners. Vertebrates like humans face greater challenges, lacking bacteriocytes and needing to manage trillions of microbes that live around our cells rather than within them.
Mother's milk plays a crucial role in shaping infant microbiomes. Human milk contains over 200 different oligosaccharides (complex sugars) that babies cannot digest. These human milk oligosaccharides (HMOs) aren't meant for babies at all-they're food for beneficial microbes, particularly Bifidobacterium longum infantis. As it digests HMOs, B. infantis releases short-chain fatty acids that feed the baby's gut cells and encourages the production of anti-inflammatory molecules that calibrate the immune system.
Our relationship with our microbes continues even during illness. When animals get sick and lose their appetite, they release emergency rations of the sugar fucose to feed their gut microbes until normal eating resumes. The diverse glycans we produce support a wide range of bacteria with different feeding specialties, creating complex food webs where microbes break down molecules for each other and form metabolic truces to avoid competition.
In some cases, hosts and microbes become so interdependent they essentially function as a single entity. This happens when bacteria live inside host cells and are transmitted directly from parent to offspring. Such arrangements trap microbes in an evolutionary spiral of simplification. Isolated from other bacteria and restricted to small populations, these symbionts accumulate mutations that eliminate non-essential genes. Their genomes shrink dramatically-while E. coli has about 4,600,000 DNA letters, the smallest known symbiont Nasuia has just 112,000.
Capítulo 6
When Microbial Partnerships Falter: Disease and Dysbiosis
In the remote Line Islands of the Pacific Ocean, Forest Rohwer discovered a stark contrast between pristine and human-impacted coral reefs. At uninhabited Kingman Reef, he found a Hollywood-perfect ecosystem teeming with sharks and vibrant corals. But at Christmas Island, home to 5,500 residents, he encountered "some of the deadest reefs he'd ever seen"-ghostly, slime-covered coral skeletons in turbid water with few fish and no sharks.
Rohwer discovered that healthy corals maintain a diverse microbiome that creates "colonization resistance" against pathogens through competition for space and resources. As human activity increases, this balance shifts dramatically. From uninhabited Kingman to populated Christmas Island, shark populations collapsed, coral cover dropped from 45% to 15%, and microbial counts increased tenfold.
This transformation revolves around a turf war between corals and fleshy algae. Normally, fish keep algae trimmed, but when humans kill predators and grazers, algae flourish. These algae release dissolved organic carbon (DOC)-essentially sugars-that fuel explosive microbial growth, particularly pathogens. This creates a devastating cycle: dying corals create space for more algae, which release more DOC, feeding more pathogens that kill more corals.
Rohwer's findings represent a Grand Unified Theory of Coral Death, connecting the largest sharks to the smallest viruses and showing how invisible microbes ultimately determine reef fate. This challenges our traditional understanding of disease, which typically involves a single pathogenic microbe causing predictable symptoms. Instead, Rohwer suggests a different type of microbial disease-dysbiosis-where entire communities shift into harmful configurations.
Jeff Gordon, arguably the most influential human microbiome scientist, pioneered the use of germ-free mice to understand how microbes affect health. His groundbreaking experiments showed that obesity could be transferred between animals simply by transplanting gut microbes, with obese-derived microbes causing recipients to gain 47% more fat than those receiving lean-derived microbes.
Gordon's research in Malawi revealed that gut microbes might explain why children with identical backgrounds develop different forms of malnutrition. Children with kwashiorkor have stagnant, immature gut microbiomes that interfere with energy harvesting. Standard therapeutic foods only temporarily affect these dysbiotic communities, which quickly revert to their impoverished state when children return to normal diets-demonstrating the resilience of established microbial ecosystems to change.
The immune system functions like an "immunostat" that stabilizes our relationships with microbes, balancing between repelling pathogens and tolerating beneficial bacteria. Over the last half-century, sanitation, antibiotics, and modern diets have gradually pushed our immunostats to higher settings, resulting in immune systems that overreact to harmless substances.
Inflammatory bowel disease (IBD) exemplifies an overreactive immunostat. Characterized by severe gut inflammation, chronic pain, diarrhea, and fatigue, IBD has soared in developed countries since World War II. The gut microbiomes of IBD patients show less diversity and stability than healthy individuals, lacking anti-inflammatory species like Faecalibacterium prausnitzii while harboring inflammatory ones like Fusobacterium nucleatum.
