The first time, I looked forward to the night feeds. The room was dark, and the only sounds were her small, quick swallows and, now and then, a sigh. She was warm and heavy against me, heavier than the week before, and her head smelled sweet, like milk. That is the half I want to keep. In the other half, my hormones swung by the hour, I was hungrier than I had ever been, and I did not sleep. She wanted to be up at night like a little monster, and spent her days as a peaceful baby.

Painters have shown mothers nursing for centuries. In Europe, many of them painted the Virgin Mary with the baby at her breast. In the Madonna Litta, painted around 1490 and credited to Leonardo da Vinci or his workshop, a mother looks down at the baby she is feeding (Figure 1). Her red dress has a slit sewn over each breast, for nursing. Her face is calm. The baby holds still and looks out at whoever is looking in. The painters kept to the calm, and to one direction: milk goes from the mother into the baby.

Figure 1. Madonna Litta, about 1490, attributed to Leonardo da Vinci. State Hermitage Museum, Saint Petersburg. Public domain, via Wikimedia Commons.

At 2 a.m., in another house, a six-week-old with a cold stops feeding to breathe. A reel on her mother’s phone says the baby’s spit is talking back to the milk. The baby’s nose is blocked, so she lets go with a small wet snort, then latches again. Her forehead is warm against her mother’s arm. The post says the breast learns what the baby has caught. The milk, it says, answers with antibodies made for that germ.

Her mother sends the post to the twelve mothers from her prenatal class before the feed is over, her thumb sticky with milk. Part of the claim was measured. Part of it was a guess.

In 2012, a team in Haifa, Israel, led by the newborn doctor Arieh Riskin, sampled the milk of mothers whose babies were in hospital with a fever. The babies were all three months old or younger. Each mother gave milk while her baby was sick, and again after the baby got better. Across the mothers of 31 sick babies, the milk held a median of about 5,700 white blood cells per milliliter during the illness. After recovery, it held about 2,100. White blood cells are the body’s germ fighters. In the milk of mothers of 20 healthy babies, the counts did not move that way.

The antibodies did not follow. The main antibody in milk did not change much between the sick days and the well ones. Riskin’s team picked mothers by the baby’s illness. The study also did not show how the breast would know the baby was sick.

A mother’s own infection is a separate case, and I have had one. Two months after my first daughter was born, the thermometer read 39.1 °C, and I was sure breastfeeding was over. My obstetrician said to keep going. When a mother catches an infection, her body makes antibodies against the germ, and some pass into her milk, antibodies a baby can borrow. Stopping would take those antibodies away.

In 2013, a team in Perth, Australia, led by Foteini Hassiotou, followed 21 mothers. In healthy pairs, white blood cells made up 0 to 2 percent of the cells in milk. When the mother or the baby caught an infection, the share rose, as high as 94 percent. It fell back after recovery. In three of the infections they recorded, the baby alone was sick.

Hassiotou’s team also offered a route. During a feed, milk comes in waves. At the end of each wave, the milk ducts shrink, and some milk flows back into the breast, “likely together with saliva from the baby’s mouth.” The team did not measure that backflow.

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Figure 2. What milk carries and what science has yet to learn about it, from the evolutionary biologist Katie Hinde at TEDWomen 2016. Video and thumbnail: TED, CC BY-NC-ND 4.0.

Say you are one of the twelve. You wake at six to a baby who coughed all night, and the reel is the first thing on your screen. Twelve babies’ next fevers now depend on one post, and none of their mothers can tell which half was measured. The two-month checkup is a few weeks off. Whichever half you trust by then is the half you act on at the next fever.

Two earlier pieces read a 2024 review of the microbiome by Ziqi Ma and colleagues: what the microbes are, and what they do. This last one asks how a baby’s first microbes get in, and whether anything comes back out. Systems thinking calls a chain of effects that comes back to change where it started a loop. The reel claims a whole one: a baby’s cold reaches the breast, and the milk answers the cold.

A guess like Hassiotou’s can be checked piece by piece. If spit flows back into the breast, bacteria from the baby’s mouth should turn up in the milk. In 2025, Pamela Ferretti, Ran Blekhman and colleagues published a study of 195 mothers and babies in Minneapolis. They went looking for something else: which bacteria live in milk, and which of them settle in a baby’s gut. Mouth bacteria turned up in the milk anyway. Which way they had traveled was a harder question.

What a Pump Can Catch

In Minneapolis, a mother feeds her baby until the baby is full. Two hours later, she switches on a hospital pump, the heavy electric kind. It hums while she empties her right breast until the milk stops. The tubing and the bottle are sterilized. Within twenty minutes, the milk is in a freezer at minus 80 degrees Celsius.

In all, 195 mothers and babies went through some version of this. Mothers gave milk at one month and three months after birth. Babies gave stool, from a diaper, at one month and six months. Ferretti’s team, at the University of Chicago and the University of Minnesota, read those 507 samples.

Milk is hard to search for bacteria. The bacteria counted in milk in part one are real, but next to stool they are few: most of the milk is fat and the mother’s own cells. A pea-sized scoop of stool is crowded with bacteria.

Most earlier milk studies used a method called 16S sequencing. It copies one gene that every bacterium carries, then reads that one gene. The copying starts from a primer, a short piece of DNA that has to fit the gene. A primer works like a key cut for one lock, the same trouble as a DNA kit that looks for only one key. Bacteria whose gene fits get copied more. A real lock stays shut to the wrong key. A poor fit here still makes some copies, only fewer. Those studies mostly found Staphylococcus and Streptococcus, bacteria common on skin and in the mouth.

Ferretti’s team used shotgun sequencing. It breaks all the DNA in a sample into pieces and reads every piece, with no primer aimed at one gene. In their milk, the most common bacterium was Bifidobacterium longum, a gut bacterium of breastfed babies. It turned up in 55 percent of the milk samples and 98 percent of the babies’ stool.

For the gap between the two methods, the team points first to the primer. The common primers were not built to fit Bifidobacterium, so the older method may have missed much of it. A parent who reads that milk is mostly Staphylococcus may be reading the older method. In the next article about milk, the word to look for is “16S” or “shotgun.”

One kind of B. longum is B. infantis, a bacterium that can live on the milk sugars a baby cannot digest. Those sugars are food sent ahead for bacteria. In this study, the milk carried the bacteria too. Food and seed arrived together. Whether the seed takes is a question for the gut.

Who Stays

A gardener tips a rattling packet of mixed seed into one bed. In the packet, a dozen kinds fit side by side. In the soil, they compete for light and water, and one kind can take over.

A baby’s gut works like that bed. In the milk, three kinds of Bifidobacterium often lived side by side, in similar amounts: B. longum, B. breve and B. bifidum. In the babies’ guts, they mostly did not. One of them, or something else entirely, usually took over. The team reads this as “a higher level of competition” in the gut than in the milk. Unlike a garden bed, a baby’s gut is planted by whatever arrives.

