A Good Holobiont has a Good Immune System. Managing your Microbial Environment

 

An incredible book by Philipp Dettmer: an ambitious attempt to tell the whole story of the human immune system in an understandable form even for the non-specialist. The result is a 345-page tome, lavishly illustrated, and written in an entertaining style. Remarkably well done, but not easy to digest nevertheless. I went through the whole thing once, but I need to restart from the beginning and reread it again. And, probably, I'll need a third pass. Afterward, I may be able to say that I know just a little bit about how the immune system works. 

And think that this is just an introduction that neglects or just mentions several important details. For instance, it mostly skips the role of the microbiome. But that must be hugely important: after all, human beings are holobionts. We can't survive without our microbiome, and it is likely that the huge numbers of small critters that populate our body play a fundamental role in managing the microbial system "holobiont-style." It means that the immune system is not a sort of Nazi militia that shoots down everything it doesn't recognize and doesn't like. It must be able to recognize those parts of the microbiome which are helpful and those which are not. And note that, in some cases, the same species of microbes can play the role of pathogen or symbiont, depending on the general conditions of the rest of the system. That's how good holobionts behave: they adapt to each other. We need to be colonized by microbes in order to survive. It is just a question of being colonized by the good ones. And it is the job of the immune system to ensure that it happens!

Amazing, as I said. It gives you a glimpse of the immense complexity of just a section for the even more immense complexity of the ecosystem -- that some call "Gaia." The goddess gave every one of us a complete defense and management system that kept our ancestors alive for the past 400 million years or so as multicellular organisms, and also a few billion years as single-cell organisms. If we are here, it means that the immune system of our ancestors worked well enough to interact with, and protect them from, the zillions and zillions of microscopic creatures that we eat, inhale, or come in contact with one way or another. 

But, wait.... aren't we supposed to be much smarter than Gaia, that poor old lady? We are so smart that we discovered that we can do better than just relying on that old stuff that uses billions of antibodies, t-cells, macrophages, and more. You know, those squishy things that evolved over a few billion years, what are they for? Instead, just a piece of cloth placed onto your mouth and nose, and -- voilà -- NOW you are safe! 

My Neighbor Holobiont

The most beautiful scene ever created. From Miyazaki's "Tonari no Totoro" (My neighbor Totoro). The true spirit of the holobiont is caught in this scene.

Be a Good Holobiont! Cultivate Mushrooms!

 

A mushroom-based lunch at the class on mushroom cultivation that I attended. The main dish is based on Pleurotus and I can tell you that it was absolutely delicious. Gaia is wise and benevolent in many of her manifestations!

I took a 2-day full-immersion class on mushroom cultivation. I am not sure that I can engage in this activity myself, it is a full-time job, not really suitable as a hobby. But it is surely a welcome respite from the daily, horrible news we are receiving from all over the world. It is fortunate that there are still people who spend their time doing something good and useful, and may Gaia bless them for what they are doing!

Mushrooms are not holobionts themselves, but they are part of many holobionts, not least forming the "rhizosphere," the all-important layer that keeps Earth's "skin", its fertile soil alive. And you may know that fungi are symbionts of the human organism, even though their role is still largely unknown. https://www.sciencedirect.com/science/article/pii/S1369527416301813

To know more about mushroom cultivation, see the site of the "Funghi Espresso" company that cultivates mushrooms using used coffee grounds as substrate. 

New Mysteries of the Human Microbiome: Cancer and Fungi

 

The idea that cancer is caused by a fungus, or that it may even be a form of fungus has been proposed by the Italian physician Tullio Simoncini. His ideas have been thoroughly demonized and Simoncini himself has seen his license of practicing medicine revoked. 

Now, don't make me intervene in a matter of which I know very little and, for sure, I am not saying that Simoncini is right. I am just noting that, after what we saw happening with the COVID19 story, the demonization of everything which is not "official" in medicine should be taken with a lot of caution.

The thing which I think matters is how complicated things are in everything that has to do with human health. Cancer is normally described as a mutation that makes cells lose their discipline and start reproducing wildly. Things are not so simple as that, I think. The human body has defenses that can rapidly get rid of any rogue cell and it is strange that these defenses become ineffective when dealing with tumors. And, indeed, the story of cancer growth is much more complicated than that. 

