Microbiome - Fountain of Youth in the Gut?

How is my gut actually doing? This question is more present than ever, because the microbiome of our intestine is becoming more and more conscious and is now held responsible for many mechanisms in our body. Whether we live to a ripe old age is determined by many factors over which we probably have more influence than previously assumed. The latest research indicates that the intestinal flora is significantly involved in how long we live and which diseases we will contract.

In this article, we show you what the current state of research on the microbiome is, whether microbiome tests are worthwhile at all and what short-chain fatty acids, such as butyrate, have to do with health.

What is the microbiome?

To begin with, we need to briefly clarify what the microbiome actually is. Strictly speaking, we have different microbiomes. Wherever bacteria, viruses and fungi are found, we can speak of a microbiome. These are, for example, the gastrointestinal tract (especially the intestines), the skin, the mouth, the respiratory tract and the urogenital system.

In this article, we will mainly focus on the intestinal microbiome, our intestinal flora.

The tasks of the microbiome

The human microbiome is an inexhaustible field of research that produces new scientific discoveries every day. We are learning more about the inhabitants of our intestinal flora, the gut-brain axis and how diseases can possibly be treated via the microbiome. Without the symbiosis of our bacteria and the body, we would probably not be able to survive. For example, the microbiome is essential for the assimilation of certain nutrients from food. The human body alone does not have the full spectrum of enzymes needed to break down every nutrient.

Waste products and the gut feeling

The term microbiome is used synonymously with intestinal flora and refers to the entirety of microorganisms that colonize our intestines. What is often regarded as "waste" for the human organism, such as dietary fiber, serves as an essential food source for the intestinal flora. The microbial digestion of these substances is not only vital for the bacteria themselves, but also results in the production of metabolites that are of great benefit to human health, including secondary bile acids, vitamins, amino acid derivatives and short-chain fatty acids.

There is also a significant connection between the microbiome and the enteric nervous system - an extensive network of neurons that runs through the entire gastrointestinal tract. This is often described as the "second brain" or the physical manifestation of the "gut feeling".

Did you know?

Sugar substitutes are suspected of playing a role in insulin resistance, a precursor to diabetes mellitus. Originally, it was hoped that sugar substitutes could provide the sweet taste without the negative effects of sugar. However, this does not appear to be the case. In this study, the researchers were able to show that sweeteners can alter the microbiome and thus contribute to the development of the disease.

Research on the microbiome

The field of research into the microbiome is still quite young. One of the reasons for this is that many bacteria in our gut are strict anaerobes. This means that when they come into contact with oxygen, they die almost immediately. Researchers have come up with various ways of getting around this problem. One of these is the Human Microbiome Project.

Human Microbiome Project (HMP) - the starting signal for research into the microbiome

The Human Microbiome Project (HMP) was a groundbreaking initiative aimed at understanding the complex microbial communities that colonize the human body and their role in health and disease. Launched in 2007 by the National Institutes of Health (NIH) in the United States, it was one of the first major research programs to systematically address the human microbiome.

Aims of the Human Microbiome Project

The main objective of the HMP was to create a reference database of the microbiota inhabiting different parts of the human body, including the gut, mouth, skin and urogenital tract. By using state-of-the-art genomic technologies such as 16S rRNA sequencing and metagenomics, the project aimed to catalog the genetic diversity of microbial communities and understand their functions, interactions and impact on human health.

Important findings

One of the key findings of the HMP was the realization that the human microbiome is enormously diverse and represents a significant genetic resource that is essential for human physiology. The project revealed that microorganisms are involved in many important biological processes, including:

• Digestion and metabolism of nutrients
• Development and function of the immune system
• Protection against pathogenic microorganisms
• Influencing brain function and behavior

In addition, the HMP showed that changes in the microbiome are associated with a variety of diseases, including inflammatory bowel disease, obesity, diabetes, cardiovascular disease and even psychiatric disorders such as depression

Did you know?

The colonization of the intestinal flora is a lifelong process that begins at birth and only ends with death. In a study published in "Nature Metabolism", the intestinal flora of 9,000 people in an age group of 18 to 101 years was compared with each other. The researchers found that it is not only the human being itself that ages, but also the intestinal microbiome. In healthy test subjects over the age of 77, changes were observed in the intestinal flora, in which rare bacterial species dominated and the usual microbiome pattern decreased. This uniqueness was absent in less healthy test subjects.

