For several years now, the microbiome has increasingly come into the public eye. The billion of bacteria, that live in our bodies have a previously underestimated influence on whether we are more healthy or sick. The exact connections are not yet fully understood, but one thing is certain: We live in a close symbiosis with our bacteria.
The better we understand this interplay, the better we can make use of it. If we eat a lot of z.B. plant-based fibers our gut bacteria can convert these into short-chain fatty acids that come with some health benefits.It is also health-promoting to maintain as much diversity in the microbiome as possible.
With age, this symbiosis increasingly seems to become a dysbiosis . Fewer and fewer of the "good" bacteria live in our intestines, and the "bad" ones are taking over. This cannot simply be broken down to one type of bacteria, as each microbiome is highly individual and depends on many factors, such as diabetes, cardiovascular diseases, and cancer. Here you can find everything about the topic.
More than just bacteria – our microbiome
About the microbiome entire books can be filled. Hardly a day goes by without a new study being published on the topic. And the research interest is more than justified. The microbiome relies on us and vice versa. How exactly this symbiosis works is gradually being uncovered. In very rough terms, we can say that we need the microbiome to access certain nutrients from food. Our body does not have the right enzymes to break down every nutrient. And this is where the microbiome comes into play.
What would normally be considered "waste" for us, such as z.B. fiber, can be digested by our microbiome.Bacteria even rely on us to "feed" them. In return, they produce some substances that are beneficial for our health. These include secondary bile acids, vitamins, amino acid derivatives, and short-chain fatty acids.
Furthermore, the microbiome seems to be closely linked to our gut nervous system – a gigantic network of nerve cells that surrounds our gut along its entire length. If you will, our second brain or our "gut feeling". And this enteric nervous system is, of course, also in communication with our central nervous system.
So you can already see, the microbiome is complex and its connections or effects are even more complex. This makes it not always easy to conduct studies.Nevertheless, the scientists were able to find out quite a bit regarding aging. More on that shortly.
It's all about diversity – symbiosis instead of dysbiosis
Before we look at what happens when the microbiome does not work to our advantage, we must ask ourselves the question of what a healthy microbiome is. This question is more difficult to answer than one might assume at first glance. There are countless studies on this, and the insights can be defined as follows: The microbiome is very individual. What bacteria did we carry over from early childhood? In which country were we born? What genes do we carry within us? What did our diet look like in childhood? Did we have severe intestinal infections? How do we eat? Do we consume a lot of fiber? And so on.
It is widely recognized, that we develop our microbiome in early childhood and that it generally remains stable throughout our adult years (unless one radically changes their lifestyle or environment).
The older we get, the more the diversity of bacteria in our gut decreases. Researchers see this as one of the main reasons for age-associated diseases. A one-sided microbiome makes us susceptible to an excess of "bad" bacteria.
This can be impressively seen in the example of Clostridium difficile . This small bacterium lives in our gut and initially does not cause much commotion there.If we have a stronger infection that requires a specific antibiotic treatment, this bacterium, however, has a survival advantage. While a large part of the bacteria in our intestines dies off, C.difficile survives and begins to multiply rapidly, as suddenly there are no more competitors. The result is a severe intestinal infection that often needs to be treated in the hospital.
A dysbiosis can be triggered by the overpopulation of the bacterium Clostridium difficile. This is often caused by antibiotic therapy.
Dysbiosis using p-Cresol as an example
There are hundreds of metabolic processes that all have a potential impact on our health.To simplify things a bit, we will show you an example of a well-researched metabolite: p-Cresol
In the ELDERMET study , 500 people, all over 65, were tested for their microbiome and possible metabolic products. It was found that participants with higher stool concentrations of p-Cresol exhibited increased frailty.
So what is p-Cresol? This molecule is produced by the fermentation of the amino acid tyrosine in our gut. The sulfated version of the molecule is excreted through our kidneys. As long as our kidneys are healthy, this does not seem to be a problem. However, if the filtration rate decreases and the p-Cresol level in our blood rises, it seems to become problematic.
High p-Cresol levels are associated with the development of cardiovascular diseases and they have a toxic effect on the filtering system in our kidneys. This seems to be a vicious cycle. People with poorer kidney function often have a dysbiosis of the microbiome. There is an increased presence of aerobic bacteria that promote the production of toxic metabolites, including p-Cresol. Perhaps this hides a potential target for the future.
Tryptophan metabolism: From symbiosis to dysbiosis
Another important metabolic process in our gut is the Tryptophan pathway. Tryptophan is an amino acid that we z.B. obtain through food.Our gut bacteria have various ways to metabolize this amino acid. We show you the three most important ones:
- Kynurenine pathway (Kyn): Through the enzyme IDO (Indoleamine-2,3-Dioxygenase), tryptophan is broken down into kynurenine
- Serotonin pathway: Our gut bacteria can convert tryptophan into the "happiness hormone" serotonin. A full 90% of our serotonin is located in the gut! Through this axis, tryptophan can also be converted into melatonin, the sleep hormone.
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Indole pathway: The third way of tryptophan degradation is the indole pathway.Higher indole concentrations in older people have been associated with increased fitness. In mice, an increase in indole metabolites has also been shown to extend lifespan. Dysbiosis as a hallmark of aging: It's all about balance. Some studies regarding tryptophan metabolism conclude that a disturbance of the balance can contribute to diseases. If the aforementioned enzyme IDO (to be precise, the subclass IDO-1) is overactivated, we find more kynurenine compared to serotonin than normally present in the body. This excess of kynurenine is associated with certain diseases.It has been shown that depressives often have an overactivation of IDO-1, which results in lower serotonin levels. One of the hypotheses is that this contributes to depression.
Note: the long-held hypothesis in science that low serotonin levels are the trigger for depression is not entirely correct. Serotonin plays a role in the disease, but it cannot be simplified so easily.
Chronic inflammation can increase IDO activity and thus it can be hypothesized that inflammation also contributes to the dysbiosis of our microbiome in this way.
Inflammaging and Dysbiosis – two hallmarks with a close connection
As we have just seen, a chronic inflammation can negatively affect our microbiome. However, it also seems to go the other way around, at least experiments on mice suggest this. For this, two populations of mice were taken. One group consisted of young and healthy mice, and the other group consisted of older, sick mice. Now, the microbiome of the older mice was transferred to the younger mice. The result was that the younger mice showed significantly more signs of inflammation, meaning higher inflammation markers.
Conclusion
The microbiome is one of the most exciting fields of research, and the disruption of balance seems to contribute to several diseases in old age. We are losing the diversity of bacteria that keep us healthy, and therefore dysbiosis has also been recognized as one of the Hallmarks of Aging. In the future, we will certainly see some therapeutic approaches that aim to restore this dysbiosis.
The next article in this series will focus on the twelfth hallmark of aging: Altered Autophagy.
