Tuesday, December 16, 2025

New biomolecular technique reveals species specific plant consumption in human dental calculus of medieval Ukraine

Vilnius University

Miliacin Biomolecule in Human Dental Calculus from the Ostriv Burial — image:
The image shows a representation of the miliacin biomolecule embedded within the dental calculus of human teeth from the Ostriv burial. The molecule is specific to the broomcorn millet plant and is incorporated into the calculus matrices during the consumption of millet-based meals.
view more
Credit: Dr. Aleksandra Kozak

Detecting What Isotopes Miss

“Our findings demonstrate that even the smallest traces of millet leave molecular fingerprints in dental calculus,” said Dr Shinya Shoda, co-lead author from the Nara National Research Institute for Cultural Properties. “This opens up an entirely new way to detect subtle dietary practices in the past.”

Traditional stable isotope analysis can identify millet consumption only when it makes up more than ~20% of an individual’s dietary protein. As a result, low-level or occasional millet consumption, especially common in seasonal, opportunistic, or socially variable diets, often goes unnoticed. In this study, several individuals with clear miliacin signals showed depleted δ¹³C values, suggesting that conventional isotopic analyses would have overlooked their intake of C4 plants such as millet. In other words, the conventional isotopic approach would have suggested that these people did not eat millet at all – while the molecular evidence clearly shows they did. This highlights how easily such subtle dietary signals can be missed by traditional methods.

A New Tool for Reconstructing Ancient Diets

The successful use of TD-GC/MS on microgram-scale samples – far smaller than previously possible – marks a significant methodological advance. The approach is efficient, minimally destructive, and broadly applicable across archaeological contexts.

“This technique allows us to access underrepresented plant foods that rarely appear in the archaeological record,” said Prof. Giedrė Motuzaitė Matuzevičiūtė, co-lead author. “It gives us a clearer picture of everyday diets and how people adapted to local environments and cultural changes.”

Insights into Medieval Communities

The medieval population of Ostriv, part of the Kievan Rus’ cultural sphere and influenced by both Slavic and Baltic communities, showed variable dietary histories. In several individuals, miliacin was found despite isotope signatures reflecting little childhood exposure to millet: suggesting adoption of millet consumption later in life, possibly linked to migration or changing food availability.

“Dental calculus is a biological material often found on human teeth. Finding species-specific plants in the calculus matrix in combination with other biomolecular archaeology techniques” opens a new possibility to understand the nutrition of past populations,” says the anthropologist of the study, Dr Aleksandra Kozak from the Institute of Archaeology in Kyiv.

This study highlights the transformative potential of dental calculus analysis for identifying ancient plant use. The new methodology may reshape our understanding of dietary diversity across time, geography, and social identities. This research will also be vital in understanding processes of dietary shifts to new crop consumption in various societies before they become ubiquitous. “This study also holds immense potential for identifying biomolecules of other underrepresented plants of economic and medicinal importance”, said Prof. G. Motuzaitė Matuzevičiūtė.

This research was supported by the European Research Council Consolidator Grant “MILWAYS – Past and Future Millet Foodways” (101087964), awarded to Prof. Motuzaitė Matuzevičiūtė at Vilnius University, the Mitsubishi Foundation Research Grants in the Humanities awarded to Dr Shoda (SOUP, 202420018) and the “Baltic migrants at the border of the Kievan Rus” German Science Foundation (DFG) project P508078428 represented by Dr Kozak’s contribution.

Journal

Scientific Reports

Article Title

Thermal desorption GC/MS on human dental calculus detected minute millet consumption in medieval Ukraine

Article Publication Date

9-Dec-2025

Gut bacteria from amphibians and reptiles achieve complete tumor elimination

Peer-Reviewed Publication

Japan Advanced Institute of Science and Technology

Figure 1. Anticancer efficacy and Tumor response. — image:
Anticancer efficacy: *Ewingella americana* versus conventional therapies. Tumor response: single i.v. dose of *E. americana* (200 µL, 5 × 10⁹ CFU/mL); four doses of doxorubicin or anti–PD-L1 (200 µL, 2.5 mg/kg per dose); PBS as control. Data: mean ± SEM (n = 5). ****, p < 0.0001 (Student’s two-sided t-test).
view more
Credit: Eijiro Miyako from JAIST.

【Key Research Achievements】

Demonstration that natural bacteria isolated from amphibian and reptile intestines achieve complete tumor elimination with single administration
Combines direct bacterial killing of cancer cells with immune system activation for comprehensive tumor destruction
Outperforms existing chemotherapy and immunotherapy with no adverse effects on normal tissues
Expected applications across diverse solid tumor types, opening new avenues for cancer treatment

【Research Overview】

A research team of Prof. Eijiro Miyako at the Japan Advanced Institute of Science and Technology (JAIST) has discovered that the bacterium Ewingella americana, isolated from the intestines of Japanese tree frogs (Dryophytes japonicus), possesses remarkably potent anticancer activity. This groundbreaking research has been published in the international journal Gut Microbes.