Our most important microbial friends come from our mothers. C-section births-now accounting for a quarter of UK and a third of US deliveries-deprive babies of vaginal microbes, instead colonizing them with skin and hospital bacteria. This altered microbial trajectory may explain why C-section babies have higher rates of allergies, asthma, celiac disease, and obesity.
Dietary fiber profoundly affects our microbiome and immune function. When bacteria break down fiber, they produce short-chain fatty acids that trigger anti-inflammatory responses. Without fiber, bacteria devour the protective mucus layer covering the gut, bringing them closer to immune cells and potentially triggering inflammation. Through processed foods and limited plant consumption, we are "starving our microbial self."
Antibiotics represent perhaps the greatest disruptors of our microbiomes. These drugs have saved countless lives but also indiscriminately kill beneficial bacteria alongside pathogens-"like nuking a city to deal with a rat." Each treatment temporarily decimates microbial diversity, and while communities largely recover, they never fully return to their original state.
Martin Blaser worries that important microbial species may be disappearing entirely from human populations. Helicobacter pylori, once found in most humans for at least 58,000 years, now appears in just 6% of Western children. Similarly, Bifidobacterium infantis, crucial for infant gut development, appears in 60-90% of babies from developing countries but only 30-40% in developed nations. These disappearances highlight why studying diverse populations matters: most microbiome research has focused on WEIRD countries (Western, Educated, Industrialized, Rich, Democratic), representing just one-eighth of humanity.
Capítulo 7
Evolutionary Dance: How Microbes and Hosts Shape Each Other
When engineer Thomas Fritz impaled his hand on a tree branch, the resulting infection contained bacteria nearly identical to Sodalis, a microbe previously found only inside insects. This discovery revealed Sodalis praecaptivus ("before captivity")-a "missing link" showing what symbiotic bacteria look like before becoming dependent on their hosts. Over time, such microbes can evolve to provide benefits to insect hosts, eventually moving into their cells and losing genes they no longer need, becoming permanent symbionts.
Microbes enter animal bodies through numerous routes beyond impalement. Aphids exchange beneficial bacteria during mating that help them resist parasites and withstand higher temperatures. Woodlice acquire microbes by cannibalizing peers. Mice ingest bacteria from neighbors' droppings. Insects share microbes through "backwash" while feeding on the same plant. These are the same routes-contaminated food and water, unprotected sex, dirty needles-that we associate with disease transmission, but beneficial symbionts travel these paths too.
Once a microbe reaches a new host, it must establish itself despite challenges from the immune system and rival microbes. Some microbes are "preadapted" to symbiosis-like those that naturally break down plant fibers, incidentally releasing nutrients the host can use. These "by-product mutualisms" benefit both partners without either needing to invest in the relationship.
Beewolves-predatory wasps that paralyze honeybees as food for their young-demonstrate remarkable symbiont transmission. Martin Kaltenpoth discovered these wasps secrete white paste containing Streptomyces bacteria from their antennae onto their underground burrows. These bacteria, excellent producers of antibiotics, protect developing beewolf larvae from fungal infections during their nine-month development in humid chambers.
The transmission of microbes from parent to offspring "braids together the fates of hosts and symbionts," ensuring their partnership continues through generations. This creates evolutionary pressure for closer integration-microbes develop abilities that help their hosts, expanding their pool of partners, while animals evolve more efficient transmission methods.
Many insects ensure offspring receive proper microbes through creative provisioning methods. Stinkbugs excel at this-some package microbes in weatherproof capsules laid beside eggs, others embed them in egg-surrounding jelly, while one Japanese species guards her clutch and secretes bacteria-laden mucus for hatchlings to consume.
Humans acquire our first microbes differently-traditionally believed to encounter them during birth when passing through the vaginal canal. While recent studies have challenged the "sterile womb hypothesis" by reporting microbial DNA in amniotic fluid and placenta, these findings remain controversial.
Despite the diversity of transmission routes, all serve the same purpose: moving microbes between host generations. Each animal species actively sculpts its microbiome, allowing only certain bacteria to colonize while excluding others. This selectivity creates distinctive communities that can distinguish humans from chimps or even whales from dolphins sharing the same oceans.
Microbes have preferred partners, with many adapting to colonize specific hosts. When John Rawls exchanged microbiomes between sterile mice and zebrafish, the animals reshaped their new communities to more closely match their native ones-mice "mousified" fish microbiomes and vice versa. An animal's genes act like theater set designers, creating the stage upon which specific microbes perform.
