Untitled Flashcards Set

During the COVID lockdown, parents have chosen to not have their children vaccinated. This is a huge social issue. This affects something called herd immunity. As a group, to not suffer from an infectious disease which you can be vacicnated against, there needs to be a certain threshold of number of people who need to be vaccinated against it. 

This is why COVID had the impact it did, we had no pre-existing immunity against it. 

Case study: Measles

This disease has been a part of the human civilisation since recorded history is available. The vaccine was developed in 1963, which led to a plummet in cases. Before this, nearly all children were infected by it, many died, many got encephalitis and so on. 

The vaccine was so effective, it prevented children from ever getting infected by it. Only recently, some parents are choosing to not vaccinate. 

Measles is highly contagious(high R₀), one person can spread it to 12-18 people. It is also a deadly disease. 

Recent times have debated the impact of this on their personal bodily autonomy. Is the measles vaccination a personal choice or a social responsibility? 

WHO declared that measles was eradicated, due to vaccination levels being so high. 

Herd immunity percentage is different for each disease. 

Vaccine hesitancy

Delay in acceptance or refusal of vaccines despite availbility of vaccination-services. Different from anti-vaxxers. 

Parents under-immunize children. This can be due to lack of confidence, complacency, lack of convenience. 

Vaccines were thought to be unsafe due to a perceived link between vaccination and autism. This was debunked due to fraud and irreproducibility, finally retracted. This did the worst for vaccine hesitancy. 

Safety concerns surrounding vaccine hesitancy

• Dont want to put a live virus: vaccines are small components of the virus, such as proteins rather than entire virus

• Dont want chemicals in your body; adjuvants are tested for safety, effectiveness in clinical trials before they are licensed for use in the US. what else are you willing to put into your body? Junk food, tobacco smoke, alcohol, then consider the power of vaccination to save lives. 

Microbiome gut-brain access

Microbiome influences your health in so many different ways. One of the ways is the central nervous system. 

The microbes in your gut speak directly to your brain through chemical signals, aka metabolites that interact with epithelial cells which trigger brain systems. The gut is constantly telling the brain what it needs to survive. 

All components of the system cross-directionally communicate, including the immune system, vagus nerve enteric nervous system, neuroendocrine system and circulatory system. A dysbiotic gut can result in altered social behaviour, including ASD, anxiety and depression like bejavipir, physical performance and motivation. 

The nervous system is the brain, spinal cord. These make up the central nervous system. The peripheral nervous system consists of somatic and autonomic nervous system, which is further divided into sympathetic and parasympathetic nervous systems. The spinal cord connects the brain and the peripheral nervous system. 

The whole system is made up of billions of cells that work to keep our body in homeostasis. When there is dysbiosis, there are issues with the upkeep of homeostasis. 

The CNS and PNS interactions

Eye take sensory information to the brain through a sensory neuron, where it is turned into a nerve impulse and then interpreted by the CNS through the process of integration. CNS then directs response to the stimulus. 

Enteric nervous system

Involves all of the nerves that regulate the breakdown of food. It has almost as many neurons as the brain that are embedded in the international epithelial cells. They detect the condition of the gut, integrate that information and provide outputs that control the gut’s actions. 

This is also called the second brain, as much of its function are doen independent of the brain. Communication and integration through the vagus nerve. Mostly chemically mediated.

Neuroendocrine system

Stress response system, with hypothalamus that releases corticiotropin releasing hormone which stimulates and triggers pituitary gland which produces ACTH.  

ACTH travels through the circulatory system to the adrenal glands and stimulates them to produce cortisol. This has multiple effects, including increasing glucose production, suppressing immune responses and diegstion. 

Blood-brain barrier

It is the intersection between the CNS and the circulatory system. It roadblocks microorganisms that might circulate in the blood. 

Microglia are the primary immune system of the CNS. This is developed during fetal development, many aspects of the neural system are directed to develop, control BBB, regulate immune function. 

Communication between gut microbiota and the brain

The routes of communication involve the ANS, ENS and vagus nerve, neuroendocrine system, HPA axis, immune system and metabolic pathways. 

SCFAs help trigger production of regulatory T cells. Dysbiosis leads to production of inflamed T cells. The gut microbiome has evolved with the nervous system to finetune responses to certain foods, what foods you chose to eat, how they taste, when you choose to eat etc. This means you can take direct control of your health by feeding your gut microbiome better. 

