1.3 A Dynamic System (1)

Viewing ourselves as an ecosystem like a city in river valley or a holobiont (a systems biology approach) makes it much easier to understand how humans and microbes have evolved together to perform functions the neither could do alone. However, this relationship goes far past these simple associations. Just as early man irrigated and domesticated Mesopotamia, changing it to a land that could support many humans living together, microbes actually aid in the development of our immune system and the our digestive system. In a lifelong process, microbes educate and develop our immune system so that it can better protect us from pathogenic invaders. Microbes instruct gut epithelial cells to form tight junctions, fortifying the barrier between our inside and the outside world that flows through the GI tract. Microbes help in the digestion of dietary fiber from plants that we could not process ourselves, thus extracting energy for both them and us. Many microbes can live without oxygen and can use food energy in this oxygen-free environment where our human cells cannot survive using a process called anaerobic metabolism; further, they synthesize various molecules and vitamins required up by our cells that we can’t make ourselves.

In our guts, microbes thrive in the outer layer of mucus. This outer space is actually considered outside the body (since the GI tract is basically a hole from your mouth to anus) and is called the lumen. In this dark void, microbes either live as free-floating colonies in the luminal gel or can attach to the top mucus layer. Some species even embed their colonies into the mucus layer which has dangers of its own as research is showing that viruses who prey on microbes seem to really like the shadow lands of the mucus layer[i]; however, the mucus immediately near the gut epithelial cells remains microbial free in a healthy individual[ii].

There are about 1 million microbes per milliliter in the small intestine and possibly 1000 times more in the colon with 100 times that of viruses in the system as a whole. As I mentioned earlier, they all survive by binding to specific carbohydrates in the viscous layer of the mucus. Microbes usually find purchase in the flowing mucus by grabbing hold of the carbohydrates (think of these as dangling chains made of sugars that microbes can attach to) that form the mucus structure. In the gut, our human genetics can dictate to some extent which microbes attach and colonize the gut by manipulating[1] the types of carbohydrates in the mucus—sort of like shaping the land to be more attractive to settlers who like rocky desert or soft earth or sandy beaches better. However, microbes are wily and will scrabble to grab anywhere that works; they’ll settle in the desert even if they long for the beach. Once they have a potential site for a new home, microbes can facilitate their expansion[2] in the gut after initial colonization by secreting carbohydrates that act as anchors to allow other daughter cells to bind to the mucus, so eventually, a large colony can terraform our gut into the place they want. Thus a family legacy can be established, with the sheer numbers of the microbial family as well as secreted defense molecules pushing out any other microbes that might try to break into that particular niche.

As the three factors of abilities, energy, and predation shift and change over time, the microbial colony changes too. Sometimes a daughter bacterial cell can acquire a mutation in her genetics or even an additional set of genes that renders her different from the rest of the colony. With that change, this microbe can abandon its current niche and move to another with a snap of her flagella[3]. As you can imagine, this constant flux—the flow of mucus, changes in food, changes to surface attachment sites for the microbes, recruitment of new microbes, exclusion of others—leads to communities that change over time.

[1] Every human biont has genetic influences that determine the structure of his or her mucus. This specificity can influence which microbes, traveling through the gut, can build their home there.
[2] By expansion, I mean that the colonizing microbes divide like crazy, creating millions of genetically identical daughter cells which comprise a single colony and ecological niche.
[3] Actually most microbes in our gut have lost the genes for motility their hardy cousins who live in the wide world have. But it’s fun to think of their snapping their flagella.
[i] Jeremy J. Barr et al., “Bacteriophage Adhering to Mucus Provide a Non–host-Derived Immunity,” Proceedings of the National Academy of Sciences, May 20, 2013, doi:10.1073/pnas.1305923110.
[ii] Johansson et al., “The Inner of the Two Muc2 Mucin-Dependent Mucus Layers in Colon Is Devoid of Bacteria.”

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