Abstract
Huge numbers of bacteria live in the human gut. We know those bacteria are important to our health, so we need to treat them well. We wanted to know whether it was possible to design new yogurts that can introduce special bacteria into the gut, to improve our well-being. We studied hundreds of types of bacteria isolated from cheese and yogurt and found that 24 of these bacterial species can perform most of the important bacterial functions that happen in the human gut. Therefore, there is exciting potential for designing new, gut-healthy yogurts.
Bacteria Keep us Healthy
Bacteria were among the first life forms to appear on Earth. They are extremely small organisms, consisting of a single cell. There are many species (major types) of bacteria that can be incredibly different from each other: some prosper deep below the ocean, at temperatures higher than that of boiling water, while others live happily in Antarctic ice. Bacteria populate the entire surface of Earth. So, it is not surprising that some bacterial species live with humans—a vast number of bacteria live in and on our bodies. Unfortunately, humans commonly think of bacteria as bad, because some types of bacteria can make us sick. Yes, there are bad guys—but there are also good guys! In fact, most bacterial species do not make us sick, and some even help us stay healthy [1, 2]. Most of the bacteria that live inside humans are found in the gut. These good bacteria protect us against disease-causing bacteria, help us digest food, and produce vitamins that our bodies need but cannot produce on their own [1]. Recently, researchers found that gut bacteria can even influence mental health [1]. Together, this collection of gut bacteria is known as the gut microbiome.
What Makes a Healthy Gut Microbiome?
How can we nurture good gut bacteria without strengthening the bad ones? One way is to feed our good gut bacteria their favorite foods. Fast foods, for example, even though they are very tasty, are good neither for us nor for our gut bacteria. Fast foods are full of sugar and low in vitamins and fiber. Most good gut bacteria prefer to be fed fiber, and if there is not enough, they can starve! It is important for the gut microbiome to contain many different types of bacteria, because a high diversity in the gut microbiome makes us more resistant to infections and to the effects of the occasional fast-food treat. Why might that be?
Suppose the bacteria in the gut are very diverse. Some like to eat sugar, some fat, some fiber, and some protein. In that case, when there is no sugar around, only the sugar-eating bacteria become weak—the others are fine, which means that, as a whole, the community is still strong. However, if most bacteria only ate sugar, the microbiome would become weak in the absence of sugar, making it much easier for bad bacteria to conquer the gut and cause illness. This is one reason why a balanced diet is important.
There is another reason why a lack of diversity in the gut microbiome may be bad. When gut bacteria are diverse, multiple types of bacteria can perform the same job in the bacterial community, like digesting milk sugar or vitamin production. If one species of bacteria is lost, another might be able to take its place. In a less diverse gut microbiome, this might not be possible, and the gut microbiome may be weakened. One strategy for strengthening the gut microbiome, and thus human health, could be ensuring that there are several different bacterial species that can perform the same functions. We can achieve this by supplementing those bacteria through our diets.
Can Yogurt or Cheese Support the Gut Microbiome?
Bacteria can be found in many foods, particularly in dairy products like cheese or yogurt, which have been consumed for ages. Ten thousand years ago, when most people still lived as hunter-gatherers, all humans were lactose intolerant, which means they could drink milk when they were young, but if they did so as adults, they would feel bloated and sick. When humans started farming sheep, cows, and other milk-producing animals, they discovered ways to process milk so that it tasted different, lasted longer, and, most importantly, could be digested without making them feel sick [3]. We call this process fermentation, and it led to the production of the first yogurts and cheeses. What these early communities did not know was that bacteria were responsible for fermentation. Specific species of bacteria live and grow in milk, changing its taste, texture, and composition. After fermentation, a cup of yogurt (200 g) contains more bacteria (at least 20 billion) than there are humans on Earth (8 billion)!
Early yogurts contained many distinct species of bacteria, and every yogurt was different. In contrast, most modern yogurts only contain two species of bacteria, selected for fast and reliable mass production. Could we make yogurt from a different cocktail of bacteria, optimized not just for mass production but also to help the gut microbiome and improve human health (Figure 1)?
