10% Human How Your Body's Microbes Hold the Key to Health and Happiness - Collen, Alanna

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• The prologue describes how the author contracted a tick-borne infection while conducting fieldwork in a Malaysian rainforest that took years to diagnose and treat. The long-term antibiotics left the author feeling like their digestive system and ability to fight infections was compromised.

• The introduction states that modern research is revealing humans are only 10% human, with the other 90% made up of microbes. The human microbiome - the collection of microbes in and on the human body - plays a major role in health.

• The author conducted their own microbiome sequencing through the American Gut Project to examine the impact of antibiotics. It showed their microbial diversity was lower than average, with 97% of bacteria from two main groups rather than the typical 90%.

• The contents section lists 13 chapters that will explore the emerging evidence that disruptions to the human microbiome underlie many modern health issues like gastrointestinal disorders, allergies, autoimmune diseases, obesity, and even mental health conditions.

• The prologue sets up the author’s personal journey of investigating their own health issues and microbiome after a life-changing tropical infection and prolonged antibiotic use.

• The author embarked on learning more about the bacteria that live inside their body (the microbiome) and how it interacts with human health and genes.

• They took antibiotics in the past which likely disrupted their microbiome. By sequencing their bacteria, they hoped to understand how this impacted their health issues like allergies and infections.

• They resolved to alter their lifestyle and diet to support a healthier, more diverse microbiome. Specifically focusing on the needs of their microbes rather than just themselves.

• The goal was to sequence their microbiome again after these changes to see if it improved. Hoping this would both reveal the impact of their efforts and unlock better health long-term by strengthening their relationship with their microbial cells.

• Overall, the author wanted to better understand the role of microbes in human health and pass on a healthier microbiome to any future children through enriched lifestyle habits supporting a balanced inner microbial community.

• Many animal species have beneficial relationships with microbes that live in and on their bodies. For example, the Hawaiian bobtail squid houses bioluminescent bacteria in an organ that acts as a form of camouflage, while cows rely on microbes in their stomach to break down fibrous plant matter.

• The human appendix was long thought to be a vestigial organ with no function. However, it is actually packed with immune cells and houses beneficial gut microbes. It acts as a safe harbor for these microbes, recolonizing the gut after infections.

• Appendicitis became much more common in the late 19th/early 20th centuries, coinciding with changes in diet, hygiene, and sanitation in industrialized societies. Keeping the appendix may help protect against recurring gut infections and certain diseases. Rather than being useless, the appendix serves an important role in maintaining a healthy microbiome.

• The human body plays host to diverse microbial communities that live in different habitats across the skin, mouth, gut, and other areas. These microbes perform important functions that benefit the host.

• DNA sequencing techniques have revealed the vast diversity of microbial species that inhabit the human body. Different body sites harbor distinct communities composed of species unique to individuals.

• Studies using germ-free mice have shown that the presence of gut microbes shapes the development and function of the digestive system. Microbes influence processes like food digestion and energy extraction from nutrients.

• The human microbiome provides protection against pathogens through competitive interactions on body surfaces. Unique microbial communities inhabit different niches of the skin, mouth, and other habitable areas.

• Researchers have characterized microbial communities across 18 body sites as part of the Human Microbiome Project. This work revealed each person harbors a distinct fingerprint of microbial species, while maintaining similar ecosystem functions.

• The human gut is home to trillions of microbes from thousands of species. Different areas of the gut have unique microbial communities based on environmental factors like pH levels, oxygen availability, and food sources.

• Samples from stool provide insights into the overall gut microbiome as stool contains mostly bacteria and fibers that have passed through the digestive tract.

• The small and large intestines contain the highest densities of microbes, reaching billions to trillions per milliliter. Key areas include the cecum and colon.

• Gut microbes play important roles like producing vitamins, shaping intestinal walls, and extracting energy from foods. The human body has formed a symbiotic relationship with these microorganisms.

• Studies like the Human Microbiome Project aim to understand how microbial imbalances may relate to diseases and health conditions both within and beyond the gut. The microbiome is increasingly seen as an important factor in human biology, evolution, and individuality.

• In the 16th-18th centuries, smallpox spread widely due to exploration and increased mobility, killing up to 400,000 Europeans per year. Variolation helped reduce deaths and Edward Jenner’s vaccine in 1796 brought further relief.

• In the early 20th century, infectious diseases were a major cause of death in developed countries like pneumonia, tuberculosis, and diarrhea. They accounted for 1/3 of all deaths in the US. Life expectancy was only 31 years globally and 50 years in developed nations.

• Medical advances like vaccination, hygiene practices, antibiotics, and improved living standards led to dramatic increases in life expectancy over the 20th century. Average global life expectancy doubled to 66 years by 2005.

• Vaccination trains the immune system to fight pathogens without suffering disease. Herd immunity through mass vaccination has eliminated or nearly eliminated many infectious diseases in developed nations. Smallpox was eradicated globally by the 1970s saving millions of lives and billions of costs.

• Worldwide vaccination programmes have dramatically reduced cases of infectious diseases like polio, measles, and rubella. Polio cases declined from 350,000 annually to just 223 cases in 3 countries by 2012. Vaccines have prevented half a million deaths and 10 million cases of paralysis from polio.

• In the 19th century, hospitals spread infections due to lack of hygiene and the germ theory of disease not being understood yet. Doctors carried infections from autopsies to patients, leading to high mortality rates for women giving birth in hospitals.

• Ignaz Semmelweis discovered handwashing with chlorinated lime solution dramatically reduced mortality rates, but he was ridiculed by his contemporaries. The germ theory later validated his findings.

• Joseph Lister adopted antiseptic practices like carbolic acid which reduced surgical mortality rates. This established hygienic medical practices.

• John Snow traced a 1854 cholera outbreak in London to a water pump on Broad Street, discovering cholera was water-borne. This was an early application of evidence-based disease investigation and eliminated cholera in Soho.

• These innovations in vaccination, hygiene, and identifying disease transmission routes greatly reduced morbidity and mortality from infectious diseases in developed nations.

• In the 19th century, major advances were made in public health through epidemiology (understanding disease patterns), water sanitation with chlorination, and vaccination. By the early 20th century, 10 diseases could be prevented through vaccination.

• During WWI, Sir Alexander Fleming noticed that the penicillin mold inhibited bacterial growth in his lab. This discovery led to the development of antibiotics over decades of research. By the 1940s, penicillin was mass produced andrevolutionized medicine by treating infections.

• Common now but rare historically, modern “21st century illnesses” include allergies, autoimmune diseases, digestive issues, mental health problems, and obesity. Allergies now affect nearly half of people in developed nations. Autoimmune diseases impact around 10% of populations.

• The rise of these chronic conditions is abnormal and unexpected given medical advances against infectious disease. For example, asthma now affects 1 in 4 children compared to very rarely in the early 20th century. Food allergies have also increased dramatically. This suggests environmental factors are influencing the immune system in new ways.

• Rates of various chronic conditions like type 1 diabetes, multiple sclerosis, celiac disease, inflammatory bowel diseases, obesity, autism, depression and anxiety have risen significantly over the past century.

• This rise cannot be explained by genetics alone, as human evolution does not occur that rapidly. Gene variants also usually provide advantages to spread through natural selection.

• The increase in these illnesses is not normal and suggests something in our modern environment may be influencing disease risk.

• A variety of factors have changed in recent decades like nutrition, exercise, lifestyle and environmental exposures. Determining which causal changes require further scientific evaluation.

• While genetics play a role, the environment is also critical in determining disease risk and traits like height. Changes in our environment may therefore be contributing to rising rates of chronic illnesses.

• Understanding the causes is important to address these non-infectious diseases that have replaced many infectious illnesses in industrialized countries.

So in summary, it notes the abnormal rise of many chronic conditions and argues our modern environment, not just genes, must be influencing this change in disease patterns over the last century.

• The passage explores possible connections between modern illnesses like obesity, allergies, autoimmune diseases, and gut/mental health issues.

• Two main themes emerge - dysfunction of the immune system and gut. The gut contains most of the body’s immune cells, creating an important link between gut and immune health.

• Using epidemiology, the passage examines patterns in terms of where illnesses are occurring (Western countries), who they affect (wealthier populations), and when they emerged (late 20th/early 21st century).