The team sorted each stool sample by its most common bacterium. At one month, 68.5 percent were led by bacteria outside Bifidobacterium, mostly two common gut groups, Escherichia coli and Bacteroides. By six months, that share had fallen to 28.1 percent. The share led by B. longum rose from 15.7 to 46.6 percent. In the stool samples that had B. infantis, its average share rose from about 3 percent of the gut bacteria to about 24 percent. Babies whose gut was led by B. longum at both visits had the steadiest gut of all.

Between one and six months, B. longum and B. breve grew in babies fed breast milk alone, and Clostridium perfringens, a cause of food poisoning, shrank. In babies who also had formula, B. longum grew too. That line is for the parent who gives a bottle of formula at night and wonders what it costs the gut.

Across all 195 pairs, the amount of Bifidobacterium in a mother’s milk did not predict the amount in her baby’s gut, though in some pairs it did. Henri Tissier, in 1899, gave the milk the credit for what grew in breastfed babies. Here, how much seed the milk carried did not settle it.

The team names what else might decide: the bacteria already in the gut, the baby’s own genes, what there is to eat, and how much oxygen reaches the gut wall. Two of them, food and oxygen, are limits a body sets on its microbes, the managing part one described. The study did not test them, and which matters most is still unknown.

That is the Ackoff test of a system again: a part’s effect depends on the other parts. One seed lands differently in a different bed. And one species name in milk and in stool does not make it the same bacterium.

Which Way the Strains Went

A family walks into a shelter looking for the beagle they lost last week. A dog barks from every pen. The family walks past the shepherds and the terriers to the one beagle, then checks for the torn left ear.

Telling bacteria apart works like that. The species is the dog. A strain is the breed, and each one carries its own small changes in its DNA, its torn ear. Finding B. longum in a mother’s milk and in her baby’s stool is finding a dog in every pen: almost every baby had it. Finding the same strain in both, down to its small changes, says much more. One limit: a strain is millions of nearly identical cells, where a dog is one animal.

The team rebuilt the DNA of 77 strains. Sixty-five came from the babies’ stool. Twelve came from milk at one month, since the milk held too little bacterial DNA to rebuild more. The team found twelve cases where one strain turned up in a mother’s milk and in her own baby’s stool. The matches came from six mother-baby pairs and covered ten kinds of bacteria. Every strain they could rebuild from milk turned up in that mother’s baby. So twelve is a floor, and more milk DNA would likely find more.

Figure 3. Six of the twelve matches, in four species. In each tree, an orange dot (a mother’s milk) lands on the same branch as purple dots (her own baby’s stool). Gray boxes mark strains that stayed in one baby from one month to six. From Ferretti et al. (2025), Fig. 3D, CC BY 4.0; cropped, nearby panels removed.

One match was Klebsiella pneumoniae, a gut bacterium that is often harmless. In newborns, it has been linked to sepsis, a dangerous infection of the blood. It is the kind of microbe part two called harmful only under the right conditions. None of the babies in the study showed signs of illness, and no mother reported a breast infection.

Two other matches were Streptococcus salivarius and Rothia mucilaginosa. Both usually live in the mouth. They are what a baby’s spit would leave in the milk if Hassiotou’s backflow is real. So the arrow may run both ways. Milk may seed the baby’s gut, and the baby’s mouth may seed the milk. If so, milk is half of a loop.

Which way came first is still unknown. The first milk samples came at one month, too late to see. A mother and a baby also share a home and the people in it, and housemates share strains too. Both could have picked up a strain somewhere else.

Strains also come and go between the one-month and six-month visits. Of the strains in a baby’s stool at the first visit, 19 percent were still there at the second. Of the strains shared with the milk, 25 percent were. Babies born vaginally kept more of their strains than babies born by C-section. Antibiotics, and whether the baby still had breast milk alone at six months, made no clear difference.

For the mother who forwarded the reel, the study checks part of the guess: bacteria from a baby’s mouth may reach the milk. What this study found was bacteria, not a message about the cold. Ask the reel what carried the message, and whether anyone watched it travel. A strain that travels can also carry more than itself.

Who Shares More

At one month, the babies’ stool carried more genes for resisting tetracycline than for any other antibiotic. So did the milk. Doctors avoid tetracycline in pregnancy and in children under eight, because it can stain growing teeth permanently.

These resistance genes let a bacterium survive an antibiotic, and they can pass from one bacterium to another. Two thirds of the babies had taken no antibiotics by six months. Many babies with no antibiotics on record, before, during or after birth, still carried the genes. Babies whose gut was led by Bifidobacterium carried fewer.

Across all the pairs, a mother’s milk and her baby’s stool showed no link in resistance genes. But a pattern across a whole group can hide what happens inside each pair. So the team asked a narrower question: does a baby share more resistance genes with its own mother than with a stranger?

Their test works like a daycare at pickup time with every baby handed to a random mother. Count the genes each baby shares with the mother holding it. Shuffle again, and count again, 1,000 times. That gives the amount of sharing that chance alone produces. Then compare the real pairs. Statisticians call this a permutation test. Unlike a real daycare, the team shuffled the milk samples’ labels on a computer, and no baby left its mother.

The real pairs shared more than the shuffled ones. The shuffle runs on an old logic: write down everything chance could produce, then see how rare the real result is. Here, a result as large as the real one turned up in fewer than 16 of the 1,000 shuffles.

Figure 4. The shuffle, done by hand. The statistician John Rauser asks whether mosquitoes prefer beer drinkers, shuffles the beer and water labels again and again, and finds the real difference out past almost every shuffle. Video: O’Reilly, Strata + Hadoop World 2014, Standard YouTube License.

Two pairs stood out, pairs 1 and 173. They shared the most resistance genes, and they were two of the six pairs with matching strains. Their samples also gave the most bacterial DNA to read, first and third in the study, and more DNA means more chances to find a match.

The shuffle question works on more than genes. When spit and milk share a strain, or two people in one home share a cough or a claim, the question is whether a stranger would share it too. The mother in the group chat who forwarded the reel is the one to send this to, with that question attached. She can ask it before her next forward, or at the two-month checkup. At six o’clock the shuffle ends, and each baby goes home in the arms that fed it.

A Closing Invitation. The reel stood for a message sent back from baby to mother. The message was a guess; the bacteria were real. Milk carries bacteria to a baby, a baby’s mouth may carry them back, and the gut decides who stays.

1. Find the second path. The next time a baby feeds near you, or a toddler hands you a wet, half-eaten cracker, watch the trade both ways. Milk goes in and spit comes back; a spoon goes from one mouth to the other. What just moved, and which way? Which cold last went around your house that way?
2. Split the reel. Before your next forward, or with the last one you sent, read the post aloud and say which half was measured and which a guess. The milk reel: white cells measured, the route guessed. A teething remedy or a sleep tip splits the same way. Which half would you still send?
3. Bring one claim to the exam room. The baby’s two-month visit counts, and so does your own. With the paper on the exam table crinkling, ask the doctor about one claim from the group chat: was it measured, and in whom? Would a stranger show it too?

At the next 2 a.m. feed, a baby lets go of the breast to breathe, and a little of her spit may slip back with the milk. The milk does not read it. It carries it home.

