Can our bacteria and virus friends save us? The rise of psychobiotic therapies for the human holobiont

 

The effect of the gut microbiota on the brain in the human holobiont is an incredibly complex story. It is described in a review appeared in 2019 on the "Physiological Reviews" journal. Not so much a review as a whole treatise, it is huge, with 1694 references in the bibliography!!! You can find a more readable summari on the blog "gut microbiota for health"

Before going on, a note of caution: as it is the rule nowadays, most of what appears in the medical literature is biased or simply false as the result of the widespread corruption of the medical research system. This review has been partly sponsored by the pharmaceutical industry, nevertheless it seems reasonably free of hype for specific treatments or wonder drugs. Its approach is correctly evolutionary, for instance when they say:

"Given that there has never been a time when mammals existed without microbes (apart from under highly restrictive laboratory conditions), there has also never been a time when the brain has been without signals from the gut, and it is important to consider the relationship between the host and its microbiota from an evolutionary perspective"

And they have it perfectly right when they use the magic word "holobiont"!!!

"The hologenome theory may even account for complex biological phenomena such as certain behaviors. For instance, behavior that facilitates social interaction among holobionts might be considered evolutionarily adaptive/advantageous as it gives rise to greater transmission of microbiota, thereby enhancing genetic variation (1285, 1286, 1689). In light of these inextricable links between the microbiota and the brain throughout evolutionary history, it is imperative for the study of our own biology (and that of the entire animal kingdom) to understand how microbial symbionts influence brain physiology and behavior."

The main point of the paper is that the human brain is strongly influenced by the gut, that our behavior, to the point that modifying the gut composition can be seen as a form of "psychobiotic therapy" that improves plenty of pathological situations and improves also the quality of life, for instance helping against depression. 

Seeing how the world is behaving nowadays, it would seem that the human microbiome is in bad conditions, indeed. Especially the gut of our leaders seems to have been invaded by micro-monsters instead of the beneficial gut flora that's normal for humans. And, surely, the various habits of hyper-cleaning, distancing, and self-suffocation that became fashionable during the past two years didn't help in improving the situation. Maybe, at this point, only our bacterial and viral friends can help us (with a little support also from our friendly archaea and fungi). Go, friends, go! We need you badly! 

The epidemic of obesity keeps getting worse. What's a good holobiont supposed to do?

 

The obesity epidemic keeps expanding. The above are, I believe, the most recent data available for the US. The COVID-19 lockdowns and isolation measures are reported having made things even worse. This trend is simply horrendous: what the heck is happening to humankind? (Disclaimer: I am not a nutritionist, I am just someone who is fascinated by data and trends. And, of course, we are all interested in our health! Here, I report some data I found, hoping you may find them useful. Don't take them as the last word on the subject. As always, before acting on things that affect your health, do your own search and use your judgement about what works for you.)

The obesity epidemics had a considerable boost by the lockdowns during the Covid-19 pandemic. Coupled with the opposite effect, that obesity is a risk factor for people who contract Covid, you have a remarkable disaster in the making. With several Western countries having percentages of obese people close to or higher than 50%, one wonders what's going to happen in the future. Why are the human holobionts in such a poor shape?

The story is complicated, and I don't pretend to say anything new. I just want to attract your attention to some recent studies that I think shed some light on the mechanism of human obesity (but even our fellow dog holobionts are suffering from obesity). 

First, the work by Raubenheimer and Simpson on the food preference of various animals, summarized in a recent book titled, "Eat like the Animals." (Mariner Books, 2021). Their discovery is easy to summarize: it seems that most living beings have a specific set point in their needs for the main nutrients. They seek for a specific balance among proteins, fats, and carbohydrates. In particular, they aim at a minimum intake of protein. If animals are fed an unbalanced diet, for instance, poor in protein, they will tend to eat more food until they reach the right level. Raubenheimer and Simpson call this the "protein leverage hypothesis:" 

"In a protein-poor but energy-rich food environment, humans will overeat carbs and fats to try to reach their protein target. However, when the only available diet is rich in protein, human will underconsume carbs and fats"

Since excess carbohydrates are stored in the body as fat, we can say that one of the causes of the obesity pandemic is that the human diet in Western countries is overstocked in carbohydrates. 

Here comes Robert Lustig and his book "Metabolical" (Yellow Kite 2021) where he minces no words on how this is not only true but also a profitable strategy for the food industry. They discovered long ago that if they put more and more carbohydrates (sugars) in the food they sell, then people will get fat, they will eat more, and that will increase their profits. Just like sick people are a boon for medical doctors, obese people are a boon for food producers. 

You don't believe that? Let me show you a picture I took a few days ago in an Italian supermarket:

There are four kinds of regular mayonnaise on sale, plus a fancy one with no eggs. Can you guess which is the only one that does not contain added carbohydrates? Let me tell you, it is the most expensive one among the regular ones. All the others contain sugar. Maybe it is not the same for all mayonnaise brands on the market, but I think it is significant. Food companies do add sugar everywhere, even when it is not called for by the traditional recipes. They deny that, but it is written on the list of the ingredients (I have pictures, if you don't believe me!)

Now, it may well be that there is much more to obesity than just carbohydrates, but I think that these results point at an important cause of the problem. There are data showing that what we are seeing may be a delayed effect of "peak sugar" that occurred around the year 2000. From then on, the amount of sugar consumed in the U.S. has been going slightly down. But it remains high. 