• Higher wealth and standards of living are strongly correlated with increased risk of these modern illnesses. As developing countries grow wealthier, related conditions are spreading there as well.

• Within countries, the wealthy initially have higher risk but this inverts - the poorest populations in developed countries now face greater chronic health problems.

• The passage then examines demographic patterns in terms of age, race, and sex of those affected to gain further clues about underlying causes. In summary, it uses epidemiological analysis to link modern illnesses to environmental changes associated with advanced economies and prosperity.

• Many chronic diseases and health conditions are on the rise, particularly in developed countries, affecting both children and adults. This includes conditions like food allergies, asthma, autism, autoimmune diseases, obesity, and some cancers.

• Unlike in the past, many of these illnesses are not simply diseases of old age. Many manifest early in life, in childhood and early adulthood.

• Race does not appear to be a major factor - while some conditions are more common in certain ethnic groups, this seems to be due more to environmental/location factors than genetics. Studies of migrant populations support this.

• Women are often more susceptible than men, likely due to stronger immune systems which can result in overreactions. However, some conditions like autism are more male-dominant.

• The rise and spread of these modern chronic illnesses started in Western countries in the 1940s-1950s. This suggests something changed around that time period that influenced disease development and prevalence on a large scale.

• In summary, these “twenty-first century illnesses” are chronic conditions connected to immune dysfunction that began affecting populations, especially in the West, in significant numbers starting in the mid-20th century.

The passage discusses garden warblers, small migratory birds that undergo rapid weight gain before long-distance migrations. Researchers were puzzled as to how the birds could gain so much weight (doubling in size) in a short time just by eating more, since calorie intake did not fully account for the weight gain. Captive warblers also gain and lose weight seasonally without making the migration.

This raises questions about whether human weight gain can fully be explained by calories in versus calories out. The story then shifts to Dr. Nikhil Dhurandhar, an Indian physician frustrated by failures to treat obesity through dieting. A virus was killing chickens and making them gain weight. Dhurandhar wondered if a virus could also be contributing to human obesity.

The scale of rising human obesity levels worldwide in recent decades is unprecedented in our species’ history. Our bodies have fundamentally changed in just 60 years from a lean physique to being encased in excess fat. The causes of this dramatic shift are still being debated.

• Nauru, a tiny country with only 10,000 people, has the highest rate of obesity in the world. Just 700 people are a healthy weight. Other South Pacific islands and Middle Eastern states also have high obesity rates.

• In Western countries, obesity has become common enough that lean people are now the minority. About 2/3 of adults in Western nations are overweight and 1/2 are obese. The US ranks 17th globally for overweight rates, the UK ranks 39th. Up to 1/3 of children in Western nations are overweight, with half being obese.

• Obesity has increased dramatically over the last 50-60 years. The average person in Western nations has gained about 1/5 of their body weight over the past 50 years alone. Today, many people would be significantly lighter if they lived in the 1960s without trying.

• Despite billions spent on dieting and exercise, obesity levels continue to rise. Genetic and metabolic factors alone cannot explain the epidemic, as genetics and metabolism have not significantly changed. The environment - diets and lifestyles - must be playing a role in how genes and metabolism function.

• Gastric bands and bypass surgeries, which alter digestion, seem to be the most effective treatment currently. This suggests weight management is far more complex than simply calories in vs. calories out. Gut microbes may also influence obesity and conditions like IBS.

• Irritable bowel syndrome (IBS) is a condition that causes diarrhea, constipation or both, making daily life unpredictable. It affects about 1 in 5 people in the West.

• The exact cause of IBS is unclear, though it seems to involve an imbalance or “dysbiosis” of the gut microbiome. Factors like infections, antibiotics, diet and stress can disrupt the normal gut bacteria balance.

• Evidence suggests antibiotics and infections that cause diarrhea but then go away (like food poisoning) may lead to long-lasting changes in the gut microbiome and IBS symptoms. About 1/3 of IBS patients link onset to a past infection.

• Having an abnormal or unstable gut microbiome composition compared to healthy people has been found in many IBS patients. Differences correlate with symptom types like bloating or pain.

• It’s plausible that IBS results from irritation in the gut caused by the wrong bacterial balance, though the mechanisms are still being studied. The gut may become inflamed in response.

• Imbalances in gut bacteria have also been linked to weight gain and obesity. Studies in germ-free mice have shown colonizing them causes significant weight increase even with less food intake.

• Studies found that the microbes in our gut (microbiota) help us extract more calories and nutrients from our food through a second round of digestion. This suggests the microbiota plays a role in how many calories we absorb from what we eat.

• Ruth Ley found that obese mice had a different ratio of gut bacteria (more Firmicutes, fewer Bacteroidetes) compared to lean mice. She found the same ratio in obese versus lean humans.

• Peter Turnbaugh transferred gut microbes from obese mice to germ-free mice. The recipient mice gained fat, showing microbes can cause obesity. Microbes from lean mice did not have this effect.

• Turnbaugh calculated microbes from obese mice extracted 2% more calories from food than microbes from lean mice. Over time, this small difference can lead to substantial weight gain.

• The microbiota determines how many calories we extract from food by helping to break down nutrients in the large intestine. Different microbes specialize in different nutrients.

• The microbes can influence our genes to store more energy as fat. They benefit from a host that maintains a stable fat supply. So the microbiota plays a role in both energy extraction from diet and how our bodies process and store that energy.

• Nikhil Dhurandhar had the hypothesis that viruses could cause obesity in humans, challenging the idea that obesity is solely due to lifestyle factors like overeating and lack of exercise.

• He wanted to study an Indian virus he believed caused obesity in chickens, but the US would not allow importing it. So he and Professor Richard Atkinson chose to study Adenovirus 36 (Ad-36), a common human virus, on chickens.

• Dhurandhar infected some chickens with Ad-36 and others with a different virus as a control. They observed whether Ad-36 would cause the chickens to gain weight, as the Indian virus did.

• If Ad-36 also caused obesity, it would suggest obesity could be an infectious disease rather than just a willpower issue, and potentially even contagious.

• Maps of the US obesity epidemic spreading over time resemble how infectious diseases spread. One study also found social connections linked to obesity spreading between individuals, like an infection.

• Dhurandhar was challenging mainstream views by proposing infections like viruses could underlie the obesity epidemic, not just lifestyle and personal choices. He was taking a risk to further this unconventional hypothesis.

• Researchers have found evidence that viruses and gut bacteria may contribute to obesity by altering how the body stores and regulates energy.

• Dhurandhar discovered that virus Ad-36 caused chickens and marmosets to gain weight by influencing their energy storage processes, rather than causing them to eat more. Studies found higher rates of Ad-36 antibodies in obese humans.

• Cani hypothesized that “obese” gut bacteria were causing inflammation in fat tissue and preventing new fat cell formation in obese people. This led to overfilling of existing fat cells.

• LPS from gut bacteria was found to trigger this inflammatory response. The gut bacterium Akkermansia protects the gut lining and prevents LPS leakage, correlates with lower BMI. Supplementing Akkermansia in mice reduced LPS, improved fat cell formation, and caused weight loss.

• This research suggests obesity is not always simply due to overeating and underactivity, but can involve dysfunctional energy regulation influenced by microbes like viruses and gut bacteria. Approaches focused solely on diet and exercise have had limited success, indicating other factors may be involved.

• Gastric bypass surgery not only reduces stomach size, but also dramatically alters gut microbiota composition within a week, switching it from an “obese” profile to a “lean” one. This microbiota change, not just portion control, seems to drive weight loss.

• Transporting the microbiota from bypass surgery mice into germ-free mice also causes weight loss, showing the microbiota change is responsible.

• The surgery reroutes nutrients in a way that shifts bacterial species, altering energy regulation via the new “lean” microbiota.

• Microbes are showing obesity has more causes than just eating and exercise - gut microbes impact how the body extracts and stores energy from food.

• Understanding microbiota dynamics may help address the root causes of obesity beyond superficial calories in/out explanations. Microbes linked to health, weight, and other important factors.

• Andrew initially seemed to benefit from antibiotics for an ear infection, but then his behavior deteriorated rapidly. He became withdrawn, irritable, and developed bizarre behaviors like walking on his toes.

• His GI symptoms also worsened with increased diarrhea, mucus, and undigested food. Tests ruled out ear infections as the cause. Removing cow’s milk helped his ears but not his behavior.

