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.

What makes us holobionts: Touching each other as a gift of love.

Image from Nella Turkki's dance project, "I, Holobiont"

 

Touching each other is part of what makes us fellow holobionts, part of the greater holobiont that we call the Ecosphere or, sometimes "Gaia." In his book, "Thank God for Evolution," Michael Dowd doesn't mention the term "holobiont," but he gives us a poignant description of what it means touching each other, starting at page 231

The Furry Li'l Mammal in each of us craves touch and tenderness. Without touch, a baby dies, the human heart aches, the soul withers. Touch is not only a biological need; it is a profoundly elegant and essential form of communication. . . . For millions of years our mammalian ancestors were reassured by parents or comrades not through words but through touch. For 99.9 percent of our mammalian journey, there were no words. The need for touch begins for mammals at birth and continues until we die. . . . There is healing in touch, too. Because tender touch communicates love and care, it triggers metabolic and chemical changes in the body that assist healing. Touching also stimulates the production of endorphines -- natural body hormones that control pain and embrace our sense of well-being.

And, let me add, touching each other means exchanging our skin microbiota: it means exchanging the skills that the small creatures that populate our skin use to protect us from harmful creatures and chemicals. Touching each other is a reciprocal gift, it is a gift of love.

Onward, fellow holobionts!  

_______________________

Below, you see the front cover of Michael Dowd's beautiful book "Thank God for evolution" (2008). But if you want to know why exactly ancient Christians used a fish as a symbol of their faith, you have to read the book by myself and Ilaria Perissi "The Empty Sea" (in Italian), or wait for the English version to be published by Springer (should be soon)