Microbiome test - what options are there?

The desire for reliable microbiome tests also developed from the HMP. In the project, complete genome sequencing, also known as whole genome sequencing (WGS), was used for microbiome analysis. The advantage is that everything is analyzed, which is also one of the disadvantages. True to the saying "not seeing the wood for the trees", a WGS can provide too much information that we are not yet able to classify. Perhaps in the future it will be possible to better evaluate this wealth of information with the help of artificial intelligence.

Another disadvantage of complete genome sequencing is the high cost, both financially and in terms of the work involved. However, there are also other microbiome tests on the market:

Strain analysis of bacteria

Strain analysis of bacteria, often performed by 16S rRNA sequencing, focuses on the identification and quantification of specific bacterial species or strains in a sample. 16S rRNA gene sequencing targets a highly conserved region in the bacterial genome, allowing differentiation between different bacterial strains. Think of it like a barcode. Each bacterium has such a barcode (the 16S rRNA) and for each bacterial species this barcode always varies slightly. This allows researchers to distinguish between different types of bacteria.

Did you know?

A brief explanation of the terminology. Bacteria are divided into families and strains. The first part of the word represents the family name, e.g. Bacillus, and the second part of the name represents the strain, in this case Bacillus subtilis. Even if this name sounds more like a pathogen, Bacillus subtilis is enormously important for our health. It was even voted "Microbe of the Year 2023". You can find out more about this exciting bacterium in our article on QBIOTIC.

Further microbiome tests

In addition to those already mentioned, there are several other tests. Shotgun metagenome sequencing and metaproteomics are still widely used. Compared to 16S rRNA gene sequencing, the former offers the advantage that other organisms such as viruses or fungi are also included. Metaproteomics does not look at genetics, but at the proteins produced. This field of research, also known as proteomics is one of the most exciting in the field of personalized medicine and longevity. Compared to epigeneticswhere the markers on the DNA are measured, proteomics looks at the proteins produced. MoleQlar's latest test, which allows you to find out your molecular profile, is also based on this. In collaboration with the renowned LMU Munich, we offer you a deeper insight into your molecular self.

It's not just the genes

The field of research on the microbiome is highly complex and is characterized by many influences. One interesting example is the bacterium Eggerthella lenta (E. lenta) DSM 2243, a bacterium that occurs in the human intestine. E. lenta has an interesting interaction with the heart drug digoxin. Digoxin has been widely used to treat certain heart conditions such as heart failure and cardiac arrhythmias. It works by improving the efficiency of the heart muscle and regulating the heart rate. It is now rarely used for the treatment of these conditions. One of the reasons for this was the difficulty in dosing the drug. For some people, even the smallest amounts of digoxin worked, while others needed a much higher dose. One possible explanation is probably hidden in our intestines.

How the microbiome influences drugs

Certain strains of E. lenta are able to metabolize and inactivate digoxin, which reduces the effectiveness of the drug in the body. This microbial metabolism is carried out by the enzyme cardiac glycoside reductase, which converts digoxin into a less active form. And here another factor comes into play to make the whole context more complex. Colleen Cutcliffe, a molecular biologist, said in Peter Attia's podcast that it makes a difference whether E. lenta has one copy of the gene that codes for the enzyme or five genes. People who have an E. lenta form with five genes for inactivating digoxin seem to respond much less well to the drug. If we can find out more about these interactions in the future, this will be a further step towards personalized medicine.

How can you strengthen the microbiome?

Now that we have learned a lot about testing and the background to the microbiome, let's look at what we can do to build up or strengthen the microbiome.

Before we dive deeper into the topic, we need to define a few terms: If you want to know more about the individual topics, you can simply click on the word and you will be taken to a detailed article:

• Probiotics: These are preparations that contain live intestinal bacteria, for example. Probiotics are often used to make the intestinal flora more diverse again, or to restore the balance between "good" and "bad" bacteria
• Prebiotics: Prebiotics are substances, usually indigestible carbohydrates such as inulin, fructooligosaccharides (FOS) and galactooligosaccharides (GOS), which selectively promote the activity or growth of health-promoting microorganisms in the gut. You can find them in food as dietary fiber and they serve as "food" for your intestinal bacteria

Did you know?

The German Nutrition Society (DGE) recommends a daily intake of at least 30 grams of fiber for adults. These substances are found exclusively in plant products, e.g. wholemeal products, fruit and vegetables. A high fiber content in the diet ensures that the bacteria in the intestines get enough food. However, most people eat less than the recommended 30 grams per day.