• By age 25 months he was diagnosed with autism. His mother Ellen did not accept this diagnosis, convinced he was fine earlier.

• Ellen began researching, learning medical literature. She developed a hypothesis that antibiotics killed good gut bacteria in Andrew, allowing the bacterium Clostridium tetani to take hold in his gut.

• She believed the neurotoxin produced by this bacterium then traveled to his brain, affecting his development and behavior.

• Blood tests surprisingly showed extremely high levels of immunity to tetanus in Andrew, supporting possible previous C. tetani infection.

• Ellen believed this infection and toxin exposure, brought on by the antibiotics, may have caused Andrew’s autism symptoms rather than a genetic or lifelong condition.

• Ellen Bolte theorized that her son Andrew’s autism was caused by a Clostridium tetani infection in his gut, not his brain. She believed the neurotoxin produced by C. tetani traveled from his gut to his brain via the vagus nerve.

• Ellen approached over 30 doctors with her hypothesis but was dismissed at first. However, through extensive research, she found evidence supporting how C. tetani could infect the gut and affect the brain in this way.

• Eventually a doctor, Dr. Richard Sandler, agreed to an 8-week antibiotic trial for Andrew to treat the alleged C. tetani infection. Tests were done before and behavioral observations made during the trial.

• During the trial, Andrew showed remarkable improvements in behaviors, language, potty training and more. This provided evidence supporting Ellen’s gut-brain hypothesis for autism.

• Renowned microbiologist Dr. Sydney Finegold then helped expand the antibiotic trial to 11 more children with similar improvements, strengthening the case that gut microbes could be responsible for autism in some cases.

• In 2001, a study looked at the gut microbes of 13 children with autism and 8 healthy children. It found that autistic children had on average 10 times as many Clostridium bacteria in their guts, supporting Ellen Bolte’s hypothesis that gut microbes may play a role in autism.

• The Toxoplasma parasite, which infects up to 84% of women in some areas, has been shown to alter human behavior and personality. It makes infected men less agreeable and women more trusting. Both men and women also show slower reactions and reduced concentration when infected.

• Infection with Toxoplasma has been linked to increased risk of traffic accidents. It has also been implicated in mental health conditions like schizophrenia, OCD, ADHD and Tourette’s syndrome.

• Studies transplanting gut microbes between anxious and relaxed mouse breeds found it could transfer traits - anxious mice becoming calmer with relaxed mouse microbes, and vice versa. This suggests gut microbes may influence personality.

• Mice without any gut microbes are less social, while normal microbiota makes mice more friendly and social. Gut microbes may even affect attraction and mate selection. Overall, research increasingly points to gut microbes playing a role in behavior, personality and mental health.

Male sac-winged bats produce scented secretions in wing pouches to attract mates. The secretions contain urine, saliva, and semen, which cultivate beneficial bacteria that release sex pheromones. Similarly, fruit flies’ gut microbiota can influence their sex pheromones and cause populations separated by diet to refuse mating. Humans’ skin and mouth microbiota may also influence sex pheromones and partner choice through scent and kissing. Introducing beneficial bacteria to humans through food or supplements has shown promise in improving mood by increasing levels of the neurotransmitter serotonin, either directly or by modulating the immune system. The vagus nerve, connecting the gut and brain, may also mediate positive effects of gut bacteria on mood and depression treatments. In general, microbes play an underappreciated role in animal behavior and well-being through biochemical signaling pathways.

• Adding an electrical pacemaker to the vagus nerve can boost mood by stimulating nerve activity. Under normal circumstances, chemicals called neurotransmitters produced in the body stimulate nerve impulses.

• The gut microbiota also produce chemicals that act as neurotransmitters, stimulating the vagus nerve and communicating with the brain to influence mood. This acts as a natural stimulator of the vagus nerve.

• One hypothesis is that bacteria produce these chemicals to control behavior and benefit themselves by promoting behaviors like eating foods they feed on.

• Conditions like depression, ADHD, OCD, bipolar disorder and others involve immune system overactivity and inflammation. Probiotics can reduce inflammation and its impact on mood and behavior.

• In autism, the altered gut microbiota may trigger immune system overactivity, releasing chemicals called cytokines that influence brain development and behavior. Certain bacteria like Clostridium bolteae have been linked to autism.

• Experiments showed that injecting the chemical propionate, produced by certain bacteria, directly into rats’ brains caused autism-like behaviors. It also induced inflammation in the brain. This suggests gut bacteria and their chemical products may contribute to autism symptoms.

• Microbes in the gut, known as the microbiota, can produce compounds that influence brain functions and behaviors. Some research suggests changes in the microbiota could be linked to autism and other neuropsychiatric disorders.

• Researchers like Derrick MacFabe and Emma Allen-Vercoe are investigating how compounds produced by gut microbes could travel to the brain and influence things like memory formation, obsessions, food interests, etc.

• Allen-Vercoe takes a holistic approach using a simulated gut environment called “Robogut” to study the microbial ecosystem and metabolites it produces, rather than isolating individual bacteria.

• Ellen Bolte published a hypothesis in 1998 linking autism to invasion of the gut by Clostridium tetani bacteria after antibiotics disrupt the normal microbiota. Her daughter Erin is now working with Allen-Vercoe to test aspects of this hypothesis using Robogut.

• The research aims to understand what changes in the autistic gut when antibiotics or certain foods like gluten/casein are added, to shed light on the role of microbiota in autism and other neuropsychiatric conditions. The hope is this can help prevent or treat such illnesses.

• The hygiene hypothesis, proposed by David Strachan in 1989, suggested that allergies have increased in developed nations due to improved hygiene and fewer infections. The under-stimulated immune system becomes “overactive” and attacks harmless substances.

• Strachan’s study found children with more siblings (a source of infections) were less likely to have hay fever. He proposed early-life infections help train the immune system to not overreact.

• The idea gained support as allergies rose alongside hygiene improvements. Developing nations with more infections had fewer allergies.

• The hypothesis was extended to suggest parasites like worms also kept the immune system occupied, and their absence now leaves it “overstaffed.”

• However, evidence for direct links between specific infections and lower allergies was inconsistent or had alternative explanations. Strachan himself found early-life infections did not reduce allergy risk.

• While family size correlations held up, the theory of exactly how early infections might prevent allergies via immune cell divisions was an oversimplification. Clear evidence remained elusive.

• The simplistic division of the immune system into Th1 and Th2 responses does not accurately describe how pathogens are fought. Both Th1 and Th2 cells are involved against most pathogens.

• Rising rates of autoimmune diseases like diabetes and multiple sclerosis involve excess Th1 responses, not Th2 as the hygiene hypothesis suggests.

• The human body contains trillions of bacteria in the microbiome that could be targets for the immune system, yet it tolerates these microbes instead of attacking them.

• The hygiene hypothesis that less infections lead to more allergies does not fully explain the evidence. A rethinking is needed to account for the role of the microbiome in immune regulation.

• Humans have a symbiotic relationship with their resident microbes that has evolved over millions of years. The microbiome is crucial for health and development, and the immune system has learned to accommodate these beneficial microbes.

• Disruption of the microbiome through modern hygienic lifestyles may impair proper immune development and regulation, contributing to rising inflammatory and autoimmune diseases. The evolution of host-microbiome partnerships underscores their interdependent relationship.

• Evolutionary biologists debate what exactly natural selection acts upon - the individual, the group, or genes. Richard Dawkins argued that selection ultimately acts upon genes as they determine an individual’s likelihood of reproducing.

• Host organisms and their microbiomes have also coevolved together as holobionts. Eugene and Ilana Rosenberg proposed that natural selection can act upon the host genome and microbiome combined, known as “hologenome selection.”

• The human immune system did not evolve in isolation but with the presence of microbes. Being raised germ-free disrupts the normal development and balance of the immune system.

• David Vetter, known as the “Bubble Boy,” lived his life isolated from microbes due to a immune deficiency. Studies on him provided limited insights into the role of microbiome on health as he was not truly germ-free.

• Germ-free animals have abnormal digestive systems and underdeveloped immune systems compared to normal animals. They are highly susceptible to infections that normal animals can resist, showing the importance of microbiome for immune system development and health.

Treating mice with antibiotics makes them unable to fight off the flu virus if it enters their noses, as their immune cells do not produce enough antibodies to prevent infection. While antibiotics treat infections, they can leave the body open to other infections by shifting the normal balance of gut microbiota.