Microbiota gut brain communication

Cells in the gut influence directly through vagus nerve to the brain. The SCFAs speak and block things from entering your circulatory system through barrier integrity signaling. There is immune signaling, neurotransmetiters such as leptin and serotonin and vagus nerve activation.

Cells in the brain affect the gut by neurotransmitter communication, control of peristalsis, fight or flight stress responses through cortisol and secretion of mucus. 

Lactobacillus reuteri under good conditions triggers production of increased levels of oxytocin, regulating neuronal plasticity, increasing social behaviour. Microbes can trigger the brain to cause different behaviours, such as social behaviour through gut production of oxytocin. 

Lactobacillus rhamnosus helps produce GABA, which produces a calming effect. Ot ios a neurotransmitter that slows down brain activity by blocking signals. It reduces stress responsiveness. 

Bifidobacterium longum produces BDNF which reduces anxiety like behaviour and depressive behaviour. Reduces the excitability of the ENS neurons. 

Bacteroides fragilis results in a decrease in 4-EPS, which reduces anxiety and repetitive behaviour and increases communication. 

SCFA producing bacteria reduce stress responsiveness and anxiety and depressive like behaviour. 

This has therapeutic implications for treatment of mental health disorders. So maybe we should look into how food can treat depression and anxiety beforte taking antidepressant medications. 

Healthy gut microbiomes are fueled by high fibre diets which leads to production of SCFAs, rich mucus layer  and increased resistance to perturbations. 

Dysbiotic guts result in reduced SCFA production, fibre degrading species and increased mucin degrading species caused by low fiber diets. These result in glial activation and inflammation. 

Role of maternal gut microbiome in delta development

Involved in 

• neurogenesis- generation of new neurons- triggered by metabolites produced in the mother’s gut

• BBB creation and maintenance

• nerve axon myelination- allows a nervous impulse to be transmitted rapidly. Without this, there is an impact on how nerve cells move throughout the body. Disruption in this process can lead to long-lasting negative effects on CNS. 

• microglia maturation- immune system in the brain, recognise problems and destroy pre-cancer cells

• development and regulation of HPA axis

Dysbiotic maternal microbiome can have lasting impacts and is associated with various neurological disorders in the offspring. Germ free mice show that the neural development is not robust. The mice with abnormal axons have decreased startle response.

Endocrine route- slow, immune route- medium, neuronal- fast

GABA plays a key role in anxiety and depression disorders in mammals. Gut microbes produce GABA modulating rhe gut-brain axis response. 

Tryptophan 

Characteristic essential amino acid, precursor to serotonin. Gut microbes convert tryptophan to serotonin. Plays a key role in mood, sleep, digestion, nausea, wound healing, bone health and more.

Major Depressive Disorder

A leading cause of disability, morbidity and mortality worldwide. 

1 in 5 suffers from it during their lifespan. 

The brain is connected to the gut in so many ways, chemical, electrical, hormonal and so on. There is constant feedback and communication and when that breaks down, bad things happen. One example is MDD. 

Symptoms include

• Chronic emptiness

• Hopelessness

• Fatigue

• Unyielding sadness

• Restlessness

• No interest in hobbies

This is a global epidemic, partly triggered by COVID. In the past, it was considered to be a result of chronic stress and genetic predisposition. Treatment included long term psychotherapy and medication, more recently. 

Recently, we don’t believe it is only connected to brain dysfunction alone, it is also considered to be a result of chronic stress, antibiotic, poor diet, unhealthy lifestyle and general microbiota-gut-brain axis dysfunction. 

The biological cause of it is thought to be 

• Unbalanced neurotransmitters

• Impaired neurogenesis

• Decline in neuroplasticity

• Abnormal neuronal circuitry

Microbiome in the contact of depression

Depression alters brain activity in terms of executive function, reward, threat perception. The gut microbiome influences inflammation in the brain through tryptophan signaling which is impacting whether the BBB is working and if things are getting through the right amount and if the microglia are doing what they should be. 

It also affects the HPA activity and adrenal output. 

This is a novel understanding of the connection between gut microbiome and brain dysfunction resulting in depression.

Specific bacterial species and depression

• More eggerthella = higher levels of depression

• Eubacterium ventriosum is lower in the depressed individual. Has also been linked to obesity and traumatic brain injury. 