While the relationship between gut microbiota and cancer has attracted considerable attention in recent years, most approaches have focused on indirect methods such as microbiome modulation or fecal microbiota transplantation. In contrast, this study takes a completely different approach: isolating, culturing, and directly administering individual bacterial strains intravenously to attack tumors—representing an innovative therapeutic strategy.

The research team isolated a total of 45 bacterial strains from the intestines of Japanese tree frogs, Japanese fire belly newts (Cynops pyrrhogaster), and Japanese grass lizards (Takydromus tachydromoides). Through systematic screening, nine strains demonstrated antitumor effects, with E. americana exhibiting the most exceptional therapeutic efficacy.

【Research Details】

Remarkable Therapeutic Efficacy

In a mouse colorectal cancer model, a single intravenous administration of E. americana achieved complete tumor elimination with a 100% complete response (CR) rate. This dramatically surpasses the therapeutic efficacy of current standard treatments, including immune checkpoint inhibitors (anti-PD-L1 antibody) and liposomal doxorubicin (chemotherapy agent) (Figure 1).

Dual-Action Anticancer Mechanism

E. americana attacks cancer through two complementary mechanisms (Figure 2):

Direct Cytotoxic Effect: As a facultative anaerobic bacterium, E. americana selectively accumulates in the hypoxic tumor microenvironment and directly destroys cancer cells. Bacterial counts within tumors increase approximately 3,000-fold within 24 hours post-administration, efficiently attacking tumor tissue.
Immune Activation Effect: The bacterial presence powerfully stimulates the immune system, recruiting T cells, B cells, and neutrophils to the tumor site. Pro-inflammatory cytokines (TNF-α, IFN-γ) produced by these immune cells further amplify immune responses and induce cancer cell apoptosis.

Tumor-Specific Accumulation Mechanism

E. americana selectively accumulates in tumor tissues with zero colonization in normal organs. This remarkable tumor specificity arises from multiple synergistic mechanisms:

Hypoxic Environment: The characteristic hypoxia of tumor tissues promotes anaerobic bacterial proliferation
Immunosuppressive Environment: CD47 protein expressed by cancer cells creates local immunosuppression, forming a permissive niche for bacterial survival
Abnormal Vascular Structure: Tumor vessels are leaky, facilitating bacterial extravasation
Metabolic Abnormalities: Tumor-specific metabolites support selective bacterial growth

Excellent Safety Profile

Comprehensive safety evaluation revealed that E. americana demonstrates:

Rapid blood clearance (half-life ~1.2 hours, completely undetectable at 24 hours)
Zero bacterial colonization in normal organs including liver, spleen, lung, kidney, and heart
Only transient mild inflammatory responses, normalizing within 72 hours
No chronic toxicity during 60-day extended observation

【Future Directions】

This research has established proof-of-concept for a novel cancer therapy using natural bacteria. Future research and development will focus on:

Expansion to Other Cancer Types: Efficacy validation in breast cancer, pancreatic cancer, melanoma, and other malignancies
Optimization of Administration Methods: Development of safer and more effective delivery approaches including dose fractionation and intratumoral injection
Combination Therapy Development: Investigation of synergistic effects with existing immunotherapy and chemotherapy

This research demonstrates that unexplored biodiversity represents a treasure trove for novel medical technology development and holds promise for providing new therapeutic options for patients with refractory cancers.

###

【Glossary】

Facultative Anaerobic Bacteria: Bacteria capable of growing in both oxygen-rich and oxygen-depleted environments, enabling selective proliferation in hypoxic tumor regions.

Complete Response (CR): Complete tumor elimination confirmed by diagnostic examination following treatment.

Immune Checkpoint Inhibitor: Drugs that release cancer cell-mediated immune suppression, enabling T cells to attack cancer cells.

CD47: A cell surface protein that emits "don't eat me" signals; cancer cells overexpress this to evade immune attack.

【Publication Information】

Title: Discovery and characterization of antitumor gut microbiota from amphibians and reptiles: Ewingella americana as a novel therapeutic agent with dual cytotoxic and immunomodulatory properties

Authors: Seigo Iwata, Nagi Yamashita, Kensuke Asukabe, Matomo Sakari, Eijiro Miyako*

Journal: Gut Microbes

DOI: 10.1080/19490976.2025.2599562