Where This Came From

Ferretti’s study is one of the first to match strains between milk and a baby’s gut. The team found only one earlier metagenomic study that did. Matching strains between a mother’s gut and her baby’s gut is older and better studied, and it finds far more sharing than milk does.

Intellectual Honesty Note. The births, the night feeds and the fever night, with its 39.1 °C reading, are my own, and the reading of the Madonna Litta is this piece’s. The mother at 2 a.m., the reel, its group chat and the twelve mothers are a composite; the reel paraphrases a common claim, not one post. Riskin’s abstract does not report the mothers’ own health. The mother at the pump is drawn from the study’s methods. The key and lock, the seed bed, the beagle and the daycare are illustrations. This piece describes what milk carries, not how anyone should feed a baby. The study is observational: it cannot show that milk caused any gut change. Only 25 milk samples were sequenced at three months. The primer explanation is the team’s proposal, not a test. The 16 in 1,000 reads the paper’s bound (p < 0.016, from 1,000 shuffles) as a count.

References

Centers for Disease Control and Prevention. (2025). Influenza (flu) and breastfeeding. https://www.cdc.gov/breastfeeding-special-circumstances/hcp/illnesses-conditions/flu.html

Ferretti, P., Allert, M., Johnson, K. E., Rossi, M., Heisel, T., Gonia, S., Knights, D., Fields, D. A., Albert, F. W., Demerath, E. W., Gale, C. A., & Blekhman, R. (2025). Assembly of the infant gut microbiome and resistome are linked to bacterial strains in mother’s milk. Nature Communications, 16, 11536. https://doi.org/10.1038/s41467-025-66497-y

Hassiotou, F., Hepworth, A. R., Metzger, P., Tat Lai, C., Trengove, N., Hartmann, P. E., & Filgueira, L. (2013). Maternal and infant infections stimulate a rapid leukocyte response in breastmilk. Clinical & Translational Immunology, 2(4), e3. https://doi.org/10.1038/cti.2013.1

Hinde, K. (2017, March 28). What we don’t know about mother’s milk [Video]. TED. YouTube. https://www.youtube.com/watch?v=Bo8YN3oB0Cw

Leonardo da Vinci (attributed). (ca. 1490). Madonna Litta [Painting]. State Hermitage Museum, Saint Petersburg. Public domain image via Wikimedia Commons.

Ma, Z., Zuo, T., Frey, N., & Rangrez, A. Y. (2024). A systematic framework for understanding the microbiome in human health and disease: From basic principles to clinical translation. Signal Transduction and Targeted Therapy, 9, 237. https://doi.org/10.1038/s41392-024-01946-6

Rauser, J. (2014, October 17). Statistics without the agonizing pain [Video]. O’Reilly. YouTube. https://www.youtube.com/watch?v=5Dnw46eC-0o

Riskin, A., Almog, M., Peri, R., Halasz, K., Srugo, I., & Kessel, A. (2012). Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant. Pediatric Research, 71(2), 220–225. https://doi.org/10.1038/pr.2011.34

They had fed mice Salmonella, the germ behind food poisoning, to find out. For healthy mice, it took about 100,000 germs to give 5 out of every 10 a gut infection. The mice that took fewer than three had been given one dose of an antibiotic, a drug that kills bacteria, the day before. The drug had killed many of the bacteria living in the mice’s guts, and those bacteria had been keeping the newcomers out. So the answer for the ten-year-old is: it depends on who already lives there.

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Figure 1. The gut’s trillions of microbes and what they do for health, from BBC Global’s Health Decoded (2024), with science journalist Melissa Hogenboom. Video and thumbnail: BBC, Standard YouTube License.

The skin has guards of its own. In 2010, Tadayuki Iwase and colleagues at Jikei University in Tokyo studied Staphylococcus aureus, a bacterium that causes skin and blood infections. They found strains of a common skin bacterium that make a protein breaking up the films S. aureus grows in. Of 88 volunteers, those who carried those strains in their noses rarely carried S. aureus. When the team put such a strain into the noses of volunteers who did, the S. aureus was gone. Bohnhoff took the guards away, and the door opened. Iwase added one, and it shut.

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Figure 2. How the bacteria on skin make it a poor home for invaders, help hold the skin together and train the immune system, from Nature Video (2020). Video and thumbnail: Springer Nature, Standard YouTube License.

Say you stand at the pharmacy counter this month with a prescription for your child’s earache: an antibiotic, twice a day for ten days. The paper bag crinkles as the pharmacist folds it shut. Some ear infections get better without antibiotics, and you have not asked whether this is one. The drug cannot tell the germ it was sent for from the crowd in your child’s gut. One dose thinned that crowd in Bohnhoff’s mice enough to let three germs in. Ten days leave your child’s gut with fewer guards at its door until the crowd grows back.

Bohnhoff’s mice and Iwase’s volunteers show one idea from a 2024 review by Ziqi Ma and colleagues. The microbes defend the body, and they teach the immune system what to fight. The first part of this series followed four of the review’s ideas, on what the microbes are and where they live. The review names three more. The microbes and the body’s cells share one fluid, and each side changes it for the other. When the two sides stop holding each other in check, the body tips toward illness. And the microbes may help set the targets a body holds steady. Each is a loop between the two sides, the kind systems thinking follows.

A body holds some numbers steady, its temperature among them, the way an oven holds the heat it is set to. In a fever, the brain turns its own dial up by one or two degrees Celsius, the body shivers to catch up, and the target moves first.

Ma’s team argues that the microbes keep a second hand on the same dial. If ten days of pills can thin the guards in a child’s gut, how much of the turning were those guards doing?

What Keeps the Door Shut

In 1958, four years after Bohnhoff’s mice, surgeons in Denver ran the experiment in reverse. Ben Eiseman’s team gave four patients with a severe gut infection an enema of a healthy donor’s stool, and the response, they wrote, was “immediate and dramatic.” The idea waited half a century for a proper test.

The infection is now usually traced to Clostridioides difficile, a bacterium that multiplies when antibiotics clear out its rivals. It often comes back after each new course of the drug. In 2013, Els van Nood, Josbert Keller and colleagues in Amsterdam tested a donor’s stool against the standard antibiotic, vancomycin, in 42 patients whose infection kept returning. The stool was mixed with salt water and passed through a thin tube from the nose into the small intestine. Thirteen of the sixteen patients in the donor group were cured by the first infusion. On vancomycin alone, four of thirteen were. The gap was so wide that the trial was stopped early. It was a small trial, but a stranger’s microbes had taken the space back.

Resident microbes keep newcomers out in several ways. They eat the food a newcomer needs. Some make poisons aimed at rivals, like the protein Iwase’s nose strains made against S. aureus. Some change the place itself. In the vagina, Lactobacillus bacteria make lactic acid, which keeps the vagina too acidic for many germs that cause infections.