Men with depression have mycobacterium neoaurum in their guts. 

Noticed correlation betwene proline levels and severe depression. Less proline, less depression, more bidifidobacteria and lactobacillus. 

Depressed individuals have higher enterobacter. 

Treating depression with diet

Influence your gut microbiota by changing your diet and feeding the good guys with high fibre. Changing levels of stress and lifestyles can also improve gut microbiome and downstream impacts on depression symptoms. 

Microbiome and autism

ASD- refers to a broad range of conditions characterised by challenges with social skills, repetitive behaviour, speech and nonverbal communication. 

Affects 1 in 36 children in the US. There is likely gut microbiome dysbiosis, likely during fetal development. 

There is a link between infection during pregnancy and the chanhe of a child being diagnosed with autism. 

Without dampened immune response, there is a storm of cytokines which respond to the infection and th eepthelial cells are triggered by the immune system. The response gets passed to the baby, along with immune responses and metabolites have an impact on the cognition of the babies. 

Treating autism with probiotics

• Coprophagy- when mice eat each others feces and share their gut microbes

• L. reuteri- mice with ASD-like symptoms lack lactobacillus reuteri. When introduced into the mouse, some of the ASD-like behavipurs disappeared. We don’t know what causes this yet, and why only some strains of L. reuteri can reverse the ASD-like symptoms.

Gut microbiome and disease

Dysbiotic microbiomes have a lot of microbes that aren’t normally there. The good guys are low in number and the bad guys are higher in number. The body goes out of homeostasis and there are many cascading consequences on the body. 

Gut microbiome dysbiosis

• Loss of microbial diversity

• Overgrowth of harmful bacteria

• Reduction of beneficial bacteria (lactobacillus and bifidobacteria)

Nature abhors a vaccum. So when the normal residents are not prevalent, new microbes come in and start sucking up the metabolites from digestion. The toxins that these mcirobes produce attract more bad microbes and create other issues directly on the body. 

6 signs of dysbiosis

• Bad breath- bad bacteria are producing toxic gases that change the way your breath smells. 

• Excessive belching- not just from eating too fast and too much. 

• Fatigue- feeling chronic fatigue

• Skin conditions- abnormal responses to lotion, higher number of flare-ups, more frequent, hives from consuming certain foods

• Chronic constipation

• Healthy eating causes more digestive symptoms- asking the gut to eat what it is unable to eat, might make you feel worse when you do eat healthy

The gut has evolved for 900,000 years consuming fruit and grain. Recent developments have led to normalised consumption of things like hamburgers. The gut can’t adapt to that quick enough, leading to dysbiosis. 

Causes of dysbiosis

• Antibiotics and other antimicrobial agents

• Other drugs and medications

• Smoking and alcohol use

• Environmental toxins

• Physical and psychological stress

• Chronic inflammation

• Chronic diseases

• Food choices

What does dysbiosis cause

Gut microbiome and skin microbiome impact the health of the skin. Outcomes from gut dysbiosis include acne, psoriasis, skin cancer. 

Atheroscelrosis, thrombosis, heart failure can also be a result of gut dysbiosis. 

Gut - brain axis dysbiosis can result in psychiatric disorders, autism, neurodegenerative disorders

gut - lung axis dysbiosis can result in pneumonia and other respiratory infections, lung cancer, asthma, obstructive pulmonary diseases

Also has impacts on metabolis- obesity, type 2 diabetes, mitochondrial dysfunction and cancer

Dysbiosis and obesity

Healthy- low firmicutes, high bacteroidetes

Unhealthy- very high firmicutes, low bacteriodetes

This leads to 

• microbial fermentation of indigestible polysaccharides- For the same amount of input, the lean individual will make 250 cals while obese individuals will make 500cals. They extract the energy from food more, more of the food ingested will get converted to fat. 

• absorption of monosaccharides: faster conversion to adipose tissue

• production of SCFAs- wrong ratios, higher is not always better

Modified energy harvest from same amount of food. 

70% of americans are obese. We now understand that this has to do with microbiome, not just over-eating or sedentary lifestyle. 

Now we understand that genetics, high heritability and microbiome play key roles. 

Gut microbiome marker profiling

We see which bacteria are increased in dysbiotic obese and normal weight eubiotic healthy. 

