“One Grain to Bind Them All”

/ / Health, Science

A new study on kefir found that the individual dominant species of Lactobacillus bacteria in kefir grains cannot survive in milk on their own. The bacteria need one another to create the fermented dairy drink, “feeding on each other’s metabolites in the kefir culture.”

The research, conducted by EMBL (Europe’s laboratory for life and sciences) and Cambridge University’s Patil group and published in Nature Microbiology, illustrates a dynamic of microbes that had eluded scientists. Though scientists knew microorganisms live in communities and depend on each other to survive, “mechanistic knowledge of this phenomenon has been quite limited,” according to a press release on the research.

“Cooperation allows them to do something they couldn’t do alone,” says Kiran Patil, group leader and author of the paper. “It is particularly fascinating how L. kefiranofaciens, which dominates the kefir community, uses kefir grains to bind together all other microbes that it needs to survive — much like the ruling ring of the Lord of the Rings. One grain to bind them all.”

To make kefir, it takes a team. A team of microbes.

The group studied 15 samples of kefir, one of the world’s oldest fermented food products. Below are highlights from a press release on the published results. 

A Model of Microbial Interaction

Kefir first  became popular centuries ago in Eastern Europe, Israel, and areas in and around Russia. It is composed of ‘grains’ that look like small pieces of cauliflower and have fermented in milk to produce a probiotic drink composed of bacteria and yeasts.

People were storing milk in sheepskins and noticed these grains that emerged kept their milk from spoiling, so they could store it longer,” says Sonja Blasche, a postdoc in the Patil group and an author of the paper. Because milk spoils fairly easily, finding a way to store it longer was of huge value.”

To make kefir, you need kefir grains, which must come from another batch of kefir. They cannot be made artificially. The grains are added to milk, to ferment and grow. Approximately 24 to 48 hours later (or, in the case of this research, 90 hours later), the kefir grains have consumed the available nutrients. The grains have grown in size and number, and are removed and added to fresh milk — to begin the process anew.

For scientists,  kefir is more than just a healthy beverage: it’s an easy-to-culture model microbial community for studying metabolic interactions. And while kefir is quite similar to yogurt in many ways – both are fermented or cultured dairy products full of ‘probiotics’ – kefir’s microbial community is far larger, including not just bacterial cultures but also yeast.

A “Goldilocks Zone”

While scientists know that microorganisms often live in communities and depend on their fellow community members for survival, mechanistic knowledge of this phenomenon has been quite limited. Laboratory models historically have been limited to two or three microbial species, so kefir offers – as Patil describes – a ‘Goldilocks zone’ of complexity that is not too small (around 40 species), yet not too unwieldy to study in detail.

Blasche started this research by gathering kefir samples from several sources. Though most  were obtained in Germany, they may have  originated elsewhere, grown from kefir grains  passed down through the years..

“Our first step was to look at how the samples grow. Kefir microbial communities have many member species with individual growth patterns that adapt to their current environment. This means fast- and slow-growing species and some that alter their speed according to nutrient availability, Blasche  says. This is not unique to the kefir community. However, the kefir community had a lot of lead time for coevolution to bring it to perfection, as they have stuck together for a long time already.”

Cooperation is key

Finding out the extent and nature of  cooperation among kefir microbes was far from straightforward. Researchers combined a variety of state-of-the-art methods, such as metabolomics (studying metabolites’ chemical processes), transcriptomics (studying the genome-produced RNA transcripts) and mathematical modelling. These processes  revealed not only key molecular interaction agents like amino acids, but also the contrasting species dynamics between  grains and  milk.

“The kefir grain acts as a base camp for the kefir community, from which community members colonise the milk in a complex yet organised and cooperative manner,” Patil says. “We see this phenomenon in kefir, and then we see it’s not limited to kefir. If you look at the whole world of microbiomes, cooperation is also a key to their structure and function.”

In fact, in another paper from Patil’s group (in collaboration with EMBL’s Bork group) in Nature Ecology and Evolution, scientists combined data from thousands of microbial communities across the globe – from in soil to in the human gut – to understand similar cooperative relationships. In this second paper, the researchers used advanced metabolic modelling to show that the co-occurring groups of bacteria, groups that are frequently found together in different habitats, are either highly competitive or highly cooperative. This stark polarization hadn’t been observed before, and sheds light on evolutionary processes that shape microbial ecosystems. While both competitive and cooperative communities are prevalent, the cooperators seem to be more successful in terms of higher abundance and occupying diverse habitats — stronger together!