The microbes also teach. The Amish of Indiana and the Hutterites of South Dakota both came to America from Europe as German-speaking farmers, and their genes are close. They farm differently. Amish families keep dairy cows and work fields with horses, and the barns stand a few steps from the house. Hutterites live on large communal farms run with modern machines. In 2016, Michelle Stein, Carole Ober and colleagues compared the two. About 5 percent of Amish children had asthma, against 21 percent of Hutterite children. The dust in Amish homes held almost seven times as much endotoxin, a molecule from the outer coat of many bacteria.

The team then tested the dust. When they put Amish house dust into the airways of mice, it protected the mice from asthma attacks. Hutterite dust did not. In 60 children, 30 from each group, the Amish children’s immune cells were tuned differently, more toward fighting germs and less toward allergy. Two communities are not a trial. The mouse experiments are what point to the microbes in the dust.

Medicine already counts several ways to gain protection after birth. A body can fight off an infection and remember it. A vaccine can teach it. A baby can take antibodies from milk, and whether anything travels back the other way is the last part of this series. Ma’s team adds the microbes to that list and calls it acquired microbial immunity (Figure 3). It is gained by living among the right microbes, as the Amish children did, or by medicine, as the Amsterdam patients did. Ma’s review counts milk sugars among the ways it is gained, since they feed a baby’s gut bacteria at every meal. It can be lost to one dose of the wrong drug.

Figure 3. Ways to gain protection after birth, with Ma’s addition in the bottom row. Adapted from Ma et al. (2024), Fig. 2, CC BY 4.0; simplified and redrawn, leaving out milk sugars and probiotic products.

That loss has a place in an ordinary year: the pharmacy counter. Anyone handed an antibiotic for a cough, an earache or a sore throat can ask two questions before the first pill. Is this infection caused by bacteria? Antibiotics do nothing against a virus, and most colds are viral. Is there a narrower drug that leaves more of the gut alone? A friend with a toddler and a winter of earaches ahead may want the two questions too. When the first answer is yes, the drug is doing its job. Skipping the questions costs nothing that day. Any cost comes later, in a gut with fewer defenders, like the mice that three germs could infect. Ma’s team claims those microbes also help set the body’s targets, starting with its temperature.

Who Set Normal

In 1868, the German physician Carl Wunderlich published the temperatures of about 25,000 patients. He took them under the arm with a thermometer about a foot long, which needed more than fifteen minutes for each reading. He put normal at 37 °C.

In 2020, Myroslava Protsiv, Julie Parsonnet and colleagues at Stanford checked Wunderlich’s number against the records of about 189,000 people. The records ran from Civil War veterans, through a national health survey in the 1970s, to Stanford patients seen in 2017. Body temperature had fallen about 0.03 °C for every decade of birth. Men born in the early 1800s ran 0.59 °C warmer than men today. Like the fever, the target had moved. This move took two centuries, and the textbooks kept saying 37.

Mice raised without microbes run colder than mice with them. Kale Bongers, Robert Dickson and colleagues at the University of Michigan showed it in 2023, and mice whose gut bacteria were wiped out with antibiotics ran colder too. In 116 patients in hospital, the mix of gut bacteria on arrival predicted how each patient’s temperature would change. A link like that does not prove a cause.

A body holds its temperature with a balancing loop, a loop that pushes back whenever a reading drifts from its target. The fever’s shivering is that loop at work. Once the brain raises its set point, the temperature the body aims for, the body is for a while colder than its own new target. As on a cold night, it pulls blood away from the skin, and the hands go cold. The thermometer climbs while the person under the blanket feels freezing.

The physiologist Walter Cannon gave this steadiness its name, homeostasis. The loop does the holding. An oven answers to one hand. A body holds many targets at once. In Ma’s view, the microbes are a second hand choosing where the loop holds, a role the team calls homeostatic reprogramming.

Every range printed on a lab report assumes a target the loop is steering toward. The range beside each number comes from many other people. At the next checkup, a useful question is not only “Is this in range?” but “Is this where I usually am?” Last year’s report, held next to this year’s, answers it in a minute. A partner’s reports work the same way. Skip the comparison, and a number can drift for years inside the printed range before anyone looks.

My daughters have had no antibiotics so far. When my first daughter ran a fever at about 18 months, she would not touch her solid food and nursed mostly for comfort. The only medicine she got was acetaminophen. I took her temperature. It moved from 39.4 °C to 38.9 °C. The line the pediatrician’s office gave me was 38 °C, 100.4 °F: no higher. That line is the same for every child. It says nothing about where one child’s own normal sits.

If the microbes help choose where the loop holds, could thinner gut communities explain part of the drop since Wunderlich?

Ma’s team offers the idea as a hypothesis. Protsiv’s team pointed to fewer chronic infections. Both explanations run through microbes, and neither team tested the other’s.

The microbial ecologist Allan Konopka warns that biologists tend to expect a “balance of nature,” a steady state every system returns to. Anything else gets read as noise. A normal that drifts over two centuries is easy to miss. So is a normal that two sides hold at once, such as the low oxygen in the thin layer of fluid next to the gut wall.

Where the Oxygen Goes

Right next to the gut wall, there is almost no oxygen, and the body’s own cells keep it that way. The cells that line the colon run mostly on butyrate, the fatty acid from fiber that sealed a leaky brain barrier in part one. Its name comes from butter, and its acid gives rancid butter its sour smell.

Burning butyrate takes oxygen, and the cells take that oxygen from the edge of the gut. That suits the bacteria that make butyrate, because most of them cannot live where there is oxygen. The layer by the wall works like a shared room. The bacteria feed the cells, and the cells keep the room low on oxygen. The room runs on a reinforcing loop: each side keeps the other going.

In 2017, Mariana Byndloss, Andreas Bäumler and colleagues at the University of California, Davis, broke the loop with antibiotics in mice. The drugs killed the butyrate makers. Without butyrate, the colon cells switched to burning sugar, which uses less oxygen, and more oxygen reached the gut. E. coli and Salmonella can breathe that oxygen, and they multiplied. Ma’s team calls this shared life cell-microbe co-ecology. When one side shifts, the room shifts, and the room decides who can live in it.

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Figure 4. Salmonella, one of the germs that move in when oxygen reaches the gut, from The Washington Post (2018). Video and thumbnail: The Washington Post, Standard YouTube License.

The Davis work was done in mice, but an antibiotic course in a person can thin the butyrate makers too. Loose stools in the days after the pills are one sign the room has shifted. A short message to the doctor or pharmacist can ask how long that should last and when to call. In the month after an antibiotic, a person is up to 10 times more likely to catch C. difficile, the germ from the Amsterdam trial. Age over 65 and a stay in a hospital or nursing home raise the risk again, so a grandparent in care has the most to ask about. For them, C. difficile can be life-threatening. The room shifts with every meal, too.

How Health Tips

A meal of eggs carries choline, a nutrient in the yolk. Some gut bacteria turn choline into a gas that smells like fish, and the liver turns that gas into TMAO. In 2016, Weifei Zhu, Stanley Hazen and colleagues at the Cleveland Clinic followed more than 4,000 heart patients. Patients in the top quarter for TMAO had 1.64 times the risk of a heart attack or stroke.