Obese individuals have a completely different metabolic profile. They have lower variability in their gut microbiomes, healthy individuals have higher levels of microbiome diversity. Dissecting each of the species found in healthy vs obese, we can understand how each species contributes to obesity or health. 

Unhealthy profile is adapted to simple carbohydrates. Better able to extract energy from sugary foods. High levels of saturated fat, highly processed foods, diets consist of high fat, sugar, snacking, excessive alcohol. 

Healthy profile is adapted to something like a mediterranean diet. 

No FDA approved probiotics for weight loss, but increasing levels of probiotics in the diet can help improve paths to weight loss. 

Metabolic syndrome

Cluster of conditions that increase the risk of heart disease, stroke and type 2 diabetes. 

Criteria (3 of these): low levels of HDL cholesterol, elevated blood sugar levels, high blood pressure, excess weight in abdomen, hypertriglyceridemia. 

This is a result of guts being more efficient at energy harvest. Fecal microbiota transplants from obese mice to germ free mice, gain body fat with no increase in food consumption. This shows how important the gut is in the development of obesity. This shows that diet induced obesity can just be a result of gut microbiome dysbiosis. 

Depending on diversity of gut microbiome, the epithelial cells respond differently. This impacts the integrity of the tight junctions in the large intestine. 

In an obese individual, the increased levels of lipopolysaccharides reduce integrity of the tight junctions, leading to reduced energy harvest. 

There is a decrease in the levels of certain SCFAs and energy harvest.

The outcomes on the hosts metabolism are increased levels of fat deposition and increased insulin resistance. 

We are finding complex interactions between levels of different microbes. This is why therapeutics hasnt progressed in terms of this much. Each interaction plays a role in different aspect of digestion. 

Science is a process of one step at a time. We are at a point where we are confident that the gut microbiome contributes to obesity. We are now learning and working on how the separate elements interact together. 

There is a disconnect between the brain and the satiety signals from the stomach. There is a change in the biochemistry of ignoring satiety signals, which push us to ingest more and ingest the wrong foods. This leads to sugar consumption a very high levels. 

Akkermansia muciniphila- considered a keystone species in weight loss. on the path to becoming the next probiotic to improve weight loss. 

• Comprises 5% of the gut microbiome

• Feeds of mucin, stimulates more mucin production ensuring the right amount is always present

• Mucine fermentation produces SCFA propionate and acetate which are implicated in a well balanced microbiome and healthy host

• It produces protein Amuc 1100 which improves gut integrity by increasing expression of genes encoding claudin 3 and occludin. 

Allergic diseases and the gut microbiome

There is a food allergy epidemic, with food allergies among children increased 50% between 1997 and 2011. 

An epidemiological perspective shows that the genetic component only underlies some small part of why there is a rise in food allergies. The gut microbiome plays a role in why this epidemic has happened. 

An allergic reaction

• Sensitisation: initial exposure to an allergen, where a pollen grain (for ex.) enters the bloodstream with antigenic properties. This triggers B cells to differentiate into plasma cells and make IgE antibodies, which attach to mast cells. Upon first exposure, the body doesn’t react as dramatically. 

• Allergic reaction: second exposure to same allergen. Allergen binds to IgE antibodies on mast cells. This causes histamine release from the mast cell which triggers an allergic reaction. Histamine cells cause inflammation in different parts of the body depending on where it is released. 

This cascade of events is known as an allergic reaction and impacts your physiological response to a foreign body. 

IgE is created based on the foreign body particle it binds to. This creates allergen specificity. Extreme allergic reaction - anaphylactic shock. 

Immune response

Antigens present to antigen-presenting cells which triggers a response by naive T-cells. These differentiate into T helper cells 1 or 2. 

• T helper cells 1 respond to infections

• T helper cells 2 respond by signaling B cells which differentiate into plasma cells, which produce IgE antibodies

Th2 allergic cascade

Th2 cells were created to respond to parasitic worms, which we don’t really use anymore. 

This results in Th2 to respond to harmless antigens which results in allergic response. They secrete cytokines, such as interleukin 4, 4, and 13 which promote IgE production by B cells. IgE binds to mast cells which release histamine. 

Maternal factors impacting fetal immune cell development

Factors such as Western style diet, maternal immune activation, stress levels, drugs, maternal microbiome and bacterial metabolites all have an impact on fetal immune cell development. 

Mother’s microbiome and activated immune system from eating a bad diet, are making their way through the placenta and into the fetus and triggering immune responses and activation or inhibition of neurogenesis. 