Antibiotics kill anaerobic bacteria in the gut, changing the composition of microbiota. This interferes with immune system genes, reducing mucus production and exposing the gut lining. If microbes or chemicals cross into the bloodstream, the immune system responds.

Studies link long-term antibiotic use to increased risk of colds and infections. Another found children given antibiotics before age 2 were nearly twice as likely to develop asthma, eczema and hay fever as more courses of antibiotics increased risk.

While hygiene lowers infections, it also alters gut microbiota colonization in newborns. Lower microbiota diversity in “ultra-hygienic” Swedish babies linked to higher allergy rates later. The “Old Friends” hypothesis proposes our coevolved microbiota, rather than infections alone, guide proper immune development. Exactly how the immune system identifies friend from foe microbes remains unclear, but regulatory T cells help balance inflammatory responses.

• Immune system regulation is normally controlled by Tregs (regulatory T cells), which suppress inflammatory immune responses. The microbiota (gut bacteria) is able to manipulate Treg numbers to control the immune system and ensure its own survival. Loss of microbiota diversity reduces this regulatory effect.

• Bacteroides fragilis, a common gut bacterium, produces polysaccharide A (PSA) which triggers the activation of Tregs. This converts the immune response from pro-inflammatory to anti-inflammatory, preventing attacks on the microbiota.

• Cholera is caused by Vibrio cholerae bacteria which colonize the intestine. They communicate via quorum sensing to determine when their numbers are high enough to initiate release of toxins like zonula occludens toxin (Zot). Zot loosens intestinal cell junctions, causing severe diarrhea which flushes the bacteria out to infect new hosts.

• Zonulin is a human protein similar to Zot which also regulates intestinal permeability. Under microbiota imbalance, the immune system releases zonulin, making the gut lining “leaky” and allowing foreign substances to enter the bloodstream. This link between the microbiota, immune system and intestinal barrier function is still being scientifically studied.

• The concept of “leaky gut syndrome” is viewed skeptically by the medical and scientific establishment due to a lack of strong evidence. However, some alternative health practitioners promote it as an explanation for various health issues.

• The theory is that a “leaky” or permeable intestinal wall allows toxic molecules like undigested food and bacteria to pass into the bloodstream, triggering whole-body inflammation and various diseases.

• Research suggests conditions like celiac disease, type 1 diabetes, obesity, depression, and others involve increased intestinal permeability and chronic inflammation.

• The protein zonulin has been found to regulate intestinal permeability. High levels are seen in celiac disease and may play a role in type 1 diabetes as well.

• Excess lipopolysaccharides (LPS) from gut bacteria have been linked to obesity, inflammation, and mental health issues when intestinal permeability rises and allows LPS into the bloodstream.

• While not proven to be the cause of all diseases, evidence is growing that a leaky gut and chronic inflammation may underlie many modern health problems. More research is still needed to fully evaluate the concept.

• Places like remote parts of Papua New Guinea and Indonesia do not seem to have issues with acne, even among teenagers, unlike in industrialized societies where over 90% of people experience acne at some point.

• The conventional explanation for acne (overactive hormones causing excess sebum production and provoking an immune response involving P. acnes bacteria) does not fully hold up, as hormone and bacteria levels do not perfectly correlate with acne severity.

• New research suggests acne may be more of an immune-mediated inflammatory condition, with the immune system becoming oversensitive to normally harmless bacteria like P. acnes. Antibiotics may help acne by altering the gut microbiome and immune function rather than directly targeting P. acnes.

• An unhealthy microbiome is linked to other inflammatory conditions like IBD and cancer through various mechanisms like increased intestinal permeability, production of toxic compounds, and dysregulated immune responses against commensal bacteria.

• Maintaining a diverse, beneficial microbiome may be more important for immune and overall health than avoiding germs, as suggested by the “Old Friends” hypothesis versus the “hygiene hypothesis.” Western lifestyles and antibiotic overuse have disrupted our microbial communities.

• Antibiotics have historically been widely used in livestock to promote faster growth and increased production. Estimates suggest up to 70% of US antibiotics are used this way in animals.

• This widespread use of antibiotics in livestock raised questions about whether they may also promote weight gain in humans. Nicholson speculated antibiotics could be a contributing factor to the global obesity epidemic.

• Losing weight is very difficult for most people and keeping it off long-term is especially challenging. This has led some to question if obesity should be viewed as more of a complex disease rather than just an energy imbalance issue.

• The theory is that if antibiotics can boost livestock growth by 10% per day, they may also influence human metabolism and make weight gain easier and weight loss harder. This could help explain aspects of the obesity epidemic that are difficult to account for by individual behavior alone.

• Antibiotic use is now extremely widespread worldwide. Developed countries in particular have seen antibiotic prescription rates skyrocket since their introduction, especially for children. Half of childhood antibiotic use may be unnecessary or inappropriate.

• Around 55% of antibiotic prescriptions given out in a year are unnecessary according to some estimates. Both patient expectations and doctor fears of misdiagnosis contribute to overprescription.

• Taking unnecessary antibiotics promotes the development of antibiotic resistance. Untreated minor illnesses in many people leads to treatment failure in few people with serious illnesses down the road.

• Examples given include needing to treat over 4,000 sore throat cases to prevent complications in one person, and 50,000 children for ear infections to prevent one case of mastoiditis.

• Widespread antibiotic use has led to resistant strains like MRSA and increased cases of C. difficile infection, which can have severe and sometimes fatal consequences.

• C. difficile normally does not cause issues but antibiotics disrupt the gut microbiota balance, allowing C. difficile to flourish. This highlights antibiotics’ collateral damage to beneficial gut bacteria.

• In addition to antibiotic resistance, overuse can directly harm individuals through side effects like rashes and diarrhea in about 1 in 21 people treated unnecessarily.

• Both resistance and collateral damage stemming from antibiotic overuse combine to threaten our ability to effectively treat bacterial infections. More judicious use of antibiotics is needed.

• Antibiotics often cause temporary diarrhea and bloating as they disrupt the gut microbiome (dysbiosis). However, researchers found that some bacteria like Bacteroides species may fail to fully recover their diversity and composition even years after antibiotics.

• Short antibiotic courses of just 5 days still have a profound and lasting impact on the gut microbiome, changing species diversity and composition for weeks. The impact on infants can be even more dramatic.

• Multiple studies have found that different common antibiotics lead to long-term changes in the gut microbiome composition in different ways. Even low doses can have effects that outlive the original illness.

• Early correlations between the rise of antibiotics in 1944 and increases in diseases like obesity, allergies and autism in the following decades are notable but not definitive on their own.

• However, older studies in the 1950s found that antibiotics unexpectedly promoted weight gain in babies, children and young adults. This connection to weight gain was later neglected despite the obesity epidemic.

• Newer research confirms antibiotics can preferentially expand resistant gut bacteria like Lactobacillus reuteri that promote weight gain in mice and humans. Effects vary depending on the antibiotic and individual.

• Gut bacteria play a role in metabolism and weight regulation, so prolonged antibiotic impacts on the microbiome are a plausible mechanism for their association with increased chronic disease risk.

• Studies have shown that children who are given antibiotics in the first 6 months are more likely to become overweight. One study found 40% of overweight kids received antibiotics in the first 6 months vs 13% of normal weight kids.

• Researchers administered low doses of penicillin to pregnant and nursing mice. The male mice exposed grew faster and as adults both males and females were heavier with more fat mass.

• Mice given penicillin and a high-fat diet gained significantly more fat than those just on a high-fat diet, showing antibiotics amplified the effect of an unhealthy diet.

• Transferring the altered microbiota from antibiotic-treated mice to germ-free mice induced similar metabolic changes, indicating it was the changed microbiome, not the drugs directly, causing weight gain.

• While stopping antibiotics allowed microbiota recovery, metabolic effects of treatment persisted. This suggests antibiotic exposure early in life can cause permanent metabolic changes.

• Antibiotics are commonly used in livestock and their residues have been found in meat and vegetables fertilized with manure, thus exposing humans even without direct antibiotic use.

• The obesity epidemic and rise of conditions like autism have coincided with increased antibiotic use in medicine and agriculture since the 1950s, suggesting antibiotics may be an underlying cause by disrupting the microbiome.