The comparison is with the bottom quarter over three years, after allowing for other risk factors. In the lab, TMAO made platelets, the blood cells that start a clot, quicker to react. The study measured TMAO in the blood and did not track diet, so it does not by itself make a case against eggs. A bowl of oats or beans carries fiber the body cannot digest, and that fiber ends as butyrate for the colon wall. One gut can run both routes at once. Which one wins depends on the meal and on which bacteria are there to meet it.

Ma’s team puts the last idea of the framework into one model of health and illness. The body needs four things from its microbes, and each can fail (Figure 5). It needs enough contact with microbes, kept in check. Too little, at the extreme, is what Ma’s team calls germ-free syndrome: the faults of animals raised with no microbes at all. Too much is overgrowth, such as bacteria spreading up into the small intestine, where they cause bloating and pain. It needs a gut wall that holds, so that bacteria and their parts stay out of the blood. It needs more helpful products than harmful ones, butyrate on one side and TMAO on the other. And it needs steady control as the microbes change, because bacteria mutate.

Figure 5. Four things the body needs from its microbes, and how each one fails. Adapted from Ma et al. (2024), Fig. 7, CC BY 4.0; simplified and redrawn.

In 2022, Yi Yang, Noah Palm and colleagues at Yale put one strain of Enterococcus gallinarum, a gut bacterium, into eight germ-free mice. After three months, it had picked up 159 new mutations and split into two lines. One kept to the open gut. The other adapted to the gut lining, slipped past the immune system, and spread to the lymph nodes and the liver. There it caused more inflammation. Ma’s team rules out any simple list of good and bad bacteria. “In a rigorous sense, all human microbes exhibit conditional pathogenicity,” they write. Any of them can cause harm under the right conditions. What a microbe does depends on what it is connected to.

When all four needs hold, the body stays in charge, and the microbes’ hand on the dial helps it. When they fail, the microbes take over, and the body drifts toward illness. The model leaves open which side pushed first.

In an ordinary week, an antibiotic course thins the contact. A week of white bread and no beans leaves the butyrate makers hungry, and the wall’s cells with them. The question at the next grocery run is which meals feed the bacteria that feed the wall. The snack within reach right now has a fiber line on its label. The same pot feeds everyone at the table. Skip the question, and nothing changes this week. The butyrate makers just stay hungry. A pot of lentils simmering on a weeknight stove feeds the table and the bacteria that feed the wall.

A Closing Invitation. Three germs could infect Bohnhoff’s mice because the door their microbes held had been opened. Their hand is on the body’s dial too: helping set a temperature, and deciding which way a meal runs.

1. Find your own normal. Tomorrow morning, before coffee, start a sticky note inside the medicine cabinet door with your temperature and a partner’s or child’s. The cool tip goes under the tongue, then the beep. Is it 37, or lower, like most people’s now? The next fever gets read against that note.
2. Write down the before. The next time an antibiotic comes home, for you or a child, write one line on the first day: how the stomach feels, which meals sit well. Two weeks after the last dose, does the gut feel the way that line says? If not, which of those meals carry fiber for the gut bacteria that feed the gut wall?
3. Ask what number means call. This month, at a checkup or in a message to the doctor’s office, ask which temperature means call, with the sticky note beside you. If your normal runs below 37, does the line move with it? Then the next shivering night can be what it is: a body chasing a target it moved.

The label on the pharmacy bag names one germ and ten days of pills. It does not name the crowd those pills will thin, or the dial that crowd was helping hold.

Where This Came From

Ma’s homeostatic reprogramming builds on Claude Bernard, who wrote in the 1800s of the milieu intérieur, the inner fluid a body keeps steady around its cells. Ma’s team adds the microbes as a fourth force beside the nervous, immune and metabolic systems, and asks whether “steady” was ever the right word.

Intellectual Honesty Note. The ten-year-old in the opening and the pharmacy counter scene are hypotheticals. My first daughter’s fever and the 38 °C line are my own. The fall in average body temperature is read here as a lower target; Protsiv’s team measured temperatures, not set points. Ma et al. (2024) is a narrative review, and its ideas are proposals, not settled findings. Ma’s review gives cell-microbe co-ecology no section of its own; it gets one here. The hand on the dial and the oven are devices: a body’s set points are held by loops of nerves, hormones and cells, not turned by a hand. Bohnhoff’s team used a Salmonella strain resistant to streptomycin; Ma dates the study 1967, and the 1954 paper is the original. Bongers’ results are reported from the abstract.

References

Bohnhoff, M., Drake, B. L., & Miller, C. P. (1954). Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proceedings of the Society for Experimental Biology and Medicine, 86(1), 132–137.

Bongers, K. S., Chanderraj, R., Woods, R. J., McDonald, R. A., Adame, M. D., Falkowski, N. R., Brown, C. A., Baker, J. M., Winner, K. M., Fergle, D. J., Hinkle, K. J., Standke, A. K., Vendrov, K. C., Young, V. B., Stringer, K. A., Sjoding, M. W., & Dickson, R. P. (2023). The gut microbiome modulates body temperature both in sepsis and health. American Journal of Respiratory and Critical Care Medicine, 207(8), 1030–1041.

Bryce, E. (2018, January 8). How does your immune system work? [Video]. TED-Ed. YouTube. https://www.youtube.com/watch?v=PSRJfaAYkW4

Byndloss, M. X., Olsan, E. E., Rivera-Chávez, F., Tiffany, C. R., Cevallos, S. A., Lokken, K. L., Torres, T. P., Byndloss, A. J., Faber, F., Gao, Y., Litvak, Y., Lopez, C. A., Xu, G., Napoli, E., Giulivi, C., Tsolis, R. M., Revzin, A., Lebrilla, C. B., & Bäumler, A. J. (2017). Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science, 357(6351), 570–575.

Cannon, W. B. (1929). Organization for physiological homeostasis. Physiological Reviews, 9(3), 399–431.

Centers for Disease Control and Prevention. (2025). Healthy habits: Antibiotic do’s and don’ts. https://www.cdc.gov/antibiotic-use/about/index.html

Centers for Disease Control and Prevention. (2026). About C. diff. https://www.cdc.gov/c-diff/about/index.html

Eiseman, B., Silen, W., Bascom, G. S., & Kauvar, A. J. (1958). Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery, 44(5), 854–859.

Hogenboom, M. (2024, October 8). How your gut microbes shape your health [Video]. BBC Global. YouTube. https://www.youtube.com/watch?v=aEhrcIZE1ZM

Iwase, T., Uehara, Y., Shinji, H., Tajima, A., Seo, H., Takada, K., Agata, T., & Mizunoe, Y. (2010). Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature, 465(7296), 346–349. https://doi.org/10.1038/nature09074

Konopka, A. (2026, May 6). Systems thinking [Substack post]. https://thinkmicrobe.substack.com/p/systems-thinking

Ma, Z., Zuo, T., Frey, N., & Rangrez, A. Y. (2024). A systematic framework for understanding the microbiome in human health and disease: From basic principles to clinical translation. Signal Transduction and Targeted Therapy, 9, 237. https://doi.org/10.1038/s41392-024-01946-6

Nature Video. (2020, December 16). The skin microbiome: A healthy bacterial balance [Video]. YouTube. https://www.youtube.com/watch?v=MWE3U3FItlc

Protsiv, M., Ley, C., Lankester, J., Hastie, T., & Parsonnet, J. (2020). Decreasing human body temperature in the United States since the Industrial Revolution. eLife, 9, e49555.