Lynn Margulis coined the term "holobiont" in 1991 to describe the unified collection of organisms that live together. Eugene Rosenberg and Ilana Zilber-Rosenberg expanded this concept to the "hologenome"-the combined genes of host and microbes functioning as the unit of natural selection. While some scientists embrace this holistic view of evolution, others criticize it as conceptually fuzzy, noting that not all host-microbe relationships are equally stable or important.
Microbes might even drive the origin of new species. Seth Bordenstein demonstrated that in certain wasp species, different strains of Wolbachia bacteria prevent successful interbreeding, maintaining species separation. In another case, hybrid wasps developed incompatible gut microbiomes that proved fatal. These examples suggest microbes can create reproductive barriers between populations-potentially driving speciation.
Capítulo 8
Microbial Superpowers: How Symbionts Enable Ecological Innovation
Microbes can transform animals into evolutionary winners by granting them extraordinary abilities to exploit otherwise inaccessible resources and environments. Hemipterans-true bugs with stabbing, sucking mouthparts-are the only animals that exclusively drink plant sap, a lifestyle made possible entirely through symbiotic bacteria. Without these microbes, all 82,000+ species would perish.
Nancy Moran discovered that aphids rely on a bacterium she named Buchnera, which has been their companion for 200-250 million years. Aphids feed exclusively on phloem sap-a sugar-rich but amino acid-deficient diet. Buchnera synthesizes the ten essential amino acids that aphids, like all animals, cannot produce themselves. Neither partner can produce all necessary enzymes alone; instead, their biochemical pathways intertwine between host and symbiont "factories."
Roughly 10-20% of insects depend on nutritional symbionts that provide vitamins, amino acids, or sterols, allowing them to thrive on otherwise inadequate diets. Carpenter ants use Blochmannia bacteria to subsist on largely vegetarian diets while dominating tropical forest canopies. Blood-feeders like lice, bed bugs, ticks and leeches rely on bacteria for B-vitamins missing in blood.
The most extreme examples of symbiotic success exist in the deep ocean. Giant tube worms (Riftia pachyptila) have no mouth, gut, or anus-yet they thrive. Colleen Cavanaugh discovered these worms contained bacteria in their trophosome organ that use sulphur for energy through chemosynthesis. Unlike photosynthesis which harnesses sunlight, these bacteria oxidize sulphides from hydrothermal vents to fix carbon, producing pure sulphur crystals as waste.
Ruth Ley discovered that mammals cluster into distinct microbiome groups based primarily on diet-herbivores had the highest bacterial diversity, carnivores the lowest, with omnivores in between. This pattern exists because plant tissues contain complex carbohydrates that vertebrates can't digest without microbial help. While humans derive about 10% of their energy from microbial digestion, cows and sheep get a remarkable 70%.
Katherine Amato tracked Mexican howler monkeys for thirty weeks, collecting dung to study how their gut microbiomes adapt to seasonal diet changes. When fruit becomes scarce and monkeys switch to leaves, their microbes produce more short-chain fatty acids, providing energy despite lower caloric intake. This microbial adaptability creates nutritional stability despite seasonal food variations.
Plants defend themselves with toxic chemicals, but many herbivores overcome these defenses through their microbiomes. The desert woodrat consumes creosote bush leaves containing resin that would kill other rodents. Kevin Kohl discovered that woodrats from the Mojave Desert (where creosote grows) harbor detoxifying gut bacteria absent in Great Basin woodrats (where creosote doesn't grow). When Kohl eliminated these microbes with antibiotics, experienced woodrats lost their poison resistance.
Sometimes microbial partnerships devastate plant populations, as with the mountain pine beetle infestation killing vast swaths of North American pine forests. These rice-sized beetles carve galleries beneath tree bark, laying eggs as they go. Their fungal partners grow deeper into the trees, extracting nutrients from otherwise inaccessible tissues and delivering them to beetle larvae. The beetles also partner with bacteria like Pseudomonas and Rahnella, which possess genes for degrading terpenes-the trees' chemical defenses.
Capítulo 9
Harnessing Microbes: From Disease Treatment to Environmental Design
When animals partner with microbes, they can accelerate their evolutionary pace from the slow adagio of traditional natural selection to the brisk allegro of microbial adaptation. Unlike animals, bacteria can exchange DNA horizontally between individuals-not just vertically from parent to offspring. This horizontal gene transfer allows bacteria to evolve at blistering speeds, instantly acquiring adaptations from their neighbors rather than waiting for mutations to accumulate.
