I Contain Multitudes: The Microbes Within Us and a Grander View of Life

Book: I Contain Multitudes: The Microbes Within Us and a Grander View of Life
Author: Ed Yong

(Listening in progress)

The people who thought to look

• I did not take much notes for this chapter, but the author describes the history really well. Worth a re-read (or re-listen).
• It is a bit crazy that multicellular organisms only evolved in October whereas a single cell organisms existed from March.
• “Animals might be evolution icing but bacteria is a cake” - a very nice metaphor!
• Function is more important for a microbiome constitutions than identity. Different bacteria can replace each other and provide the same function the same way you have different predators in different regions which provide the same function.
• Similar species of bacteria that convert CO2 and H2 into methane live in hot springs, swaps and also in our gut!

Body builders

• Microbes as body builders. Light emitting bacteria controlling squid development.
• Virtually no livable surface have bacteria. So bacteria are a good measure of habitability of a location on a surface. Sensing chemicals emitted by bacteria and using them to evaluate a surface seems like a good strategy. Without them, most sea organism with a motile phase won’t settle down until adulthood.
• Germ-free mice not just get infection, they are susceptible to auto-immune diseases showing that microbiome is necessary to train the immune system.
• Mice which shows symptoms of autism show a reduction in symptoms when their gut is enriched with the right bacteria. This shows that some symptoms of autism is linked to how the microbiome shapes behavior! (caveat: mouse with autism doesn’t necessarily translate to humans).
• Gut microbiome and behavior - how an enriched gut can remove symptoms of anxiety, stress etc.
• Symbiosis is conflict. Conflict that cannot be totally resolved but can be it managed and stabilization. Partnership requires rules and constraints to prevent cheaters.
• Repeat evolutionary occurance of bacteriosomes or bacteriosites in insects and arthropods - organs that enclose symbiotic bacteria that allows them to thrive without invading the body and activating the immune system. It also manages conflict.
• Mucus - the universal wall to manage conflict with symbionts. Bacteriophages - the soldiers that man these walls. Higher concentration of bacteriophages in mucus, maybe even selective preference of particular species to control bacteria population (might be just evolutionary).
• A consequence is that our symbiosis is not just with bacteria, but also bacteriophages to keep the bacteria in check.
• Maybe the first immune system was actually mucus + viruses. Mucus provides an environment that allows viruses to infect bacteria much more effectively.
• Human (mammalian) gut has two mucus layers - the dense mucus layer and the shallow/light mucus layer. The light mucus layer contain bacteria and bacteriophages, and is a thriving symbiosis oasis. The dense mucus layer is a demilitarized zone - the bacteria find it tougher to enter and the epithelial tissue spray antimicrobial peptides preventing entry. Immune cells sample this region and prepare antibodies for bacteria that come across the dense mucus (and wait readily behind the epithelium). One view is that this method allows the immune system to calibrate and manage conflict. Another is the symbionts use immune system to develop adaptations and weed out competitors.
• An interesting idea described in the book is that immune system developed to maintain and manage conflict between the organism and microbiome. And for mammals, with complex immune systems, the idea is that this evolved to manage a more complex and diverse microbiome.
• Immune system is suppressed in the first 6 months to help bacteria flourish and establish in the gut (and other places). It’s not that the immune system is immature (as commonly believed). Mother’s milk contains antibodies that help establish the right bacteria and suppress the others.
• Human milk contains 200 types of oligosaccharides (Human Milk Oligosaccharides) that cannot be digested by a baby! They might be food for the bacteria and not the baby, helping set the right cultures during the first 6 months (when the immune system is suppressed).
• HMOs help establish the right bacteria so that they can digest the oligosaccharides and provide chemicals which is important to develop the brain. The other perspective is that the oligosaccharides can block or attach to pathogens (even HIv) giving the baby sometime to develop immunity.
• Milk has something which allows gut viruses to bind to mucus 10 times better than normal.
• You can imagine a huge group of bacteria and bacterial phases forming a self sustained community on the mucous layer and slowly digest food coming in through the intestine.
• The crux is that food coming inside through the gut is full of bacteria so it is not possible to completely wipe them out. The priority then is to seed the gut with the right group of bacteria that would be beneficial for the host. This group of bacteria should protect the gut from harmful bacteria that can inflame/infect the gut, and as a bonus maybe help the host by providing nutrients in return for the safe haven. I like this perspective - when viewing the world as completely covered with bacteria and virus, this perspective makes complete sense.
• And from this perspective, dysbiosis is essentially symbiosis gone bad. Difference between symbiosis and desperiosis is basically the stable community of bacteria which resist changes. In symbiosis the stable community of bacterias good for the host and maintains itself stably so that bacteria that are harmful to the host do not take hold. In Dysbiosis, the opposite happens. The community of bacteria is not necessarily good for the host and often detrimental, but the community is stable and resists new bacterial species that are often beneficial to the host.
• The community of bacteria in the gut is influenced by the immune system and vice versa. The hygiene hypothesis shows how the exposure of different varieties of bacteria actually has an effect on the immune system - it trains the immune system to be it less jumpy (allergy) and more precise when targeting harmful bacteria.
• Saturated fats can help inflammatory bacteria thrive and prevent non-inflammatory beneficiary bacteria to take root. So can two major preservatives that are using things like ice cream.
• Fiber rich diet seems you have a beneficial effect - people from Uganda who eat seven times more dietary fiber have lower instances of diabetes, heart disease, colon cancer etc. It looks bacteria that can digest fiber produce non-inflammatory molecules called short chain fatty acids that basically clamp the immune system (over) response. In the absence of fiber these bacteria digest the mucous membrane, making it thinner, which in turn move bacteria closer to the immune system causing inflammation. It looks going to a low fiber diet and then moving back to a high fiber diet will not cause all the bacteria to come back.The transition is not completely reversible and something we just have to remember and deal with.
• Antibiotics alter the balance between symbiosis and dysbiosis, as they kill beneficial bacteria as well which in turn opens up the microbiome allowing for more harmful bacteria to come and settle.
• Chapter ends with a nice few paragraphs of what current microbiologists are doing. They are trying to ascertain causality by mixing bacteria, transplanting into germ free mice and see if they cause or rescue symptoms. Need to check this out in detail later.
• A lot of the ideas about the gut microbiome shaping the immune system is also talked about in Immune.