Stein, M. M., Hrusch, C. L., Gozdz, J., Igartua, C., Pivniouk, V., Murray, S. E., Ledford, J. G., Marques dos Santos, M., Anderson, R. L., Metwali, N., Neilson, J. W., Maier, R. M., Gilbert, J. A., Holbreich, M., Thorne, P. S., Martinez, F. D., von Mutius, E., Vercelli, D., Ober, C., & Sperling, A. I. (2016). Innate immunity and asthma risk in Amish and Hutterite farm children. New England Journal of Medicine, 375(5), 411–421.

van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E. G., de Vos, W. M., Visser, C. E., Kuijper, E. J., Bartelsman, J. F., Tijssen, J. G., Speelman, P., Dijkgraaf, M. G., & Keller, J. J. (2013). Duodenal infusion of donor feces for recurrent Clostridium difficile. New England Journal of Medicine, 368(5), 407–415.

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Wunderlich, C. A. (1868). Das Verhalten der Eigenwärme in Krankheiten. Otto Wigand.

Yang, Y., Nguyen, M., Khetrapal, V., Sonnert, N. D., Martin, A. L., Chen, H., Kriegel, M. A., & Palm, N. W. (2022). Within-host evolution of a gut pathobiont facilitates liver translocation. Nature, 607(7919), 563–570.

Zhu, W., Gregory, J. C., Org, E., Buffa, J. A., Gupta, N., Wang, Z., Li, L., Fu, X., Wu, Y., Mehrabian, M., Sartor, R. B., McIntyre, T. M., Silverstein, R. L., Tang, W. H. W., DiDonato, J. A., Brown, J. M., Lusis, A. J., & Hazen, S. L. (2016). Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 165(1), 111–124.

The count held as later milk came in. At about 800 milliliters a day, a little over three cups, a baby takes in ten million to a hundred million bacterial cells. Older counts, which grew the bacteria on lab dishes, found about a hundred times fewer. Those cells are an early share of what NPR called an invisible universe (Figure 1).

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Figure 1. A tour of the microbes on and in a body. Drawn by Ben Arthur for NPR (2013). The video repeats an old estimate of ten microbial cells for every human cell; a 2016 recount by Ron Sender, Shai Fuchs and Ron Milo put it closer to one to one. Video and thumbnail: NPR, Standard YouTube License.

Which bacteria end up in a gut is not left to chance. In 1899, Henri Tissier, a children’s doctor at the Pasteur Institute in Paris, looked at babies’ stool under a microscope. In breastfed babies, one bacterium crowded out almost all the rest. Its rods often split at one end into a Y, so he named it bifidus, Latin for “split in two.” Today it is called Bifidobacterium. In bottle-fed babies, and in babies sick with diarrhea, it was far scarcer, and a mixed crowd took its place. The milk seemed to pick the winner.

Part of the answer is food. Human milk also carries a family of sugars the baby cannot digest. Most of them reach the colon, the last stretch of the gut, untouched. In 2006, Robert Ward, Bruce German and colleagues at the University of California, Davis, purified those sugars. They gave them to bacteria as their only food. One common gut bacterium could not live on them. Bifidobacterium infantis, one of Tissier’s Y-shaped bacteria, could. A year later, the team tested five kinds of Bifidobacterium, and infantis grew three times as dense as the rest. Every feed has two eaters: the baby, and the baby’s bacteria.

I have fed babies both ways. My first daughter had only breast milk. My second weighed more than 10 pounds at birth and was hungry before my milk arrived, so I breastfed her and we topped her up with formula. Her sister’s diapers had been mustard yellow. Hers were light brown, and they differed in texture, smell and how often they came. Tissier would have put both diapers under his microscope and counted the Y-shaped rods.

Bacteria settle wherever a body meets the outside world: in the gut, on the skin, in the mouth and nose, in the vagina. Each place grows its own crowd. Count every crowd, with the fungi and viruses beside them, and the whole is called the human microbiome.

Say you stand in the dairy aisle this week with a probiotic yogurt in one hand and a plain tub in the other. The probiotic costs twice as much. Its label promises billions of live bacteria for your gut, and the foil lid is cold under your thumb. Into the cart it goes, this week and most weeks after, fifty-two tubs a year. The label counts what goes in. It says nothing about the crowd already living there to meet it.

Milk feeds a baby’s bacteria at every meal, and a grocery aisle sells adults more. If bacteria keep arriving from the first swallow to the fifty-second tub, what are they to the body? Systems thinking answers a question like that by asking what else each part is connected to. In a gut, each kind of bacterium is fed, held back or crowded out by the others and by the body it lives in.

In 2024, Ziqi Ma and three colleagues, at Heidelberg University Hospital and Sun Yat-sen University, drew on more than 700 papers to answer that question. Their review sets out eight ideas for how microbes and a body fit together. The last four, on how the microbes work for health and why a body needs them, are part two of this series. This piece follows the first four. Biology now counts microbes the way it counts genes, all at once, and a count names the parts without the ties between them. The review opens on a map of where the microbes live.

Where the Crowds Live

Ma’s first figure pins a percentage to each place on a drawn human body where bacteria live. The gut gets 29 percent and the mouth 26, close behind. The skin, the airways and the urogenital tract share the rest. The review calls the gut the most densely populated of the five.

I traced those numbers to a pie chart the Human Microbiome Project published in 2009, then tried to replicate it. The project’s website listed every bacterium it had sequenced or queued for sequencing, with the body site each came from. The Internet Archive saved two earlier copies of that list, from March and April 2009. I counted both by the pie’s own rule: one strain, one count, sorted by body site. A strain is one line within a species, the way a beagle is one breed of dog.

Neither copy matched the pie, and the two did not match each other. In March, the gut held 58 percent of the list. By April it held 42, and in the pie, 29 (Figure 2). The list grew, and the shares moved with it. The shares measure what the project chose to sequence. When a probiotic label or a headline next quotes a share of the microbiome, the question to ask is what was counted.

Figure 2. The five percentages in Ma et al.’s 2024 review (squares), beside my recount of two earlier versions of the same list (circles and diamonds). Each marker is a share of the strains the Human Microbiome Project (HMP) had sequenced or queued for sequencing from that place, not a share of the bacteria living there. Squares from NIH HMP Working Group (2009), Fig. 3, as reprinted in Ma et al. (2024), Fig. 1; circles and diamonds counted for this piece from the project’s online strain lists, as saved by the Internet Archive. Chart drawn for this piece.

Where bacteria live takes a different count. Ma’s five shares look close to even. By cell count, they are far from it. Most of a body’s bacteria live in the colon. A single gram of stool, about the weight of a paper clip, holds some 90 billion bacteria, eleven times the number of people on Earth. The plainest test of what so many do is a birth with none waiting.

