The Way of the Holobiont: a Simple Model

Lynn Margulis, the mother of all holobionts. 

The concept of holobiont has several definitions, the simplest one being "any symbiotic system." But that definition tells us little of what makes holobionts tick and it is often arbitrarily limited to microbial systems. The concept of "holobiont" is wider, and it is based on a functional definition: a holobiont is anything that behaves as a holobiont, that is, in terms of the interactions among the creatures that compose it. Here, the master trick is symbiosis, intended as a win-win interaction extended at the network level. In holobionts, all creatures are linked to each other (directly or indirectly) in a network of interactions that involve advantages for all the creatures involved. Holobionts are the result of natural selection that favors those holobionts that can obtain homeostasis -- the stability that allows them to survive and, hence, win the evolutionary game. 

But how is this win-win mechanism? It is best explained by an example. Many kinds of systems, even non-biological ones, can function in the same way as microbial holobionts. So, the simplest network I can think of as an illustration of the holobiont mechanism is a flock of birds. Every bird communicates visually with other birds. There are several fascinating models of how bird flocks fly, but here let's see an even simpler system: birds foraging in a field. One bird sees something suspicious, it flies up, and in a moment, all the birds are flying away. There you go: 

 

You can see in the figure the fitting of the number of flying birds as a function of time using a logistic function.

The mechanism of this interaction is simple: one bird detects a predator and flies away. The message arrives to all the other nodes of the bird network as a "meme" a basic unit of communication. The meme "a predator is nearby" spreads all over the network and rapidly all birds fly away. Note that the bird that sees a predator acts only in view of its own survival: it does what it would do if alone. But all birds benefit from the bird acting as a "sentinel." It is a win-win strategy. Incidentally, human beings tend to do the same. A human crowd has two basic states: "calm" and "stampede." But even humans can be said to have just two states according to the principle proposed by James Schlesinger: complacency or panic. 

Let's try now to model this behavior. We can use the "SIR" (susceptible, infected, removed) model, well known in epidemics. We call "S" the number of "normal" members of the bird population, I the number of panicked ones that flew away. R is the number of birds that recovered from panic and alighted again. 

Here are the equations of the SIR model: 

S'=- k1SI

I'= k1SI-k2I

The apostrophe symbol indicates the first derivative with respect to time. The k(s) are positive constants.  There is a third equation for R, but we don't need to write it since R' is simply equal to k2I.

This system doesn't have an analytic solution, but it can be easily solved iteratively. The result is the typical bell-shaped curve observed when an epidemic flares in a population. 

Note how not the whole population is infected; a fraction remains untouched. They have a "natural immunity" -- in this case a memetic immunity. This fraction can be calculated as approximately equal to k2/k1 (take the second derivative of S, and approximate I =0 for t>>0). The meme will diffuse more the larger the diffusion factor, k2, but that will be hampered by the decay factor, k3. 

The system is evolutionary. The k2/k1 ratio is calibrated in such a way as to optimize energy consumption: every bird that flies consumes a certain amount of metabolic energy that has to be compared with the energy that the flock would lose if one or more birds were not to fly. 

In general, for a flock of birds, the k2/k1 ratio is large, but it doesn't mean that all birds immediately fly away when they receive the "predator" meme. See this clip (featuring my grand-daughter, Aurora): 

You see that pigeons in a public park are much more difficult to scare than wild birds in the open. They have learned that humans aren't so dangerous, so the meme "a predator is here" doesn't generate the same quick flight response as the other video above. It is a case of "memetic herd immunity."

These are just initial notes on how the concept of "holobiont" is strictly linked to the network structure that creates it. Some network structures are much more complex than the simple "lattice" ones formed by a flock of birds or a herd of herbivores. A general theory that classifies these structures is the "Integrated Information Theory" (IIT) proposed by Giulio Tononi and others as an explanation of the phenomenon called "consciousness." 

Personally, I am not sure if consciousness can be measured in terms of the "phi" function proposed by Tononi, but the idea has interesting applications with holobionts since it deals with how many states a network can have. A flock of birds can have just two states, a human brain... well, let's just say a large (hugely large) number. So, holobionts could be classified in terms of their Phi value according to IIT. But this is a complicated subject that deserves to be discussed in more detail in another post. 

Can Holobionts Love Each Other?

Two holobionts enjoying each other's company. Sara peacefully sleeps in the "arms" of a beech tree on the Amiata mountain. She is obviously happy to be embraced in this way; we are tempted to think that the tree thinks the same.

Do trees perceive the world around them? Absolutely yes, but in a very different way from how we humans do. Trees have no eyes, no muscles, no above-ground nerves. But they perceive chemical signals, light signals, vibrations, and, probably, things that we don't even imagine could be perceived. So, the tree gently holding Sara cannot "see" her. But it can perceive her presence in the form of vibrations and chemical signals. The tree perceives Sara more or less how we could perceive a ghost. 