• Studies have found a link between antibiotic use in young children and an increased risk of autism, allergies, and autoimmune diseases like type 1 diabetes. Children given antibiotics before age 2 were twice as likely to develop asthma, eczema or hay fever.

• The connection between infections and autoimmune diseases like diabetes is not clear. While doctors see diabetes develop after infections, infection rates have declined while diabetes has risen. Antibiotics are often prescribed for viral infections unnecessarily. Antibiotics themselves may be triggering autoimmune responses.

• Use of the antibiotic minocycline increases lupus risk by 2.5 times overall and 5 times for women. Antibiotic use has also been linked to increased multiple sclerosis risk.

• Antibacterial soaps and cleaners do not provide extra benefits over regular soap. They claim to kill 99.9% of bacteria based on lab tests, not real-world use. Many bacteria can form resistant spores. Antibacterial chemicals have largely not been tested for safety effects.

• Overall, overuse of antibiotics and antibacterial products is contributing to disruption of the microbiome and increased disease risks through immune system impacts. More testing of chemical safety effects is still needed.

• Triclosan is a common antibacterial chemical found in many household cleaning and personal care products. It has come under scrutiny due to health and environmental concerns.

• Studies show triclosan is no more effective than regular soap, but it contaminates water supplies and disrupts ecosystems when washed down drains.

• Triclosan is absorbed into human bodies and can be found in breastmilk, umbilical cord blood, and the majority of people’s urine. Higher levels are linked to more severe allergies.

• It may interfere with the body’s hormonal and immune systems. Exposure allows bacteria to develop resistance, including potential antibiotic resistance.

• When combined with chlorinated tap water, triclosan produces the carcinogen chloroform. Minnesota has banned it from 2017 due to these risks.

• Proper handwashing is still important for hygiene, but overuse of antibacterial products like triclosan is unnecessary and poses health and environmental threats. Regular soap is generally sufficient.

• Traditionally, human digestion and nutrition was seen as occurring only in the small intestine, where enzymes break down food into smaller molecules that can be absorbed.

• Recently, scientists realized the role of gut microbiota is crucial to fully understand nutrition. Microbes in the large intestine ferment fibers and produce molecules like short-chain fatty acids that impact host metabolism.

• Anthropologist Rachel Carmody realized her previous research on how cooking affects nutrition was incomplete without considering gut microbes. The interactions between host, diet, and microbes are key.

• Without soap or deodorant, many traditional tribespeople have no body odor due to helpful ammonia-oxidizing bacteria (AOBs) on their skin that convert sweat into odorless compounds.

• Modern hygiene habits disrupt the skin microbiome, reducing AOBs and allowing other bacteria to produce smelly metabolites from sweat.

• The company AOBiome proposes spraying a microbial product containing AOBs as an alternative to soap to maintain these bacteria and a natural smell. Some staff follow this approach with success.

• Our perspective on nutrition and hygiene needs to consider the roles of microbes rather than seeing the human body in isolation from its microbial communities.

• The large intestine was previously thought to simply absorb water and gather waste for excretion. However, its importance is being recognized.

• The large intestine is home to trillions of microbes that play a key role in nutrient absorption and vitamin synthesis. Without these microbes, our health and nutrition would suffer.

• Some animals like blood-feeding leeches and bats rely almost entirely on gut microbes to break down blood and extract nutrients, as blood alone does not provide a balanced nutritional profile.

• The giant panda is an example of an animal whose simple digestive system is reliant on gut microbes to break down the bamboo it eats and extract sufficient nutrients.

• Humans also rely on gut microbes in the large intestine to break down fibers and compounds from foods that our own enzymes cannot digest. The microbes produce molecules that are absorbed to provide nutrients.

• Changes in the modern diet including processed foods, more packaging, fewer home-cooked meals, and agriculture practices are impacting gut microbes and human health in complex ways related to diseases like obesity, diabetes and more.

• Comparing diets of traditional populations like rural African villages to Western diets can provide insights into evolutionary human diets and gut microbiome composition.

• The Italian children ate a typical modern Western diet high in fat, sugar, meat, dairy and processed foods. The Burkina Fasan children ate a traditional African rural diet based on grains, vegetables and occasional eggs/milk/meat.

• Their gut microbiomes differed greatly, with the Italian children dominanted by Firmicutes bacteria and the African children by Bacteroidetes bacteria like Prevotella and Xylanibacter.

• The key difference was the amount of fat and sugar in their diets. A Western high fat/sugar diet can quickly cause weight gain and microbiome changes in rodents.

• However, studies show that while fat and sugar consumption has risen globally, it has actually declined in some countries like the UK, yet obesity rates continue to rise there. Simply blaming fat or carbs is an oversimplification - the relationship between diet, microbiome and weight is highly complex.

• Surveys show that average daily calorie intake in the US peaked at 2,660 calories per person in the 1950s but dropped to 1,750 calories by 2000, even as obesity rates increased. USDA data also shows calories falling from 1,854 to 1,785 between 1977-1987 while fat intake declined slightly.

• Simply looking at calories in vs out or increases in fat/sugar consumption doesn’t fully explain rising obesity levels. Changes in other nutrients impact consumption of fat/sugar if overall calories stay the same.

• Children in Burkina Faso consume similar amounts of fat as Italian children but much more fiber - around 6.5% of their diet vs less than 2% for Italian children.

• Developed countries have seen dramatic declines in fiber intake from foods like vegetables, grains, beans and potatoes over recent decades.

• Low-fiber diets favor gut bacteria like Firmicutes associated with obesity over bacteria that break down plant fibers. Experimental diets show gut bacteria composition changes rapidly based on animal vs plant food consumption.

• Fiber intake may play a major role in obesity by impacting gut bacteria composition and metabolic effects rather than direct calorie or fat intake alone. Boosting populations of “good” gut bacteria like Akkermansia muciniphila through fiber helps prevent weight gain.

• The study examined the effects of adding various types of fiber to the diets of mice, including oligofructose and arabinoxylan (a fiber found in whole grains).

• Mice given fiber supplements had higher levels of beneficial gut bacteria like bifidobacteria and Akkermansia. Akkermansia levels increased 80 times with oligofructose.

• Fiber slowed weight gain in genetically obese mice and induced weight loss in mice on high-fat diets. It restored gut bacteria levels, lowered cholesterol, and reduced weight gain speed compared to no fiber.

• Short-chain fatty acids (SCFAs) produced by gut bacteria breaking down fiber are important. They activate GPR43 receptors on immune and fat cells, reducing inflammation and causing fat cells to divide instead of enlarge.

• Butyrate helps plug leaks in the gut barrier by influencing gene expression of tight junction proteins. A high-fiber diet feeds gut bacteria to produce butyrate.

• Fiber intake is linked to lower BMI and weight loss/maintenance in various human studies, even when fat intake is high. Higher fiber intake results in more weight loss compared to low-fiber diets.

• Cooking food made nutrients more available to both humans and our gut microbiota, allowing humans to develop bigger bodies and brains. Cooking destroyed anti-microbial compounds in plants, benefiting the microbiota.

• A strict raw food diet makes it difficult to maintain a healthy weight long-term due to lower calorie availability. Cooking is an adaptation, not just a cultural preference.

• Rates of gluten and lactose intolerance have risen dramatically in recent decades despite our evolutionary history of consuming these foods. This is likely due to changes in modern lifestyle damaging gut microbiomes.

• Our ancestors evolved lactase persistence after adopting dairy herding, showing tolerance helped survival. Intolerances today stem from impaired microbiomes, not inherently problematic foods.

• Restoring microbial balance through a whole foods, plant-rich diet in moderation may help manage intolerances, rather than entirely avoiding foods like gluten and lactose. Maintaining this relationship is important given our long history of consuming these foods.

• While many factors influence human diets and health, individuals ultimately bear responsibility for their own dietary choices and those of their children.

• Your gut microbiome plays an important role in your health and is influenced by what you and your family eat. When choosing meals, it’s worth considering the needs of your gut microbes as well.

• Many species ensure their offspring receive beneficial gut microbes, which help them digest plant materials like eucalyptus leaves in the case of koalas. For humans, vaginal birth transmits microbes from mother to child.

• In the first few hours after birth, as babies pass through the birth canal and interact with their mother, they acquire microbes like Lactobacillus that colonize their gut and defend against pathogens. Receiving these microbes provides infants with an advantageous start.