Vaginal delivery is the best way for developing a strong microbiome. Neonatal immune system is very nascent. Baby is dependent on maternal immune system byproducts and metabolites like SCFA to build an immunity if met with dangerous infections. 

What mom eats is as important as anything else that mom does during those months of pregnancy. 

Mothers who have a low fiber diet result in lower levels of SCFA which leads to inhibited IgA and IgG in the fetus resulting in more asthmatic symptoms. 

Mothers with high fiber deits produce more acetate which triggers Treg (regulates inflammation) production which limites asthmatic symptoms. Lesser Treg=increased Th, which means more inflammation. 

For every unit increase in the odds-ratio, the odds of allergic diseases are decreased for asthma, eczema, food allergy, and hay fever. 

Babies without asthmatic symptoms show increased bacterial diversity and quantity. 

Factors impacting-

• Vaginal delivery +

• Home delivery +

• C-section -

• Antibiotics -

• Maternal high fibre diet +

• Daycare and exposure to older siblings  +

• Premature hospital dleivery -

• Household pets +

• Maternal farm exposure +

• Farm exposure +

Hygiene hypothesis

Study done on Amish children and Hutterites

Natural farming techniques vs mechanised crop production.

Children of Amish parents had 4 fold lower levels of allergic disease and asthma. 

Children from amish homes rarely experience allergic reactions. 

Atopic March

The atopic march refers to the natural history of allergic diseases as they develop over the course of ifnacy and childhood. It clasically begins with atopic dermatitis and progresses to IgE-mediated food allergy, asthma, and allergic rhinitis or seasonal allergies. 

It is proposed that allergic disease results from the failure of the gut microbiome to produce sufficent butyrate. Without butyrtae, naive T cells cannot differentiate into T regs, impairing the ability of the immune system to suppres excessive immune response to things that are not going to kill you. 

Hygiene hypothesis says we are too clean now and not exposing ourselves to bacteria enough.

Old friends hypothesis

Early on infections were able to persist as relatively harmless subclinical infections or carrier states. Fetus had exposure in utero and after birth. 

These pathogens had to be tolerated and played a role in the development and regulation of the immune system. 

With the onset of western lifestyle and medical practice, we deplete the old infections, causing immunoregulatory infections to increase and the immune system has become more dependent upon microbiotas and the natural environment. 

Microbes that never used to be harmful btu simply train the immune system are not wiped out and there is no exposure to them. 

Urbanisation has also led to a depletion of our microbiota and less exposure to microbes in the natural environment. 

This results in crowd infections, such as childhood viral respiratory infections which lack immunoregulatory roles. 

Biodiversity hypothesis

Contact with natural environments enriches the human microbiome, helps to promote immune balance and protects us from allergic disease. 

• Endorse health, not allergy

• Strengthen tolerance

• Adiot a new attitude to allergy, only avoid allergens if necessary

• Recognize and treat severe allergies early to prevent exacerbation

• Improve air quality and decrease smoking

Current practices have led to microbial deprivation, which results in disturbed immune response and microbial imbalance which leads to the high risk of inflammatory diseases. 

Finnish allergy program

Based on the biodiversity hypothesis, Finalnd soight to reduce allergic disease across the entire country through changes in perspective of what is good and what is bad for newborns. 

Found that with these changes, reduced allergy diet prevalence, occupational allergy, asthma medications and days spent in hospitals and lower asthma allergy costs. 

Physicians did not change how they treated patients, just taught them to change their outlook on allergens. Changed the way immune systems developed in children. Simple changes, low harm and widespread benefits. 

Antibiotics and allergic disease

Immature gut microbiome with antibiotics leads to an increased risk of obesity, asthma, immunosuppresive disease etc. 

If a pregnant woman or newborn is given antibiotics, it will have an influence on their later health. An immature gut microbiome with prescribed antiobiotics, leads to decreased activation of immune cells, reduced innate immunity and reduced adaptive immune responses caused by reduction in antibody production by plasma cells. With exposure to more allergens, more allergic reactions are caused by mast cell degranulation. 

Innate immunity is the immunity we are automatically born with, for example our skin and bacteria in our mouth. 

Adaptive immunity is the immunity we gain from birth until we gain a mature immune system. 