And what does the tree think of Sara? The brain of the tree is below ground; it is the vast network of connections of the root system, boosted by the help of fungi. It is called the mycorrhizal system. Maybe this alien brain can form an image of the strange creature resting near its trunk, although, for us, it is nearly impossible to understand in which form. Maybe the tree is asleep, too. And what does it dream? We can't know, just as we can't know what Sara is dreaming. The only thing we can say is that there is no reason to think that holobionts can't be in love with each other. 

h/t Sara

The Brain, the Gut, and How we get Old

A message sent to the "Proud Holobionts" forum. If you are interested in joining it, write at prudentlobster(thingette)gmail.com. Image from the Leverhulme Center for the Holobiont (yes, there exists such a thing!!)

Dear colleagues,

while every day humans demonstrate more and more their stupidity in the way they deal with each other, there is still such a thing as "real" science that moves onward. I found a recent paper by Dilara Hasavci and Thomas Blank of the University of Freiburg, Germany, that I think may be of interest to you at:

https://www.frontiersin.org/articles/10.3389/fncel.2022.944526/full

I do not claim to have been able to able to read and digest the whole paper, but it is surely fascinating. It is about how the health of the human brain is correlated to the gut microbiota. It sounds strange: why should these two organs be so strictly related to each other? And, yet, the brain is far from being a squishy version of the central processing unit of a computer. It is continuously kept, managed, maintained, repaired, and upgraded by a hugely complex system of specialized cells, mainly the "microglia," but also a host of macrophages: the authors say:

"Parenchymal microglia and perivascular, meningeal, and choroid plexus macrophages, representing non-parenchymal CNS-associated macrophages (CAMs), are among the innate immune cells of the brain (Kierdorf et al., 2019). Together, they significantly influence cerebral inflammation and can be targeted by gut-derived metabolites, especially with increasing age (Mossad and Blank, 2021). Activities connected with macrophages' highly developed lysosomal compartment are among their main tasks. Microglia and macrophages express a number of receptor families that help them degrade old, necrotic tissues and harmful substances from the circulation and their surrounding milieu (Prinz et al., 2017). The CNS is usually only mildly affected by transient activation of brain macrophages. Aging, on the other hand, is associated with chronic systemic inflammation and persistent brain macrophage activation, which can cause major physiological, behavioral and cognitive dysfunctions"

Surprisingly, or perhaps not, this apparatus is deeply affected by the gut microbiome. The connection is through the blood circulation system:

"Studies in germ-free (GF) mice revealed the importance of the microbiome in microglial development and maturation, as well as function in the adult brain. Microglia from adult GF and specific pathogen-free (SPF) mice display different morphologies including branch points, dendrite length, segment number, and cell volume. Additionally, the transcriptomic profile of microglia in GF mice shows a downregulation of several genes involved in cell activation and induction of immune response (Erny et al., 2015). The lack of mature gene expression in these microglia is linked to the absence of microbiota in the gut intestinal tract and disrupts their ability to respond to immunostimulants"

and

"Countless bacteria, viruses, yeasts, bacteriophages, and fungi inhabit our bodies. While microorganisms can be found on almost all environmentally exposed surfaces of our body, the gastrointestinal tract (GIT) shows the highest number and density of microbiota. These communities have significant impact on numerous physiological mechanisms, such as function of the immune system and metabolism (Zhuang et al., 2018; Dabke et al., 2019). The gut modulates several functions in the brain by bacteria-derived metabolites, hormones, and neuroactive substances reaching the CNS via the vagus nerve, enteric nervous- and circulatory system, and immune system"

And finally, note that

"Several studies have found that microbial metabolites can affect gut–brain responses, affecting the morphology and function of brain macrophages. These changes include their polarization and phagocytic capacity, which, in turn, controls behavior and emotional processes."

In short, the way we get old strongly depends on our gut microbiota. It seems also probable (although they do not say it in this paper) that the fact that some of us lose our brain capabilities with age also depends on that. I was just discussing today with a distressed colleague whose mother (88 years old) is going down the dementia road -- and yet, my wife's mother reached 101 years old without losing her mind. Is it all due to the gut microbiota? It would be wonderful if we could cure dementia with gut bacteria but, as they say in the paper,

" A roadblock in today's microbiota-based biomedical research is the modest and long-term impact on psychological and cognitive performance. Probiotic and microbiota-based therapies may take months to years to affect neuropsychiatric illnesses"

So, there are many things we still don't know about this story. It is another facet of the complexity of holobionts.



U.B.