The Quest for the Right Bacteria
Where could we get suitable bacteria for making gut-healthy yogurt? Switzerland has a proud tradition of cheese and yogurt making. Agroscope, the Swiss center of excellence for agricultural research, collects, stores, and investigates the bacteria found in yogurt and cheese. So far, Agroscope has collected over 10,000 different bacteria from dozens of species!
With such a large bacterial bank, how do we decide which are the best for a healthy yogurt? Conveniently, scientists at Agroscope have studied the DNA of close to 1,000 of the bacteria they have collected, using a process called sequencing, to see which genes the bacteria have. Genes are short segments of DNA that code for functions that allow bacteria to survive. For example, certain genes enable bacteria to split into two, and others give them the ability to swim around.
Supplementing the Gut Microbiome
Our idea was to see if yogurt bacteria could support gut bacteria in their work, and possibly even increase the diversity of the gut microbiome. We used DNA sequences from four human microbiomes, which contained a mix of genes from many different gut bacteria. Then, we used a computer program to determine the functions of these genes, using the same method we used for the dairy bacteria (Figure 2).
When we compared the dairy bacteria to bacteria from the human microbiome, we were surprised: each individual bacterial species from the milk could perform about half of the functions of the human gut microbiome, even though dairy bacteria are from a completely different environment and are rarely found in the human gut. Combined, our 24 species of dairy bacteria covered 89% of the functions of the human gut microbiome [4]! We also noticed that some human microbiomes lack certain functions compared to other human microbiomes. Some of those functions are present in dairy bacteria, meaning we may be able to develop a yogurt that can supplement missing or lost functions in a human microbiome, making it more resilient and thus helping people to be healthier.
What Is Next?
Our study shows that bacteria from cheese or yogurt have similar functions to those of human gut bacteria. We think this knowledge will be very useful. For example, people with certain diseases, like obesity, lack specific types of gut bacteria. So, in future studies, we could recruit study participants with a known disease who lack the gut bacteria that perform certain functions. Then we could search Agroscope’s collection for milk bacteria that have the missing functions and produce a special yogurt with them. Next, we could feed this yogurt to the participants and evaluate the effects on their health.
Humans have been raising cattle and eating fermented foods for millennia, but only recently have we gained the understanding and the tools to develop health-promoting dairy foods based on scientific data. This process is long, but worthwhile! If scientists continue to explore the potential of bacteria to improve human health, we may eventually be able to help many people with diseases like obesity and diabetes by feeding those people foods that contain helpful bacteria.
Funding
This research was funded by Gebert Rüf Stiftung within the program Microbials, Grant No. GRS-070/17.
Glossary
Species: ↑ A group of organisms, like bacteria, that behave similarly and have very similar genomes.
Gut Microbiome: ↑ All the bacteria that live in the human gut.
Diversity: ↑ The variety of living things in a particular habitat. The more species, the higher the diversity.
Fermentation: ↑ The production of foods such as yogurt, cheese, bread, kimchi, beer, and wine with the help of yeast or bacteria.
Sequencing: ↑ The process of studying the DNA composition of an organism.
Gene: ↑ A segment of DNA that determines a specific characteristic, capability, or function of a life form.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
[1] ↑ Wang, H., Wei, C. X., Min, L., and Zhu, L. Y. 2018. Good or bad: gut bacteria in human health and diseases. Biotechnol. Biotechnol. Equipment. 32:1075–80. doi: 10.1080/13102818.2018.1481350
[2] ↑ Marco, M. L., Sanders, M. E., Gänzle, M., Arrieta, M. C., Cotter, P. D., de Vuyst, L., et al. 2021. The international scientific association for probiotics and prebiotics (ISAPP) consensus statement on fermented foods. Nat. Rev. Gastroenterol. Hepatol. 18:96–208. doi: 10.1038/s41575-020-00390-5
[3] ↑ Curry, A. 2013. The milk revolution. Nature 500:20–2. doi: 10.1038/500020a
[4] ↑ Roder, T., Wüthrich, D., Bär, C., Sattari, Z., von Ah, U., Ronchi, F., et al. 2020. In silico comparison shows that the pan-genome of a dairy-related bacterial culture collection covers most reactions annotated to human microbiomes. Microorganisms. 8:966. doi: 10.3390/microorganisms8070966