What Goes Missing

Doctors in Houston placed David Vetter inside a plastic bubble within seconds of his birth, in September 1971. He had severe combined immunodeficiency, an inherited disease that leaves the body almost no immune defense. His older brother had died of it as a baby.

Everything that went into the bubble was sterilized first: food, water, clothes, toys. Filtered air flowed in without stopping. His parents touched him through rubber gloves set into the plastic wall. In 1983, doctors gave him bone marrow from his sister, hoping it would build him an immune system. The marrow carried a virus no test had found. He died of a cancer it caused in February 1984, at twelve.

David is the closest thing to a germ-free person in the medical record, and he says little about what germs do for a body. His immune system had failed from birth, so any difference in him could come from the disease. For a cleaner answer, scientists turned to animals.

At the Lobund Laboratory at the University of Notre Dame, rats were delivered by cesarean section into sealed steel tanks and raised there on sterilized food, generation after generation. In 1963, Helmut Gordon, Bernard Wostmann and Edith Bruckner-Kardoss compared ten germ-free rats from the colony with twelve ordinary rats of the same stock. The two groups weighed the same. The germ-free hearts pumped about 30 percent less blood per minute for their weight, and not one germ-free rat reached the ordinary range. In a second set of rats, the germ-free ones also carried about a fifth less blood.

Later studies, gathered in Ma’s review, added to the list. Germ-free animals have a swollen cecum, the pouch where the small intestine meets the large one, about twice its usual size in rats. They have a smaller thymus, the gland that trains immune cells, and fewer immune cells in the gut wall.

The changes reach the brain. A tight seal of cells, the blood-brain barrier, keeps most of what travels in the blood out of the brain. In 2014, Viorica Braniste, Sven Pettersson and colleagues at the Karolinska Institute in Stockholm injected a blue dye into the blood of mice, three to a group. In ordinary mice, the dye stayed inside the blood vessels. In germ-free mice, it leaked into the brain itself. The leak starts before birth and lasts into adulthood. When the team gave adult germ-free mice the gut bacteria of ordinary mice, the seal tightened. Butyrate alone, a fatty acid that gut bacteria make from fiber, tightened it as far as in ordinary mice.

Ma’s team gathers these findings under one name: germ-free syndrome. Taking the microbes away does not leave a clean body. It leaves a body with missing parts. “A gut devoid of microorganisms,” they write, “cannot be considered a complete intestine.”

Germ-free syndrome is Ackoff’s definition of a system, run as an experiment. Each part can change how the whole behaves, but never alone. The mice lost the microbes in their gut, and the seal around their brains changed.

Anyone who has finished a course of antibiotics has run a small, short version of this experiment. In a Danish study, twelve healthy men took a mix of strong antibiotics for four days. Their gut bacteria took about six weeks to come back close to where they had been. Six months later, nine common species were still gone from most of the men.

In the weeks after a course, the question is what changed besides the infection it treated: digestion, appetite, a rash. The person to send this section to is a friend halfway through a course of pills. Whatever the missing microbes did, the rats and mice could not do it with their own genes.

Whose Genes Count

On a rosebush, an aphid that lacks the genes to feed itself presses its mouthparts into a stem and drinks. Sap is mostly sugar water. It holds too few of the amino acids an animal needs to build proteins, and the aphid cannot make them.

Bacteria called Buchnera live inside special cells in the aphid’s body and make the missing amino acids for it. The bacteria have lost so many of their own genes that they cannot live anywhere else, and the aphid cannot live without them. A mother aphid passes them straight into her eggs. Almost every aphid starts life with its bacteria in place.

People start differently. By most evidence, a human baby grows in the womb without live microbes. The first ones arrive at birth, from the mother’s skin, gut and birth canal, then from breast milk, from the father and from everyone who holds the baby. They keep arriving for life. By about age three, a child’s gut community settles into something close to an adult’s.

The bet on how many genes a person carries ended near 20,000. The bacteria in one gut carry far more. In 2010, the European MetaHIT team sequenced stool from 124 people. They counted 3.3 million distinct microbial genes, about 150 times the human count. Any two people differ in only about 0.1 percent of their own DNA, Ma’s team notes. The microbes may explain more of what sets one person apart. How much more, no one knows yet.

Ma and colleagues split a person’s genes into two sets. The innate genome is the one built from egg and sperm. It is inherited by fixed rules, and it does not change after birth. The adaptive genome is the set of genes the microbes carry. It is picked up over a lifetime. It changes with what a person eats, the drugs they take, where they live and who they live with. The innate genome changes over many generations. The adaptive genome can change in days (Figure 3).

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Figure 3. About 20,000 human genes against millions of microbial ones, and why food can change the second set but not the first, from The Washington Post (2021), with food and mental health reporter Mary Beth Albright. The mouse and fly studies it cites are early work. Video and thumbnail: The Washington Post, Standard YouTube License.

Living together is enough to share some of those genes. In 2023, Mireia Valles-Colomer and colleagues traced bacterial strains across more than 9,700 samples from people around the world. People in one home shared about 12 percent of their gut strains and 32 percent of their mouth strains. The longer they had lived together, the more mouth strains they shared. The samples show who shares strains. They cannot show who passed them to whom.

A new baby, a new partner or a new roommate starts that sharing under one roof. The question for a household is who brought what in. When a stomach bug moves through a home and skips one person, the germ was the same. The hosts were not.

Who the Host Is

In South Africa, Christina Gosmann and Douglas Kwon’s team tracked one germ, HIV, in 236 young women. They tested the women again and again. None had it at the start, and all were 18 to 23. Thirty-one became infected during the study.

The team had also sampled the bacteria in each woman’s vagina. Some women had a mixed community, with many kinds of bacteria and few Lactobacillus. Others had a community dominated by one species, Lactobacillus crispatus. The mixed group was more than four times as likely to become infected. Not one of the women dominated by L. crispatus became infected. The mixed communities came with more of the activated immune cells that HIV infects.

A study that follows people cannot settle what caused what. The women with mixed communities may have differed in other ways too, and the bacteria could be a marker as much as a cause. Animals can be tested more directly. In 1955, B. P. Phillips and colleagues placed Entamoeba histolytica, an amoeba that causes dysentery, into the guts of germ-free guinea pigs. The amoeba did no harm. Feed the guinea pigs one kind of common gut bacterium first, and the amoeba damaged the gut wall.

A cleaner test was run on a mosquito. Aedes aegypti carries dengue, a virus that brings fever, crushing joint pain and, in the worst cases, bleeding. Many insects carry a bacterium called Wolbachia inside their cells, but this mosquito normally does not. Scott O’Neill’s team at Monash University moved a strain of Wolbachia from fruit flies into Aedes aegypti. Inside the mosquitoes that carried it, the virus grew poorly. Like the aphid’s bacteria, Wolbachia passes from mother to eggs, so it can spread through a wild population on its own.