Simoncini may have had an interesting intuition when he proposed an important role of fungi in human cancers. You can read the story in this recent paper

https://www.cell.com/cell/pdf/S0092-8674(22)01127-8.pdf

which is structured as a headache machine from the first ten lines of text. Nevertheless, I think the point it makes is clear: all the cancer types the authors studied had some fungi associated with them. That is a new piece of information that goes in parallel with the fact that cancers also harbor special bacteria. What is the role of this microbiome? Nobody knows and, correctly, the authors state that "they have not established causation," even though it seems that the presence of fungi is, sometimes, associated with more aggressive cancers.  

I think it is possible to say that cancers are holobiont-like assemblies of cells, bacteria, and fungi. If they are, that could explain their resilience and their stubbornness. Holobionts are machines that optimize their own survival, and, in this case, it is unfortunate that the cancer holobiont doesn't seem to care about the survival of its host. Maybe, in the future, we'll learn more about this subject and perhaps we'll find a way to exploit this knowledge to help people who are struck by cancer. For the time being, we can be awed, as usual, at the incredible complexity of life in all its forms. 

More discussions on cancer and fungi at

https://www.algora.com/Algora_blog/2022/10/02/7787

https://www.nature.com/articles/d41586-022-03074-z

https://www.healthline.com/health/is-cancer-a-fungus

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.

The Krebs Cycle: The Origin of Life?

 

You probably know Nick Lane for his books, such as the rather famous (among some slightly nerdy people, I read it twice!!) "The Vital Question." An older, but still interesting, book by Lane is "Oxygen, the Molecule that made the World."

Nick Lane was recently interviewed on "Nautilus" about his new book, "Transformer: the Deep Chemistry of Life." It is about the Krebs cycle, the engine that powers all the holobionts on this planet. Here, Lane describes how we may be finally cracking the mystery of the origins of life: an epochal discovery. You probably remember how, in the 1950s, it was discovered that the so-called "primordial soup" could generate aminoacids when exposed to ultraviolet rays or electrical discharges. Then, it became fashionable to think that life could have developed on Earth as the result of the assembling of aminoacids to form DNA or RNA molecules. It also became fashionable to think in terms of the "RNA world" that may have preceded the current molecular structure of cells.

Alas, it didn't work. Aminoacids stubbornly refused to assemble themselves into anything more than short-chain peptides, molecules akin to proteins, but much simpler and smaller. This field was gradually abandoned for lack of success in obtaining any useful results about the origin of life. . But now, Lane is reconsidering the idea with a new take: trying to see if it is possible to self-assemble the Krebs cycle or at least something that resembles the Krebs cycle. (Image from Wikipedia)

Fascinating story. I am going to order Lane's new book, even though I don't guarantee that I am nerdy enough to read it twice (maybe not even once), but I'll try.

And, as usual, onward, fellow holobionts!!

The Role of the Forest Holobiont in Earth's Climate: More Important than it was Believed so far

Above, the talk by Anastassia Makarieva at the International Conference on Basic Science for Sustainability in Belgrade, on Sep 22, 2022

It is about an innovative and important interpretation of the current climate situation. Anastassia is proposing that the warming of the atmosphere may be caused not just by the accumulated CO2, but by a radiative forcing of the same order of magnitude generated by deforestation. Earth's forests are giant holobionts coupled and embedded in the even larger holobiont that's the whole ecosystem. It is not surprising that they strongly affect climate, and not just by the conventional factors, albedo and carbon sequestration. There is much more than that, as you can learn by watching the clip, above.  

I don't have to tell you the consequences of this concept. If it turns out to be true (and I think it might well be), it means that we have done a lot of wrong things in trying to mitigate global warming, for instance proposing "biofuels" obtained from wood. But there is much more: it is a complete revolution in the way we see Earth's climate system. Forests not only cool the atmosphere, but also stabilize the climate. This means not only that we need more forests, but that some ideas such as carbon sequestration and geoengineering could do a lot of damage if not coupled with reforestation.

On the other hand, Anastassia's ideas could also be misunderstood as meaning that Climate Science, as it has been proposed so far, is all wrong. And that's sure to happen if her ideas come into the hands of politically minded people who would use that to propose that there is no such thing as global warming, climate emergency, etcetera.  But if we believe in Science (true science, not TV science) we must not be afraid of the truth.

Onward, fellow holobionts!