Newborns who receive antibiotics have reduced levels of bifidobacterium and increased levels of enterococcus. Within a month, these babies have elevated levels of inflammatory enterobactericeae. Children prescribe dantiobitics during their first eyar if life have a 200% increased risk of developing asthma and a 20% increase in risk for each additional antibiotic prescription. 

Asthma

One of the most common chronic airway diseases

Results in inflammation and swelling in air passages

Caused by genetics, immunological factors and microbiome

Likelihood of developing asthma and its severity is heaviyl influenced by early life exposure to microbes

What happens in an asthma attack

• Activation of eosinophils, which are whiteblood cells involved in inflmmatory response, leading to hypersecretion of mucus, enlargement of mucin-producing goblet cells and airway hypersensitivity to allergens. 

• The Th2 response is dominant in asthma, they release a variety of cytokines like IL4, IL5 and IL13. 

Airway microbiome

Comparing a healthy airway and asthmatic airway, there is a loss of diversity in the asthmatic, with increased homophilis, proteobacteria and others, and reduced keystone species. Caused by corticosteroid, microaspiration, smoking, age, BMI, nutrition and local condiitons. 

Dermatitis

Inflammatory skin condition that causes your skin to become dry, itchy and bumpy. Rashes develop, scaly regions and sometimes infections develop. This condition weakens the skin’s barrier function. 

Caused by deficient skin micrnbiome on that part of the skin, loose epithelial junctions. 

This is caused by reduced diversity of microbiome. There is dysfunction of the skin epithelial cells and alterations in immune responses.

Potential for roseomonas mucosa as a treatment. 

Now that we understand our dysbiotic microbiome can cause disease, what do we do now?

Studies have revealed the 1000 day window where a baby’s gut microbiome development can have significant positive effects on health. 

Immune system responds with too much sensitivity. 

Good news- we have the ability to control what we eat and how we can address the issue of our microbiome. 

Bad news- we aren’t at a point where we can say this will definitely solve the problem and cure allergic diseases.

• Address your lifestyle and diet: powerful approach to remediating a dysbiotic microbiome, can be done without a diagnosed dysbiotic microbiome. Eat fermented foods, get moderate exercise, expose yourself to microbial diversity, eat prebiotic fiber-rich foods, sleep well and target microbiome supporting nutrients. 

• Probiotic and prebiotic treatments- eat to feed your microbes; resistant starches and fibre rich foods, last resort- prebiotic supplements. Understand what foods are prebiotic. Short course fo probiotics might help, but this is conflicting. 

  • Prebiotic

  • Probiotic

  • Symbiotic - prebiotic food and probiotic strains that can improve gut health when they enter the digestive tract. They help produce butyrate, SCFA, which cause immune system to not release histamine. It reduces response to food allergies. 

• Bioengineered therapies for asthma- prevent formation of regulatory T cells which helps control immune responses. 

• Fecal microbiota transplants- microbiome based therapeutics, include the actual microbe. Symbiotic consortia- taking known groups of species and introducing it to the microbiome; engineered symbiotic bacteria- bacteria made to produce lots of SCFA, microbial metabolites- expensive. 

Our evolving microbiome

It's taken millions of years, since before we shared our last common ancestor, with natural selection, we have evolved the different microbiomes that exist within us and around us. 

Microbiomes are selected based on host physiology and genetics. Our gut microbiome co-evolves with us. They have descended from the ancestral microbiota that evolved in the common ancestor of humans and our close relatives, the great apes.

Great apes diverged 15 mya, they share not only a common ancestral primate and an ancestral microbiome. 

As the host evolved, so too did the microbiome. The primate host and their microbial symbionts share a similar evolutionary history.

The shared ancestry of the host and microbiome, shared branching patterns, which means that the microbiome evolved within the hosts. 

If we only partially shared ancestry of host and microbiome, it means their branching patterns are not fully shared which suggests that they did not grow and evolve within the host. 

Most phylogenetic trees show shared ancestry of host and microbes, all strains from one host are more closely related to strains of that same host. 

Some trees show transfer events, such as Gorillas gaining a species from Bonobo. 

There is such an intricate interaction between microbiomes and the different parts that make us up. 

We have had them in our bodies for so long that we should not be surprised at how they are dependent on us for being a good host entity. We are evolving much faster in the last 150-200 years that microbes have not caught up and result in them being in a state of flux and causing dysbiosis and problems within our bodies. 