• Pregnancy shifts the diversity of microbes in a woman’s vagina in a way that facilitates seeding the baby’s gut with microbes like Lactobacillus that aid in milk digestion, as well as some gut microbes. This early colonization is important for establishing the infant’s lifelong microbiome.

• Microbial succession occurs naturally in the gut as initial colonies of bacteria establish and provide resources for more complex communities to develop over time.

• Babies born vaginally acquire beneficial vaginal microbes that colonize their gut and skin, influencing immune system development.

• C-section rates have risen dramatically worldwide in recent decades, with some hospitals now performing over 95% of births via C-section.

• Higher C-section rates are driven both by elective pre-labor C-sections as well as those performed during difficult labors for perceived risk management.

• C-sections carry greater risks to both mother and baby compared to vaginal births, including infections, hemorrhaging, and problems from abdominal surgery.

• C-section babies miss out on acquiring maternal vaginal microbes and instead take on microbes from their environment.

• This is associated with increased risks of conditions like allergies, autism, obesity, and autoimmune diseases later in life.

• Rising C-section rates may contribute to the increased prevalence of “21st century illnesses” by disrupting the natural colonization of beneficial microbiota in babies.

• A C-section baby’s first gut microbiota comes from the skin microbes of the mother, father, and medical staff present in the sterile surgery room, rather than the vaginal microbes acquired during a natural birth.

• This results in C-section babies having gut microbiota that does not match their mother’s and lacks lactose-digesting bacteria normally acquired from the vagina.

• Concerned about the impact on his daughter’s gut microbiota from an emergency C-section birth, microbiome scientist Rob Knight transferred vaginal microbes from his wife to his newborn baby after the surgery.

• Knight and Maria Dominguez-Bello are running a clinical trial using this technique of swabbing a newborn with the mother’s vaginal microbes after a C-section to see if it can ameliorate some short and long-term effects of C-sections on the baby’s gut microbiota.

• Preliminary results show babies swabbed in this way had gut microbiota more similar to vaginally-born babies compared to unswabbed C-section babies.

• Questions remain about how other birth contexts like water births or home births impact the transfer of microbes and establishment of the infant gut microbiota.

• Medicalization of birth in Western countries makes the process more sterile than in other parts of the world, which could impact the gut microbiota.

• Breast milk contains substances called oligosaccharides that help establish a healthy baby gut microbiome. They deprive pathogens of attachment sites and promote growth of beneficial bacteria.

• The oligosaccharide and bacterial content of breast milk changes as the baby ages, becoming lower in quantity and adjusting species to suit the baby’s changing microbial needs.

• Marsupial milk also displays this tailored adjustment, showing it evolved to selectively nourish the offspring microbiome.

• Breastmilk contains live bacteria that travel from the mother’s gut to her mammary tissue via immune cells. This helps seed the baby’s gut with useful microbes.

• The milk microbiota differs depending on delivery method, with C-section babies receiving milk less optimized for their gut colonization outside the womb.

• Formula feeding lacks these tailored components and sees higher pathogen quantities and less diversity in infant gut microbiomes compared to breastfed babies. This can increase health risks like C. difficile infections.

• Up to one-fifth of babies who are formula-fed carry Clostridium difficile (C. diff), a harmful gut bacteria. The longer a baby’s hospital stay, the more likely they are to pick it up.

• In babies, higher diversity of gut microbes is actually linked to poorer health outcomes. Breastfeeding and breastmilk optimally cultivate a selective group of beneficial bacteria to protect babies from infection and prime the immune system.

• Formula-feeding increases babies’ risks of various infections, diseases, and health issues substantially compared to exclusively breastfed babies. This includes ear infections, gastrointestinal infections, SIDS, eczema, asthma, leukemia, diabetes, and obesity.

• The risks of formula-feeding accumulate over millions of babies each year. While individual risk may seem small, the overall public health impact is significant.

• Breastfeeding duration is inversely correlated with obesity risk, with each additional month of breastfeeding lowering risk. However, most Western babies do not meet breastfeeding recommendations.

• Presenting information about “breastfeeding benefits” versus “formula-feeding risks” can influence mothers’ feeding choices. More transparent information is needed to support informed decisions.

• The gut microbiota changes significantly over the first few years of life as infants are exposed to new foods, environments, and microbial communities. Major shifts occur between 9-18 months as solid foods are introduced.

• Between ages 1-3, the microbiota diversity and composition starts to resemble that of an adult. Early differences from breastfeeding versus formula feeding are replaced by new strains acquired from other people and places.

• As children age, their gut microbiota becomes more similar to their mother’s due to shared genetics, environment, and diet within the home. This provides benefits as the immune system is primed to recognize familiar microbiota.

• The gut microbiota continues to adapt throughout adulthood in response to changes in diet, lifestyle, hormones, and environment. It helps synthesize or break down nutrients as needed to support the body’s changing needs.

• Living with other people results in sharing of microbial communities, with families and couples sharing the most strains. However, unrelated housemates can still converge in their microbiota due to shared living spaces.

• During pregnancy, women experience profound shifts in gut microbiota composition resembling obesity-related changes. These may help the mother store nutrients and energy to support fetal growth.

• Peggy Kan Hai became infected with Clostridium difficile (C. diff) after undergoing foot surgery and being given antibiotics, which disrupted her gut microbiome.

• C. diff is a particularly harmful bacteria that can cause life-threatening infections. It forms spores that allow it to persist even when exposed to antibiotics and cleaning agents.

• Peggy tried multiple rounds of antibiotics to treat the C. diff infection but it did not clear up and her health deteriorated severely.

• This led Peggy and her husband to consider taking drastic action to restore the microbial balance in her gut and eliminate the C. diff.

• Historical figures like Elie Metchnikoff hypothesized that gut microbes played a role in aging and disease. The “autointoxication” theory held that gut bacteria produced toxins that caused various illnesses.

• Peggy’s case illustrates how disruption of the gut microbiome, such as from antibiotics, can allow harmful bacteria like C. diff to take hold and cause infection. Restoring a healthy microbiome was seen as a possible solution.

• In the early 20th century, Russian biologist Metchnikoff proposed the theory of autointoxication, which argued that harmful bacteria in the gut caused illnesses and aging. He believed consuming “good” bacteria like yogurt could counteract this.

• The theory lacked rigorous scientific evidence but gained popularity. It led to colon surgeries and treatments like colonic irrigation and consuming probiotic supplements.

• In the 1930s, the theory started to lose credibility as the scientific standards of the time improved. A doctor named Walter Alvarez helped discredit it by dismissing patients’ concerns as psychopathic.

• While the underlying ideas weren’t completely unfounded, the lack of tools and rigorous methods undermined the scientific validity of autointoxication. Probiotics fell out of favor in medicine.

• Interest revived in the early 2000s as research improved. Studies now show some probiotic strains can provide health benefits when consumed in high enough amounts. However, specific health claims require strong clinical evidence due to regulatory standards.

• The human gut microbiome is highly complex, with trillions of bacterial cells from thousands of species. Introducing probiotics faces challenges of competition and limited ability to influence such a diverse ecosystem. More research is still needed to understand probiotic effects.

• Probiotics are live bacteria taken as supplements, usually in pill, powder or liquid form, to supplement or replenish gut bacteria.

• They have been shown to reduce antibiotic-associated diarrhea by replenishing gut bacteria killed off by antibiotics. Around 30% of people typically get diarrhea from antibiotics, but probiotics can lower this to 17%.

• Probiotics also help reduce infections and the duration of diarrhea in babies and children.

• They may provide some benefits for conditions like IBS, allergies, and eczema by reducing inflammation, but are unlikely to fully cure complex autoimmune or mental health conditions once they are established.

• Prevention seems to be better than treatment - in mice studies, probiotics significantly reduced the development of type 1 diabetes when given early, but were less effective when started later.

• Probiotics likely work by altering the immune system and increasing regulatory T cells that reduce inflammation.

• The specific bacteria strains and number of live microorganisms (colony forming units or CFUs) in a probiotic product matter. However, details are often unclear.

• As a last resort for severe C. diff infection, fecal microbiota transplantation (FMT) involves transplanting stool from a healthy donor into the patient’s gut to replenish bacteria.