Long waltz

• The chapter starts with a description of different ways in which animals mothers end of their children with the right microbiome. He talks about a lot of creative ways in which insects and animals provide paste or fluid that the offspring eats or gets engulfed in when they are born. This provides the the right beneficial microbes which have slowly coadapted including more evolutionary adaptation and benefit for both parties.
• Given that there is specificity between both the host and the microbiome they host, that is certain microbes are preferred by the host and even modified evolutionarily to only survive in the hosts, it becomes hard to think of the microbiome and the host as separate entities.
• The author brings in the idea of the extended phenotype borrowed from Richard Dawkins book. The idea of the extended phenotype is that the gene does not just code for the animal but also all its behaviors. As a consequence the modification of the world as an effect of the behaviors falls under the phenotype of the gene. So the extended phenotype of humans for instance is all the modification of the world that is being done. This is an interesting idea not directly pertinent or linked to microbiome because in case of the extended phenotype the directionality is from gene to outside. In the case of the microbiome that is bidirectionality.
• Another idea call the holobiont. The idea here is that evolution acts on both the host and the bacteria together, both evolving traits that as a whole increases fitness of both. So the proponents of the holobiont idea argue that the unit of evolutionary action is not a gene but actually a combination of the host gene and the bacteria gene, what’s they call the hologenome. This is a very controversial idea and is fiercely argued in the field. The critics of this idea argue that evolution does not actually act on both the host and the bacterial gene together. The fact that symbiosis can go awry with symbiotic bacteria turning harmful is proof that evolution actually acts independently both on the host and the bacteria (basically dysbiosis is the counter point for this idea). This is a very valid argument and I agree that the holobiont theory seems too early and needs more rigorous thought and experiments.
• There’s some weird experiments which do give credibility to this idea. One experiment is where two groups of fruit flies were fed two different food sources for multiple generations. When these two groups of fruit flies were placed together, the fruit flies fed on one food source preferred to mate with flies the day at the same food source. This is very remnant of initial speciation indicating that the host plus the microbiome is a species here. Some experiments were done with wasps from different species which when made sterile hybrids. However, when fed with antibiotics these hybrids can mate suggesting that the speciation is it actually an effect of the microbiome similar to the fruit fly experiment. All these show that there’s some intermediate between evolutionary forces acting on individual genes and what is defined as a holobiont.
• What is clear is symbiosis affects by the host and the microbiome bidirectionally causing changes to both and sometime even speciation changes to both. This is cool!