In this shared history, we see 35 divergences since the divergences of the great apes. Nearly half of those changes occurred during the split between the human and the chimp. Bacteroides is fivefold more abundant in humans since it is associated with diets rich in fats and proteins. This suggests that the switch to the human lifestyle accompanied a huge shift in the microbiome. 

Based on diet, we have strengthened the bacteria that can digest fats vs bacteria that can digest others. Humans and chimps share 99% of the gene content, they are our closest living genetic relatives. 

Humans and chimps

They have very similar microbial compositions. Both dominated by firmicutes and bacteroides, around 60%. 

This is surprising given the dramatically different environments, social interactions and diets the two species have. 

Enterotypes are microbial communities that have adapted to a particular environment. This organisation is preceded by the divergence of chimps and humans. Humans and chimps share most of the same genera in their gut microbiomes but the precise species within those genres differ, likely due to selective pressures that differ between these hosts. 

PCA is a way to simplify and visualise complex data, the most important bit of this data that helps us separate these two organisms. 

Something about the way we host microbes is very similar to the way chimps host microbes. 

Microscopic views of samples of feces from 700 year old altrines show typical species found in human feces today. 

Corprolites and the ancient human gut mcirobiome

• More diversity

• Dietary adaptations from high fibre plant based diet

• Ancient bacteria that shift with lifestyle changes

• Presence of pathogens that suggest resilience to certain diseases

• Loss of function, loss of bacteria that digest complex fibers

• Antibiotic resistance genes- some resistance genes present. 

Ancient plaque microbiomes

Fossilised plaque contains DNA from the microbes that built it. 

Core oral microbiomes- shows deep evolutionary conservation of biofilm structure. There has been a conservation over evolutionary time of the microbiomes in our gut and teeth. 

Changes in the oral mcirobiomes may have helped fuel the icnreased brain size in humans. This elarged brain would consume 25% of our glucose each day, which needed a new supply of energy. This was brought about by a transition to starch rich foods that provided extra energy even before the agricultural revolution. These microbes helped digest the starch and release much more energy than before. 

Comparing the BaAka, Bantu and US Americans, we can see that lifestyles and diet matter a lot. The BaAka people live hutner-gatherer lifestyles, wild game meat, fruit and fish. The Bantu people run based on a market economy of growing tubers, raising goats for meat and use antibiotics. They are the in between for a Westernised population vs traditional hunter gatherer populations. 

Cellulose degrading bacteria of hominids across evolutionary time

They are rare in urbanised human populations, but prevalent in nonhuman primates, great apes, ancient human populations, hunter-gatherer communities and in rural populations.

Industrialisation began with humans building environments such as homes, offices, public buildings, cars, roads, public transport, drinking water, sewage treatment plants, swimming pools etc. 

The microbial communities associated with humans and their built environments. Which can be impacted by building design, function and individuals. 

Pets bring a higher number of helpful microbes into our environment. Moisture affects the microbes in our house. Plants, herbs, and flowers also bring helpful microbes. Distance from farm environments also affects our immunity signals. 

This microbiome of the built environment began when chimps started building nests in trees to sleep in. This expanded to caves and other structures. These were primitive built environments. There is a strong connection between nature and the built environment, with only 3.5% of them having chimp origins, the rest were soil microbes. 

If we look at microbes in the beds we sleep in today. Week 1 has 3 million distinct microbes and week 4 is 11 million. 35% comes from us, the rest comes from wherever the sheets have been. We leave a microbial trail everywhere we go. 

We first began to build our built environments 12,000 years ago. We started separated from the natural environment, semi-permanent shelters became the focal point for social interactions. 

The first true home was identified in Native Americans in the 1540s. Their homes had high levels of M. tuberculosis, which might have been due to less sunlight and low ventilation rates. 

Human population densities increased, with the emergence of cities, came overcrowding, poor sanitation and poor ventilation, less access to healthy food and healthcare facilities. This leads to increased disease. The first one documented was the Justinian plague in 541, caused by Yersinia pestis, vectored by fleas and carried by rats. 

Comparing primitive and advanced built environments, sampled the surfaces in each of these environments. Advanced BE have become increasingly closed to ventilation. When we do PCA of jungle, rural and city environments, we see tight clusters. In the jungle, we see high consistency across diversity, more representative of soil microbiome. In rural areas, we see samples from different locations have lower levels of diversity. More representative of the human microbiome. In the city area, we see very little diversity and microbes are almost exclusively representatives of the human microbiomes. 