The Japanese people's long history of eating nori seaweed has equipped their gut microbiomes with special genes for digesting marine carbohydrates. These genes didn't evolve in humans or even in gut bacteria-they came from marine microbes that naturally digest seaweed. When ancient Japanese consumed raw nori, these marine bacteria temporarily entered their guts and shared their seaweed-digesting genes with resident gut bacteria.
Horizontal gene transfer is astonishingly common in the human microbiome. Eric Alm's team found over 10,000 swapped gene sequences between bacteria, with microbes in the human body 25 times more likely to exchange genes than those in other environments. Our bodies function like bustling genetic marketplaces, concentrating microbes together and facilitating DNA exchange between them.
Rather than viewing microbes as enemies to be eradicated, modern microbiologists are adopting a gardening metaphor-selectively cultivating beneficial species while removing harmful ones. A groundbreaking field experiment at California's Dusy Basin demonstrated remarkable success using the purple microbe Janthinobacterium lividum (J-liv) to protect frogs from the deadly Bd fungus. Frogs treated with J-liv showed a 39% survival rate after a year, while untreated frogs all died.
The term "probiotic" means "for life"-the opposite of antibiotics in both etymology and purpose. Yet most commercial probiotics face a fundamental problem: they contain relatively few bacteria compared to the gut's existing population, and these microbes rarely colonize effectively. Despite extensive marketing claims, Cochrane Collaboration reviews find probiotics definitively help with only a few conditions: shortening infectious diarrhea, reducing antibiotic-associated diarrhea, and preventing necrotizing enterocolitis in premature infants.
More promising candidates include naturally abundant gut residents like Akkermansia muciniphila (associated with lower obesity risk), Bacteroides fragilis (which regulates inflammation), and Faecalibacterium prausnitzii (whose absence correlates with IBD). These "stars of the gut" are better adapted to colonize our bodies than current commercial strains.
The most successful method for manipulating the microbiome is fecal microbiota transplant (FMT)-transferring stool from a donor to a patient. Alexander Khoruts demonstrated this with a 61-year-old woman suffering from relentless C. difficile infection. After eight months of failed antibiotic treatments, a single FMT using her husband's processed stool cured her within days. FMT works like an ecosystem transplant, completely replacing a dysbiotic community rather than adding individual strains.
Beyond selecting natural microbes, scientists are engineering bacteria with new capabilities. Pamela Silver created E. coli that can detect tetracycline in mouse guts, turning blue to report drug exposure. These bacterial "journalists" could monitor the largely inaccessible gut environment, sensing toxins, pathogens, or disease markers. Matthew Wook Chang has engineered bacteria to hunt Pseudomonas aeruginosa, releasing enzymes to break apart bacterial communities and antibiotics to kill the fragments.
In January 2011, Scott O'Neill released mosquitoes from a plastic cup in Cairns, Australia-the culmination of decades of work to combat dengue fever. His approach? Release more of the very Aedes aegypti mosquitoes that transmit the disease, but with a crucial difference: they carried Wolbachia, a bacterium that prevents dengue viruses from replicating in the insects. After extensive community engagement, O'Neill's team released 300,000 Wolbachia-carrying mosquitoes. Within four months, 80-90% of local mosquitoes carried the protective bacteria.
Jack Gilbert's home in suburban America serves as a living laboratory for understanding how humans interact with microbes. The Gilbert family's Home Microbiome Project revealed that houses quickly take on the distinctive microbial character of their inhabitants, with light switches, doorknobs and surfaces colonized within 24 hours of moving in.
Rather than excluding microbes from buildings, Jessica Green advocates for "bioinformed design"-deliberately shaping our buildings to select for beneficial microbes. Just as farmers plant wildflower strips to attract pollinators, architects could implement design features that boost microbial diversity. Every architectural choice affects building microbial ecology, which in turn shapes our own microbiomes.
With microbes in mind, our world transforms. People become "mobile ecosystems," cities reveal their "microbial underbellies," and everyday actions like handshakes become exchanges of living organisms. This perspective-seeing microbes as partners to be cherished rather than enemies to destroy-drives scientific exploration and may ultimately transform human health and our relationship with the natural world.
