"The gut microbiota not only contributes to the functioning of the gastrointestinal tract but may also influence metabolism throughout the body. Mulberry is particularly interesting in this respect because it contains numerous bioactive compounds, including polyphenols and polysaccharides, which may interact with gut microorganisms," explains Anna Prescha, PhD, DSc, Professor at Wroclaw Medical University, from the Department of Dietetics and Bromatology.

Different Mulberries Contain Different Compounds

Research to date has concentrated mostly on white mulberry (Morus alba), although black mulberry (Morus nigra), especially its fruit, has also produced notable results.

Mulberry leaves contain several biologically active substances, including 1-deoxynojirimycin (DNJ), which is known to affect carbohydrate metabolism, along with polyphenols and polysaccharides. Black mulberry fruit, meanwhile, contains high levels of anthocyanins and other phenolic compounds, as well as polysaccharides.

How the plant material is processed can also make a major difference. Drying, fermentation, and extraction methods can change both the amount and relative proportions of bioactive compounds. As a result, two preparations made from the same plant material may differ considerably in composition and biological effects.

Mulberry May Alter Gut Bacteria

The review found that preparations made from both mulberry leaves and fruit may affect the composition and activity of the gut microbiota. Some studies reported shifts in beneficial bacteria along with higher production of short-chain fatty acids such as acetate, propionate, and butyrate.

These compounds are produced when gut microbes ferment dietary material and are important for normal intestinal function. In some experiments, changes in the microbiota were also associated with improvements in measurements related to glucose and lipid metabolism.

The results, however, were not consistent across every preparation. Both the material being studied and the way it was processed appeared to influence the outcome.

Black mulberry fruit polysaccharides offer one example. Researchers using different extraction techniques produced fractions with different structures and different levels of utilization by gut microbes. Fractions produced through water extraction and with pectate lyase showed the strongest prebiotic potential.

Studies involving polysaccharides from mulberry leaves also suggest that structural characteristics matter. Features such as molecular weight and monosaccharide composition may determine which bacteria can use the compounds as a substrate and which short-chain fatty acids are ultimately produced.

Combined Mulberry Compounds Show Stronger Effects in Mice

Some of the most intriguing findings came from experiments involving more complex mulberry preparations.

In mice fed a high-fat diet, a fraction containing both polyphenols and polysaccharides from white mulberry fruit produced more favorable changes in the gut microbiota than either fraction given on its own. Those microbial changes were accompanied by improvements in some measures linked to metabolic syndrome and intestinal health.

Researchers also performed a microbiota transplantation experiment using the same model. Gut microbiota from mice that had received the combined mulberry fraction were transferred to other animals. Those recipients also showed improvements in some metabolic disturbances, adding evidence that changes in the microbiota may help drive the effects of the mulberry preparation.

"These findings suggest that what matters is not only the presence of an individual compound, but also the complex composition of the preparation, the proportions of its compounds, and their interactions. Therefore, rather than searching for a single universal product, it is worth determining which combination of species, plant part, composition, and processing method produces a specific biological effect," emphasizes Prof. Anna Prescha.

The Research Began With a Student Idea

The project grew out of the Nutri-Sfera Student Research Group at the Department of Dietetics and Bromatology at Wroclaw Medical University.

The topic was proposed by two students who have since graduated: Marta Miszczak from the Dietetics program and Karolina Kłosowska-Buryło from the Pharmacy program. Their involvement brought together nutritional and pharmaceutical approaches to studying mulberry and the gut microbiota.

"This fitted very well with the interdisciplinary nature of the study. It combined a perspective on mulberry as a plant material with a specific composition with an analysis of its potential effects on the microbiota and metabolism," adds Prof. Prescha.

Human Studies Are Still Missing

Despite the promising experimental findings, one major question remains unresolved. Researchers have not yet conducted human studies that directly examine how mulberry preparations affect the gut microbiota.

Most of the existing evidence comes from animal models and in vitro experiments. Comparing results across studies is also difficult because relatively few investigations combine biological findings with a detailed chemical analysis of the exact mulberry preparation being tested.

"The available findings are promising, but at this stage they do not allow us to determine whether the relationships observed in experimental models between mulberry preparations, the microbiota, and metabolism also occur in humans," Prof. Prescha points out.

Researchers say clinical trials will need to use carefully characterized and standardized mulberry preparations. Such studies could help determine how different products affect the human gut microbiota, how large those effects are, and whether they result in measurable health benefits.

Did You Know?

Mulberry leaves and fruit contain different compounds. The leaves contain, among other substances, DNJ, which is associated with carbohydrate metabolism, while black mulberry fruit is particularly rich in anthocyanins.

Processing can change mulberry's biological effects. Even preparations made from the same plant part may behave differently depending on the extraction or fermentation method.

In experimental studies, combining compounds sometimes produced stronger effects than using them separately. In mice, a combination of polyphenols and polysaccharides from white mulberry fruit produced greater beneficial changes in the microbiota than either fraction alone.

The gut microbiota may also help mediate these effects. In one experiment, transferring microbiota from mice that received a mulberry preparation to other animals was associated with improvements in some metabolic disturbances.

The biggest unanswered question is whether these findings apply to people. No human studies have yet directly tested how mulberry preparations affect the gut microbiota.