The beauty of this is that, if it is true, with obesity we don't have such a wicked problem as others, say, global warming. We know that to avoid global warming, we should stop burning hydrocarbons, but it is also true that we can't just stop: billions of people would die. But we could stop, or at least strongly reduce, the extra carbohydrates added to processed food, and we could do it today. Nobody would die, but the problem would be eased and many people would be healthier! But this is the way things are in the world: no problem can ever be solved when there is somebody making money if it remains unsolved. 

To make you happier, let me show you some data that tell us that a little excess weight (a little!) is not necessarily bad for your organism. Here are some data from Malcolm Kendrick's wonderful book "The Clot Thickens" (Columbus 2021). 

BMI stands for "Body Mass Index" and the overall lowest risk of death is for a BMI of 25-30 that's normally classified as "overweight" (if you want to know, I am at BMI=27). Being underweight is a larger risk than being obese! But obesity has many other problems, not least in terms of self-esteem. 

In the end, remember that you are a holobiont and that for hundreds of millions of years your holobiont ancestors never ate anything that was processed in an industrial plant. You are a fine-tuned machine that includes trillions of friendly viruses and bacteria living in your guts. They want a balanced diet of fats, protein, fiber, and not too much in terms of carbohydrates (but you need them, too!). Try to make them happy, and you'll be happier, too!

Gaia's One Billion Years Task: Colonizing the Land

 

Gaia as the sea Goddess Grammamare according to Hayao Miyazaki's interpretation in the film "Ponyo"

Imagine a time machine that brings you back to the Earth of one billion years ago, right in the middle of the eon called the "Proterozoic." First of all, you need an oxygen respirator, otherwise you'll die of suffocation in a few minutes. You also need a wide-brimmed hat and an outfit that covers your limbs in such a way as to protect your skin from the ultraviolet radiation. It is your planet, but in this period it is not especially friendly to a metazoan as you are.

You walk a few cautious steps onward. In front of you, the blue sea. You turn around: an expanse of dry rocks that continues all the way to the horizon. No traces of anything green that you can see: no plants, no insects, no birds, nothing like that. Above you, the sun is bright in the blue sky. You notice that it is a little less bright than you are used to seeing it, in your time. No traces of clouds: it is what you expected: no trees means no evapotranspiration of water vapor, no volatile organic compounds to function as nucleation sites for the water droplets that form clouds. 

You walk toward the sea. There are mainly rocks, but also some sandy places: small patches of beach. If there is a beach, there has to be a river, somewhere, that created it. You see it, not far away. It is completely dry, its bed going straight through the rocky landscape from the hills in the distance. Rains, when they arrive, must be torrential downpours that come and go quickly. 

You kneel on the beach, in front of the sea, lifting some water with your cupped hands. You know that it should be less salty than the seawater you are used to in your time, and you are tempted to taste it to confirm. But that is not a good idea. That water is brimming with microorganisms, most of them unlike anything your immune system is used to. You drop the water on the surface of a rock, where it forms a dark spot that rapidly evaporates and disappears. 

Standing up in front of that alien sea, you look at the gentle waves coming and going. You know that there are no fish in there. No crabs, no seashells, no seaweed, nothing like that. But there are enormous numbers of microorganisms. They are photosynthesizing, eating each other, reproducing by splitting themselves in two. They can live only in water. Is there life on the dry rocks on the shore? Maybe some of those microscopic creatures survive there, maybe even thrive, perhaps algae or even ancestors of modern lichens. But they are just eking out a precarious existence. They are invisible to the naked eye, and their time has not come yet.

On the horizon, an enormous orange moon rises as the sun slowly fades on the opposite side. You keep looking at the dark waters in front of you. Just under the surface, you glimpse something that looks like a pair of large eyes. You think you see her just for a moment, Gaia in her form of sea goddess, languidly swimming in the calm sea. 

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Back to your time machine. You dial 350 million years before your time, the start of the Carboniferous Period. You press the button. 

You emerge out of the machine, breathing the fresh air, smelling something you had never smelled before. Whatever it is, the air is humid, rich in oxygen. You are in a small clearing, in front of you, there is a pond surrounded by a lush forest. Trees, tall trees, forming a full canopy under the low clouds, swept by a gentle wind. The place is eerily silent: no birds, no insects, nothing like that. Yet, you recognize the place: this is your planet, Earth, not yet the way it will be in the future that is your time, but a familiar world. 

As you stand, a noise comes to you: a buzz. You see something flying away, an insect of some kind. It starts raining. It is a warm, gentle downpour that wets you rapidly, but ends quickly. It has been enough to disturb the creatures living under the low bushes. You have a glimpse of them scuttling away: tetrapods, early amphibians. They jump into the water of the pond and then disappear. They are your ancestors, the ancestors of all the metazoans that will move on land in the future that's your time. 

As you walk, splashing your boots on the mud, you wonder how Gaia pulled this incredible trick: transforming the bare rock of entire continents into lush forests. While you think that, you have a glimpse of a pair of bright eyes staring at you from the canopy. You look up, and they disappear, leaving only a Cheshire-cat smile of the Goddess of the Forests, then she vanishes among the branches.

Images of the Goddess courtesy of "Mon Seul Desir"