From 2017 to 2020, Adi Utarini and colleagues at Gadjah Mada University tested those mosquitoes in Yogyakarta, Indonesia. They split a part of the city, home to about 313,000 people, into 24 areas and released Wolbachia mosquitoes in half of them, chosen at random. Volunteers left buckets of water and mosquito eggs around the neighborhoods, and the eggs hatched into mosquitoes carrying the bacterium. In the areas that got them, dengue fell by 77 percent, and hospital stays for dengue by 86 percent. It was one trial, in one city. The mosquitoes were the same species, and the virus was the same virus. The bacteria living inside the mosquito changed how often it passed the virus on.

Whether a germ makes someone sick depends on the germ, on the person’s own genes and on the microbes already there. Ma calls the person and their microbes together a meta-host. Doctors have long asked why one germ makes one patient very sick and leaves another well, and why one transplant takes while another fails. Ma’s team points to the meta-host as part of the answer. The one person a stomach bug skipped at home was a different meta-host from the rest of the household. The crowd that person carried is one of three places to look for why. The host had always been a crowd, and part of that crowd lives in every human mouth.

What the Body Keeps in Check

On 17 September 1683, Antonie van Leeuwenhoek wrote to the Royal Society in London about his teeth. He was a cloth merchant in Delft who ground his own lenses. He scraped the white paste from between his teeth, thick as wet flour, and looked at it through one of his lenses. It was alive.

Some of the tiny animals darted through it “as a Jack or Pike does thro the water.” Others “spun about like a Top.” He kept his teeth “usually very clean,” he wrote, and still they were there. He looked at the teeth of two old men, one who lived soberly and one who drank brandy and wine every day, and found them there too.

Three centuries later, scientists still argue about what to call them. In 1992, the immunologist Velio Bocci, at the University of Siena in Italy, called the gut’s bacteria “the neglected organ,” and the label spread. In 2022, Alessandro Fucarino, Francesco Cappello and colleagues at the University of Palermo answered that the label does not fit. An organ is built from tissues that grow from the embryo, and microbes arrive from outside. In a 2026 essay, the microbial ecologist Allan Konopka points out that the right picture depends on the level someone looks from.

In their 2024 review, Ma’s team looks from the level of tissues. Next to the four kinds in biology textbooks, epithelial (the body’s linings), connective, muscle and nervous, they propose a fifth. They call it a “slave tissue,” a term borrowed from sociology, to say the body is in charge. This piece calls it a managed tissue.

The managing never stops, because bacteria left alone keep multiplying. More cells make more cells, a reinforcing loop that slows only when the food runs out. So the body sets limits of its own, and one of them can be seen under a microscope.

In 2008, Malin Johansson, Gunnar Hansson and colleagues at the University of Gothenburg, in Sweden, looked at the lining of the colon in five mice. It wore two coats of mucus, together about as thick as two human hairs. The outer coat was loose and full of bacteria. The inner coat, packed tight and stuck to the wall, held none. In mice bred without the main mucus protein, bacteria lay against the cells of the wall, and the colon became inflamed.

Mucus is one limit among several. Antibodies released into the gut keep microbes in their places. Proteins in the gut and in milk lock away iron and zinc that bacteria need to grow. Leeuwenhoek’s tooth cleaning in Delft belongs on that list. So do the milk sugars from the opening. Only some bacteria can eat them, so a mother’s milk helps choose which ones grow in her baby’s gut, as Tissier saw in Paris. The microbes help the body only while the body keeps them in check.

The same managing reaches the dinner plate. Onions, apples and whole-grain bread carry fiber, food the body cannot digest and many gut bacteria can, much as the milk sugars feed Bifidobacterium. When fiber runs short, some of those bacteria turn to the mucus coat instead (Figure 4). What goes on the plate tonight helps decide what the colon’s bacteria eat.

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Figure 4. Fiber as food for gut bacteria, and what hungry bacteria do to the mucus lining, from TED-Ed (2017): lesson by Shilpa Ravella, animation by Andrew Foerster. CC BY-NC-ND 4.0.

By the sink, a toothbrush with splayed bristles has been doing the managing twice a day.

A Closing Invitation. The milk in the opening fed two eaters at once. So did every meal and every dose in this piece: whatever reaches a body reaches its microbes too. Three ways to watch for the second eater.

1. Map who shares. From where you sit, picture what your home passes around: the toothbrush cup, the shared towel, the pillow, the spoon at dinner. People who live together share about a third of their mouth strains, and more the longer they stay. Who has lived beside you longest, and what crowd do you two now carry in common?
2. Trace the last bug. Think back to the last stomach bug that went through your home. Who caught it first, who caught it last, and who was skipped? The same germ had its chance at each of them. What else might the one who stayed well have been carrying?
3. Turn the tub over. At the store this week, pick up one probiotic yogurt or capsule box and read the back, the plastic cold in your hand. What does it count: bacteria made, bacteria alive, or bacteria that stay? Which crowd is already in your gut to meet them?

Tonight, somewhere, a baby feeds. Each swallow carries bacteria in, and sugars that only some of them can eat. Both eaters grow at every feed, and a scale weighs only one of them.

Where This Came From

The four ideas here are the first half of Ma’s eight; the order is this piece’s own. Ma’s review traces the lineage. Lynn Margulis called a host with its microbes a holobiont in 1991, and Richard Jefferson later named their combined genes the hologenome. The aphid fits that word well. Ma’s team argues that people do not, because contact is not inheritance, and so they split a person’s genes in two.

Intellectual Honesty Note. This piece describes what milk carries, not how anyone should feed a baby. The two daughters and their feeds are my own. The dairy aisle in the stakes paragraph is hypothetical. The squares in Figure 2 come from a 2009 Human Microbiome Project pie chart that counts bacteria sequenced or queued for sequencing. Ma’s text reads them as density. It also drops the pie’s blood (1 percent) and eye (0 percent) slices, so its five places add up to 99 percent. My recount (lists saved March 6 and April 10, 2009) groups body sites by name: gut and stomach under GI tract, vagina and urine under urogenital. Strains listed with no site, 1 and 4 percent, count in the totals but get no marker. No later copy of the list was saved, so the pie itself could not be recounted. Ma et al. (2024) is a narrative review, and its ideas are proposals, not settled findings. Tissier’s findings are reported from later accounts; his 1900 thesis was not opened. The germ-free results come from rodents and guinea pigs. The mucus result is from mice, and “two human hairs” is this piece’s gloss of its 150 micrometers. The Entamoeba result is reported from summaries of the paper, which was not opened. Leeuwenhoek’s words are from the Royal Society’s English abstract of his letter, printed in 1684. Ma’s team counts eight ideas, though one of their own figures lists seven; part two folds the eighth, cell-microbe co-ecology, into its set-point section.

References

Albright, M. B. (2021, October 30). What is the gut microbiome? [Video]. The Washington Post. YouTube. https://www.youtube.com/watch?v=d-Ln9NNj2KY

Boix-Amorós, A., Collado, M. C., & Mira, A. (2016). Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Frontiers in Microbiology, 7, 492.

Bocci, V. (1992). The neglected organ: Bacterial flora has a crucial immunostimulatory role. Perspectives in Biology and Medicine, 35(2), 251–260.

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