• For many animals like hamsters, birds, and rodents, eating their own feces (coprophagy) is essential for proper nutrition, as it allows them to extract more nutrients from partially digested food. Preventing rats from eating feces slows their growth.

• In other species like elephants and chimpanzees, coprophagy is sometimes observed but considered abnormal behavior. Jane Goodall observed chimps with diarrhea eating each other’s feces, possibly to restore gut microbes.

• Zoo animals often engage in coprophagy due to boredom and stereotypical behaviors seen in autistic humans. It may be an attempt to correct an unhealthy gut microbiome.

• Experiments show providing chimps with indigestible fibers reduces coprophagy, suggesting they ingest bacteria needed to digest their normal foods.

• Studies in germ-free mice demonstrate coprophagy effectively transfers gut microbes between individuals. Mice housed with lean twins gained less weight than those alone.

• For humans, faecal transplant is an alternative to coprophagy for acquiring beneficial microbes, though the idea and process are understandably disturbing and revolting on a primal level due to evolved disgust reactions. Historical accounts show feces transplantation has been used medicinally for centuries.

The passage discusses how fecal transplants, though effective, have faced resistance from doctors and regulators due to perceptions of being unproven or unhygienic. It describes specific cases where patients with refractory C. diff infections or IBS saw dramatic relief after receiving fecal transplants. It then explains how MIT students developed a non-profit stool bank called OpenBiome to serve as a safe source of screened donor stool, enabling more widespread use of the treatment. While primarily used for gut conditions, some anecdotal evidence suggests fecal transplants may help treat non-gastrointestinal diseases like multiple sclerosis as well. Overall the passage argues fecal transplants are a highly effective treatment that should be more widely accepted and available despite initial squeamishness about the procedure.

• Several patients with various autoimmune/inflammatory conditions (MS, rheumatoid arthritis, Parkinson’s, ITP) recovered after fecal transplants, but it’s unclear if the transplants caused the remission or if they were spontaneous.

• Autism patients have also received fecal transplants or microbe-containing drinks, with some showing improved vocabulary and reduced gastrointestinal symptoms. However, more evidence is still needed from clinical trials.

• A study transplanted fecal matter from lean donors into obese men. Remarkably, it improved their insulin sensitivity within 6 weeks, nearly matching the lean donors. This suggests gut microbes play a key role in metabolic health.

• Further trials are studying if lean fecal transplants can also cause weight loss in obese people. Probiotics alone may have limited effects, while prebiotics that feed beneficial gut bacteria could be more effective for metabolic conditions like diabetes. Ultimately, fecal transplants and probiotics aim to deliver healthy gut microbes, and may converge in the future.

• Researchers are developing capsules containing freeze-dried stool (fecal matter) from healthy donors as an alternative to fecal microbiota transplants (FMTs) delivered via colonoscope. This would avoid inconvenience, expense and indignity of colonoscopy-administered FMTs.

• Professor Thomas Borody in Australia has developed “Crapsules” containing donor stool that cured an Australian C. diff patient when taken orally.

• Dr. Emma Allen-Vercoe in Canada is developing a synthetic stool cocktail of 33 cultured bacterial strains from a supremely healthy longtime antibiotic-naive donor found in rural India. This “RePOOPulate” mixture cured two female C. diff patients.

• As FMTs become more common, consumers may demand donors matched for things like diet, health status, personality traits. Finding truly healthy donors in the West is difficult due to antibiotic overuse.

• Studies show rural non-Western peoples like Amazonians and Malawians have more diverse gut microbiomes than Americans, dominated by fiber-digesting Prevotella lacking in Western guts. Western diets are damaging our microbiomes.

• The study compared gut microbiome genes involved in synthesizing vitamins from a vitamin-poor diet between US and non-US populations.

• Contrary to expectations, the US microbiomes contained more genes for vitamin-synthesizing enzymes. They also had more genes for breaking down drugs, mercury, and fatty foods.

• This reflects differences between carnivorous and herbivorous diets. US microbes were more equipped to break down proteins, sugars, and substitutes, while non-US microbes broke down starches from plants.

• Microbial restoration is an uncertain medical field, but prevention of dysbiosis is better than cure. Loss of microbial diversity makes us less human. Societies living antibiotic-free helped reveal the “proper” human gut microbiome.

• People in developed nations now need to restore biodiversity for future generations’ health. The hygiene hypothesis overstates the protective role of infections - our ancient microbial “Old Friends” are what we truly lack. Rekindling these relationships can improve modern health issues.

In summary, the study found US gut microbiomes had adapted to break down common Western diet components like drugs and meat, while non-Western microbiomes specialized in plant-based starch digestion. Prevention through maintaining microbial diversity is emphasized over unhealthy lifestyles and antibiotic overuse that disrupt our microbial communities.

• The microbiota, or gut microbes, are now recognized as a hidden organ that plays an important role in human health and disease. Chronic illnesses today have challenged doctors seeking cures and drug companies.

• Common therapies now treat symptoms rather than cure underlying causes, which were previously unknown but are now linked to the microbiota. Changes to the microbiota from antibiotics, low-fiber diets, and infant microbiota development threaten human health.

• Society can help by reducing unnecessary antibiotic use through better diagnostics, targeted antibiotics, and microbiota-boosting probiotics. Farm antibiotic overuse also impacts humans.

• Individual changes include improving diets with more plants and fiber, which support the microbiota. Microbiota monitoring and manipulation may someday optimize drug responses and reduce side effects.

• In the developed world, diets tend to lack fiber and vegetables. Meals are often quick, processed options that are low in plant-based foods. Workplaces also lack facilities for cooking and eating wholesome meals.

• C-section births have become more common than vaginal births in many cities. However, relatively little research has looked at the health impacts of C-sections and formula feeding during otherwise normal pregnancy/birth.

• C-sections may not be as safe as previously thought, as they alter the microbial community a baby receives in ways that could impact their health long-term. This has essentially made the current generation of children experiments in determining the impacts of surgical versus natural birth.

• Similarly, formula feeding has experimented on past generations by substituting cow’s milk instead of mother’s breastmilk. While alternatives are needed for some, improved understanding of breastmilk can help all infants.

• Individual choices around diet, antibiotic use, birth method and infant feeding can be made more consciously by considering the latest scientific research on microbiota and human health. When possible, opting to let nature take its course is advised.

In summary, the developed world’s typical modern practices and conveniences may be lacking important microbial exposures through diet, birth and infant feeding choices. Individuals have the opportunity to make more informed choices that support long-term health.

• The passage discusses making conscious choices about birth and infant feeding to nurture a healthy microbiome. It suggests opting for vaginal birth if possible and considering microbiota-boosting techniques like vaginal swabbing for C-sections. It also emphasizes the importance of breastfeeding for providing beneficial microbes.

• The main message is that we can influence our microbiome through lifestyle choices like diet, use of antibiotics and antibacterial products, birth method, and infant feeding. These choices impact the development of a diverse microbial community, which is important for health.

• While genetics play a role, the microbiome represents an environmental factor that is partially inherited from parents and influenced by our actions. Knowledge of this relationship can guide parenting and lifestyle decisions.

• Embracing our microbial communities, which have co-evolved with us, is an important part of understanding ourselves as 100% human from a biological perspective. Our actions can positively or negatively impact the microbial communities that inhabit our bodies.

• The passage describes making dietary changes to support a healthy microbiome, including eating more yogurt, beans, mushrooms, brown rice, lentils, rye bread, and adding vegetables like peas and spinach. This increased daily fiber intake from around 15g to 60g.

• Analyzing a second microbiome sample after these changes, there was a large bloom in Akkermansia bacteria and increased levels of butyrate-producing Faecalibacterium and Bifidobacterium. The author felt improved health effects from these changes.

• Thinking about having children, the author wants to pass on a healthy microbiome and plans a natural birth and breastfeeding according to WHO guidelines to transfer critical microbes to the baby.

• The author acknowledges antibiotics saved their life but also disrupted their microbiome. Going forward, they will only take antibiotics if really needed and use probiotics to reduce side effects. They want to prioritize their microbiome health.

So in summary, the passage describes dietary and lifestyle changes the author has made to support a diverse, healthy microbiome, analyze its changes, and how this influences their perspectives and future plans around childbirth and antibiotic use.

• OpenBiome processes donated stool samples to send for fecal microbiota transplantation (FMT) to help treat C. difficile infections in hospitals across the US.

