December 20, 2024

The 2,500-Year-Old Gut Remedy That Science Just Rediscovered

For thousands of years, various cultures have used medicinal clays. The earliest recorded use dates back to Mesopotamian clay tablets from around 2500 BC. The Egyptians and several Indigenous cultures also utilized these clays — and some still do today. On the Greek island of Crete and nearby regions, a specific clay known as Lemnian Earth was particularly valued. Now, researchers have explored Lemnian Earth’s properties and discovered that combining natural clay with a therapeutic fungus can beneficially reshape the gut microbiome.

Lemnian earth clay tablets and view of city
Left: Collection of Lemnian earths (sphragides) from the collection of Basel University Museum of Pharmacy. Right: View of Lemnos Island. Image credits: Glasgow University / Wikipedia.

For millennia, Lemnian Earth (also known as terra sigillata) was used to treat digestive problems. Sourced from the volcanic island of Lemnos in the North Aegean, this clay was traditionally blessed by priests and stamped with an official seal to guarantee authenticity. It was prescribed for ailments ranging from gastrointestinal issues to poisoning and even plague prevention.

Researchers from Crete and Scotland had a theory that Lemnian Earth may not be a natural material but an artificially modified one involving a clay-fungus interaction.

The exact recipe for Lemnian Earth is unknown. Despite its long history and several historical accounts of its preparation, the precise method and ingredients used to create this therapeutic clay are not fully known. Ancient texts describe rituals involving the extraction of clay from specific sites on Lemnos, washing, purification processes, and blessings by priests. Scientists from the University of Glasgow, University of Strathclyde, and the Technical University of Crete tried to recreate it.

DIY Lemnian Earth

They used two types of clay — smectite and kaolin — and a fungus called Penicillium purpurogenum. The researchers hypothesized that the therapeutic benefits arose not from the clay alone but from its interaction with the fungus. To test this, they cultured the fungus with each type of clay and analyzed the resulting leachates (liquid extracts).

“Our study began many years ago on the island of Lemnos in the northern Aegean, Greece. By examining historical samples (16th-18th Common Era) from Basel University’s Museum of Pharmacy we found that these samples contained specific types of fungi which were not present in the natural Lemnos clay,” says Effie Photos-Jones, an archaeological scientist from the School of Humanities at the University of Glasgow, lead investigator of the study.

“This led us to wonder if they were part of the original recipe. Ancient texts mention a ‘blessing’ ritual involving wheat and barley, suggesting that these grains — often infected during storage with certain fungi — might have been intentionally added. Speculating on this led, to our knowledge, the first ever attempt to establish the presence and nature of microorganisms (bacteria, fungi) within ancient mineral therapeutics (DNA sequencing), following an approach developed by Dr Charles Knapp at Strathclyde University.”

The folk remedy seems to work

The results were striking. Only the combination of Penicillium purpurogenum with smectite clay produced a mixture with significant antibacterial properties. This mixture inhibited the growth of both Gram-positive and Gram-negative bacteria, including Escherichia coli and Staphylococcus aureus in a lab. The kaolin mixture, by contrast, showed little antibacterial activity.

“The results were very interesting. Testing against common pathogens showed that the combination of smectite clay and fungus had considerably better antibacterial activity compared to other clays and the control,” says Professor Danae Venieri from the Technical University of Crete.

The team took their research a step further, feeding the mixture to mice and observing the effects on their gut microbiomes. The results were encouraging: mice that received the Penicillium purpurogenum-smectite leachate showed increased microbial diversity in their guts. In contrast, mice given the kaolin-based leachate did not experience the same benefits.

Microbial diversity is important. Low diversity, or dysbiosis, has been linked to various inflammatory conditions, including Crohn’s disease and ulcerative colitis. Essentially, the clay-fungus mixture seemed to promote a healthier gut environment.

Why does the clay work?

The team used a technique called liquid chromatography-mass spectrometry (LC-MS) to establish the bioactive compounds within. They found several bioactive compounds, some common to several types of clay, some unique to this smectite.

“Clays which include iron and titanium compounds have been known to interact with microorganisms (bacteria) but the role the clay minerals, themselves, which are the main constituents of clays, has not been previously considered important,” says George Ε Christidis, from the University of Crete.

The researchers also found that the smectite-based leachate increased the production of short-chain fatty acids (SCFAs) in the mice’s guts. SCFAs, such as acetate, propionate, and butyrate, are important for gut health. They are produced by gut bacteria during the fermentation of dietary fiber and play a key role in maintaining intestinal and systemic health.

Can we turn this into a pill?

The findings have far-reaching implications. While probiotics and prebiotics are common ways to promote gut health, they have limitations. Probiotics can struggle to survive the harsh conditions of the gastrointestinal tract, and prebiotics can have unpredictable outcomes due to the complexity of the gut microbiome.

The clay-fungus leachate offers a potential new approach: a non-dietary, small-molecule intervention that modulates the gut microbiome. This could pave the way for new treatments for inflammatory diseases, gut infections, and even metabolic disorders.

The research also supports a connection to historical and folk remedies, which would make these clay tablets more palatable to a larger part of people in society.

It’s still early days and the effectiveness hasn’t yet been demonstrated in humans. However, the prospects are encouraging. Lemnian Earth, once a forgotten relic, could inspire new therapies in the 21st century.

The study was published in PLoS.