By this, we are increasing the number of pathogens we have around us and less access to microbes that we co-evolved with for millenia. 

Humans spend 90% of their time indoors, shedding and respiring microbes. When new occupants enter, the microbes they release can colonize in a matter of hours. 

Microbiome of the built environment depends on building layout, design, airflow, ventilation and material used to build the environment. 

Sick building syndrome- many residents of the same complex have the same issues, might be related to the amount of time they spend indoors. 

Legionnaires disease- 1976 at the American Legion convention which killed around 10% of people. Pathogen legionella was found in cooling towers of hotels, circulated by AC. Also found in hot tubs and plumbing systems. Symptoms found in flu, can result in fatal pneumonia. 

Other building associated diseases include occupational asthma, allergies etc. 

Hospitals- special case of MoBE

Hospitals go to a much greater degree in terms of cleaning and disinfection. This is because microbes were traditionally thought to be bad for us- especially after the germ theory of disease. Microbes were labelled as bad and disease causing. Very few were considered helpful bacteria. Hospitals therefore eliminate bacteria. 

440,000 infections are caused by simply going into a hospital. This costs us nearly $10 billion. 

Patients in hospitals often have a suppressed immune system. This puts them at an increased risk of infection by bacteria that are resistant to antibiotics, some of which may come from sources in the hospital environment. They provide a reservoir of antibiotic resistance genes. 

Hospital microbiome project

Before opening, more soil based microbiome. After opening, more human based microbiome. On the patients first day, microbes move from surfaces to the patient and by the next day, the microbes moved in the other direction. 

NICUs

Kept as sterile as possible to prevent the spread of apthogens

Numerous pathogens are detected at higher levels in the nasal passges of babies after 13 days in the NICU compared to vaginal birth babies. Higher levels of antibiotic resistance genes were detected in NICU babies gut microbiomes. NICU babies only have transient immunity from their mom. 

Premature babies in the NICU eng up having a dysbiotic microbiome, antibiotics which results in less bacterial diversity, increased relative abundance of pathogenic bacteria in their, on their skin and and in their nose and decrease or absence of symbiotic bacteria such as bifidobacterium. 

This has led to the idea of off the wall approaches to infection control in hospitals

• Its costly and not very effective

• What if we just spray commensal and ogod bacteria and keep plants in the hallways and patient rooms.

• We can just exclude pathogens by filling their niches with commensals. 

Exposure to environmental microbes can reduce the levels of human pathogens in particular by increasing outside ventilation and access to sunlight. 

Florence Nightingale proclaimed the virtue of opening windows to increase rate of healing and decrease death rates. 

Designing future cities with MoBE in mind

• HVAC systems to limit viral spread

• Adding plants to roofs and public areas to increase MoBE diversity

• Public transport to limit pollution and share microbes passively. 
  

Ecosystem based approaches are going to have an impact on our microbiome but we don’t know to what extent this will work. They are proposed to address environmental, cultural and societal challenges while increasing microbial diversity in urban centers. 

The benefits are competitive exclusion of pathogens, exposure to beneficial microbes, immune protection and increased habitat biodiversity. We are creating vacuums in our microbiome, which is causing an increase in human related pathogens multiplying to make up our microbiome. If we fill up our microbiome with good bacteria, it can result in a cascade of positive things. This will increase the diversity in this gut habitat, reducing allergies, asthma, gut issues and obesity. 

Taking charge of your microbiome

How do we define a healthy microbiome?

A healthy ecosystem is one that hosts a high level of biological diversity such that it is resilient in the face of change and stressor and is able to return to a healthy state when perturbed. The number of connections in an ecosystem is a predictor of health. 

Gut microbiome health index

• Provides a summary statistic that may be useful to a physician in detecting dysbiosis

• Higher GMHI- higher species, richness and abundance is associated with health

• Blind test- 74% of the time correctly identified stool samples from either healthy or non-healthy individuals

• Biased sample of stool-white, westernized etc.

The best predictor of gut microbial diversity is eating 30 different plants in a week. This is based on studies that found that people who eat a wider variety of plant foods have healthier microbiomes. 

• Eat the rainbow

• Eat fermented foods

• Eat within a 10-12 hour sleep window

• Eat fewer ultra-processed foods