• Volunteers wish to donate stool are screened for health issues. Only a small portion are eligible to have their stool processed.

• Donors’ stool is processed into a fecal microbiota preparation.

• Donors do not directly earn money, but OpenBiome likely relies on donations and stool donations to fund their operations processing and sending stool samples to help patients.

Here is a summary of the key points from the papers on human behavior and the gut microbiome:

• Several studies found associations between gut microbiota and behaviors or neurological/psychiatric conditions in humans like autism, depression, OCD, and schizophrenia. Alterations in the gut microbiome may influence neurotransmitter production or immune system signaling to the brain.

• Toxoplasma gondii, a common parasite, has been linked to behaviors like risk-taking and schizophrenia when it infects the gut. Gut bacteria can also influence infection susceptibility to T. gondii.

• The gut microbiome interacts with the brain through multiple pathways like the microbiota-gut-brain axis, producing neuroactive compounds, affecting serotonin and GABA levels, and stimulating immune responses that influence brain development and function.

• Imbalances in the gut microbiome (dysbiosis) have been implicated in mental health conditions involving inflammation like depression. Antibiotics that disrupt the normal microbiota during critical windows may also impact neurodevelopment and mental health long-term.

• Studies in animal models demonstrate that transplanting gut microbiota can transmit behaviors, stress responses, and neurological effects between hosts by influencing brain chemistry and immune signaling pathways between the gut and brain.

So in summary, emerging evidence suggests the gut microbiome plays a role in human behaviors, potentially through microbiota interactions with the immune system, production of neuroactive compounds, and signaling pathways like the gut-brain axis. Dysbiosis and disruptions to the normal microbiota are implicated in some mental health conditions.

Here is a summary of the key points from the provided papers:

• Paper 1 found that dietary arabinoxylan fiber was related to increases in the gut bacteria Bifidobacterium, Roseburia, and Bacteroides/Prevotella in diet-induced obese mice. Arabinoxylan consumption led to improvements in glucose tolerance and reductions in fat mass.

• Papers 2, 10, 11 discuss the role of the gut microbiota in diet-induced obesity and metabolic syndrome. Transferring gut microbes from lean donors to recipients with metabolic syndrome improved insulin sensitivity.

• Papers 3, 13 look at the role of bacteria and microbial-produced compounds like short-chain fatty acids in metabolic and inflammatory pathways related to obesity.

• Papers 4, 14-16 discuss dietary fiber and its role in body weight regulation and obesity risk. Higher fiber intake through grains and plant foods is associated with lower body weight and obesity risk.

• Papers 7, 9, 12 assessed delivery mode and infant feeding impacts on gut microbiota development in infants and later health outcomes like obesity and immune function. C-section delivery and formula feeding alter microbiota acquisition.

The papers overall assessed the role of gut bacteria in obesity development and potential prebiotic and probiotic strategies for modulating the microbiota and metabolic outcomes. Delivery mode, diet, and microbe transplantation were discussed as ways to influence the microbiota-host metabolism relationship.

Here is a summary of the key points from the pages referenced:

• Pictures show recruitment ads for stool donors for fecal microbiota transplants, and the processing and storage of donated stool samples by OpenBiome.

• A photo depicts Mary Njenga processing donated stool samples at OpenBiome.

• Pictures show the Kudzu bug, Peggy Kan Hai surfing, and hatching Kudzu bugs.

• A diagram depicts the Bobtail squid and its relationship with bioluminescent bacteria.

• The publisher’s note states they have made efforts to trace copyright holders of images but will rectify any omissions.

• The acknowledgements section thanks many scientists who contributed to the author’s research, as well as editors, agents, friends and family for their support in writing the book.

• Antibiotics have been used since the mid-20th century and have both decreased infectious diseases but also disrupted the natural gut microbiota. Prolonged antibiotic use can lead to conditions like C. difficile infections.

• DNA sequencing has provided insights into the microbial diversity present in and on the human body, including hundreds of bacterial species in the gut.

• The gut microbiota plays an important role in energy extraction from food, production of vitamins, training of the immune system, and impacting brain development and behavior. Dysbiosis of the microbiota has been linked to various diseases.

• Birth mode influences the transfer of microbes from mother to infant, with vaginal births providing more diverse microbiota than C-sections. Breastfeeding also transfers bacteria that colonize the infant gut.

• Probiotics like certain Bifidobacterium and Lactobacillus species can have health benefits when consumed. Prebiotics like fiber feed beneficial bacteria. Faecal microbiota transplants involve transferring stool from a healthy donor and have been used to treat recurrent C. difficile infections.

• Conditions linked to dysbiosis include obesity, diabetes, inflammatory bowel diseases, neurological/psychiatric conditions, and allergies/autoimmune disease. Diet, antibiotic use, and clean living also impact the microbiota composition.

• Maintaining a diverse gut microbiota through factors like diet, breastfeeding, limited antibiotic use and exposure to other microbes may help prevent some modern diseases and support overall health. The human microbiota plays a significant role in physiology.

Here is a summary of the key points from the specified sections:

io 136–7, 139–40, 200

• Discusses genes that influence susceptibility to cholera infection and progression to severe disease. Certain gene variants allow cholera to produce more toxin.
• Discusses genetics of coeliac disease, with genome-wide association studies identifying over 40 risk loci. HLA-DQ genes have the largest effect.

fat cells: appetite control 72, 73

• Fat cells secrete hormones like leptin that signal satiety to the brain and help regulate appetite. Less leptin in obese individuals results in feelings of hunger.

fibre and 196

• Fibre, particularly soluble fibre like psyllium, can promote the growth of gut bacteria that produce short-chain fatty acids like butyrate which support colonic health and may reduce inflammation.

lipopolysaccharide and 141

• Lipopolysaccharide (LPS) is a component of Gram-negative bacterial cell walls that is pro-inflammatory and linked to metabolic endotoxemia/insulin resistance in obesity and other metabolic conditions. Higher LPS circulating in blood may be due to a “leakier” gut.

in obese people 78–9, 141

• Obese individuals have differences in their gut microbiota composition compared to lean individuals. Higher levels of LPS and inflammation are seen.

in pregnancy 230

• The gut microbiota changes over pregnancy, favouring microbes related to infant nutrition. This supports the transfer of microbes from mother to baby during and after birth.

storage of fat 72

• Fat cells take up and store fatty acids and triglycerides as a way to regulate lipid levels in the circulation. This stored fat provides energy when needed.

• Measles outbreaks occurred in years 27, 28, 31, 38, 119, 165, 266. Meat consumption decreased in the 1970s and increased in fiber intake.

• Medical Hypotheses is a journal mentioned. Memory formation and memory B cells are discussed in relation to the microbiome.

• Meningitis, menstrual cycles, and various mental health conditions are discussed in relation to the gut microbiota and immune system. Gastrointestinal symptoms are also mentioned.

• Mercury and metabolic syndrome are discussed. The metabolism and metabolites are influenced by the microbiota.

• Elie Metchnikoff proposed probiotics in his book The Prolongation of Life in the early 1900s. MRSA, methicillin, and metronidazole are antibiotics mentioned.

• Memory formation and the microbiome are discussed. Memory B cells are immune cells that remember pathogens.

• Various conditions like C. difficile infection, mental health issues, streptococcus infections, and encephalitis lethargica are mentioned in relation to the gut microbiota and immune system.

Here is a brief summary of the key points from the passage:

• The human gut microbiome plays an important role in health and disease. It influences functions like digestion, immune system, and metabolism.

• Antibiotics have impacted the gut microbiome and contributed to rise of diseases like obesity, allergies, autoimmune diseases in developed nations. Overuse of antibiotics in agriculture is also a concern.

• C-sections, lack of breastfeeding, hygiene practices have reduced transmission of beneficial microbes from mothers to babies. This can affect microbiome development and long term health.

• Probiotics, prebiotics, dietary fibers are being studied for their ability to modulate the gut microbiome and treat certain diseases. Fecal transplants have shown promise in treating conditions like C. difficile infection.

• Imbalances in the gut microbiome (dysbiosis) have been linked to various modern diseases. Factors like Western diet, antibiotics, sedentary lifestyle can disrupt the microbiome.

• Indigenous communities have provided insights on how traditional diets and lifestyles supported a healthy gut microbiome and low rates of Western diseases.