How is my gut actually doing? This question is more relevant than ever, as we are becoming increasingly aware of our gut microbiome, which is now held responsible for many of our body's mechanisms. Many factors, over which we probably have more influence than previously assumed, determine whether we live to a ripe old age. The latest research indicates that our gut flora plays a key role in how long we live and which diseases we will fall ill with.
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 get started, 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 z.B. the gastrointestinal tract (especially the gut), the skin, the mouth, the respiratory tract and the urogenital system.
In this article, we will mainly focus on the gut 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 gut 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 most likely not be able to survive. The microbiome is z.B. essential for the assimilation of certain nutrients from food. The human body alone does not have the full range of enzymes needed to break down every nutrient.
Waste products and the gut feeling
The term microbiome is used synonymously with gut flora and refers to the entirety of microorganisms that colonize our gut. What the human organism often regards as "waste", such as fiber, serves the intestinal flora as an essential source of nutrition. 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.
In addition, there is a significant connection between the microbiome and the enteric nervous system -an extensive network of neurons that permeates 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 to play a role in insulin resistance, a precursor of 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 microbiome research is still relatively 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. To get around this problem, the researchers have come up with various possibilities. One of them 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 exploring 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 goal 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. 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
- Influence on 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
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 9000 people in an age group of 18 to 101 years was compared with each other. The researchers found that it is not only people themselves who age, but also the microbiome of the gut. 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 usedfor 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 workload. 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 a little. This allows researchers to distinguish between different bacterial species.
Did you know
A brief explanation of the term. Bacteria are divided into families and strains. The first part of the word represents the family name, z.B. 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.
More microbiome tests
In addition to those already mentioned, there are several other tests. Commonly used are shotgun metagenome sequencing and metaproteomics. The former offers the advantage over 16S rRNA gene sequencing that other organisms, such as viruses or fungi, are also included. Metaproteomics does not look at genetics, but at the proteinsthat are 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 epigenetics, where the markers on the DNA are measured, proteomics looks at the proteins produced. This is also the basis of the latest test from MoleQlar, which allows you to find out your molecular profile. In collaboration with the renowned LMU Munich, we offer you a deeper insight into your molecular self.
Discover your proteome with the Molecular Profile test from MoleQlar. Learn more now.
It's not just the genes
The field of research into 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 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 gut.
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 occurs through 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 a E.lenta form with five genes for the inactivation of digoxin appear to respond significantly less well to the drug. If we can find out more about these interactions in the future, this will be another step towards personalized medicine.
How to 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 z.B. live intestinal bacteria. Probiotics are often used to make the intestinal flora more species-rich again, or to restore the balance between "good" and "bad" bacteria
- Prebiotics: Prebiotics are substances, mostly 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 fiberfor adults. These substances are found exclusively in plant products, z.Bwholemeal products, fruit and vegetables. A high fiber content in the diet ensures that the bacteria in the intestine 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 live 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 to include more fiber. If you are not currently consuming 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 up intestinal flora.
The butyrate metabolism - not only important for gut health
Butyrate metabolism refers to the biochemical process by which certain microorganisms in the human gut ferment indigestible carbohydrates (especially dietary fiber) and produce 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 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, producing 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. This is actually a medication for diabetes mellitus that mimics a hormone in the body. To be precise, the GLP-1 (glucagon-like peptide-1). You can find out more about this in the article on Berberin. 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. Thus, 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.
Bioavailable berberine with chromium and zinc in the mineral complex Berbersome
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 allow it to survive difficult environmental conditions. Although B. subtilis is not directly involved in the production of butyrate, it may 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: Through its antimicrobial properties, B. subtilis can inhibit the growth of harmful bacteria, 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 severe 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.
Fazit
"...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 latest methods of genetic analysis and proteomics, we have come one step closer to better understanding our gut flora. In the future, personalized medicine could also go hand in hand with the microbiome.