• Symbiotics: Symbiotics are products or food supplements that contain a combination of probiotics and prebiotics. The idea behind this is that the prebiotics serve as a source of nutrients for the living microorganisms supplied with the probiotics, which can improve their survival, colonization and effectiveness in the intestinal tract.
• Postbiotics: Postbiotics are bioactive compounds produced by the metabolic activity of probiotic microorganisms in the gut. These include short-chain fatty acids (such as butyrate, propionate and acetate), bacteriocins, enzymes, vitamins and other metabolites. These substances can have positive effects on the host, for example by supporting the intestinal barrier function, having an anti-inflammatory effect and modulating the immune system.

You can strengthen your intestinal flora in all these ways. The easiest way is probably to adjust your diet by eating more fiber. If you are not currently eating a lot of fiber per day, it is best to increase the amount slowly, otherwise you may experience bloating or gastrointestinal problems. You can find out more about this topic in our article on building intestinal flora.

Butyrate metabolism - not only important for intestinal health

Butyrate metabolism refers to the biochemical process by which certain microorganisms in the human gut ferment indigestible carbohydrates (especially fiber), producing short-chain fatty acids (SCFAs) such as butyrate. Butyrate is of particular interest as it has multiple beneficial effects on our health, including promoting gut health, strengthening the gut barrier function, anti-inflammatory effects and potential protective mechanisms against metabolic diseases such as type 2 diabetes mellitus.

Butyrate production in the intestine

Butyrate production occurs through the fermentation of dietary fiber by anaerobic bacteria in the large intestine. These bacteria, which include genera such as Faecalibacterium, Eubacterium, Roseburia and Butyrivibrio, use fiber as an energy source and produce SCFAs, including butyrate. Butyrate then serves as the main source of energy for the cells of the intestinal mucosa (colonocytes) and supports their health and function. Incidentally, the intestinal mucosa cells are the only cells in the body that can use butyrate as an energy source.

Did you know?

You may be familiar with the "miracle weight loss drug" Ozempic, also known as a weight loss injection. It is actually a medication for diabetes mellitus that mimics a hormone in the body. To be precise, GLP-1 (glucagon-like peptide-1). You can find out more about this in the article about berberine. But back to the microbiome. The butyrate produced by the bacteria can stimulate the L-cells in the gut, which in turn produce the hormone GLP-1. Therefore, a diet rich in fiber can indirectly increase GLP-1 secretion by stimulating butyrate production and thus have positive effects on glucose metabolism and appetite regulation.

The role of Bacillus subtilis

Bacillus subtilis, often cited as a probiotic bacterium, plays a slightly different role in the microbiome than the direct producers of butyrate. B. subtilis is a Gram-positive, soil-living bacterium that can also be found in the human gut. It is known for its ability to form robust endospores that enable it to survive difficult environmental conditions. Although B. subtilis is not directly involved in the production of butyrate, it can still have indirect effects on butyrate metabolism and overall gut health:

• Promoting healthy gut flora: B. subtilis can support the growth and activity of butyrate-producing bacteria in the gut by promoting microbial diversity and ecological balance.
• Stimulation of the immune system: B. subtilis can modulate the immune response and contribute to the integrity of the intestinal barrier, which can indirectly improve the environment for butyrate production.
• Competition with pathogenic microorganisms: Due to its antimicrobial properties, B. subtilis can inhibit the growth of harmful bacteria, thus supporting a healthier intestinal flora, which in turn promotes butyrate production.

All these properties contributed to B. subtilis being named Microbe of the Year in 2023.

The microbiome and its role in longevity

The older we get, the more our microbiome loses diversity. In the worst case, a symbiosis becomes a dysbiosis. The changes in the microbiome can be so serious that they have been included as one of the Hallmarks of Aging. These describe the molecular changes that come with age. The hope is that if we can reverse these hallmarks, we can also stop ageing.

Conclusion

"...a diseased intestine is the root of all evil...", Hippocrates already knew. An intact gut is extremely important for our health and a long life. Understanding the molecular composition of the intestinal flora is a challenge that we must now meet. Our microbiome is a highly complex and exciting field of research. Thanks to the newer methods of genetic analysis and proteomics, we have come a step closer to better understanding our intestinal flora. In the future, personalized medicine could also go hand in hand with the microbiome.