Honeysuckle nanovesicles reduced gut inflammation and restored microbial and immune balance in colitis models, suggesting a microbiota-based therapy.
(Nanowerk Spotlight) The human gut contains a dense and highly active microbial community. Trillions of bacteria, viruses, and other microscopic organisms live there, influencing not only digestion but also immune responses, nutrient absorption, and the maintenance of tissue health. When the structure or function of this microbial population is disrupted, the consequences can be widespread.
Inflammatory bowel disease, which includes ulcerative colitis and Crohn’s disease, is one example. It involves persistent inflammation in the digestive tract, damage to the gut lining, and an immune system that responds inappropriately to its own environment. Current treatments can reduce symptoms, but they rarely address the underlying dysfunction, and many come with significant risks or long-term complications.
Efforts to treat inflammatory bowel disease by directly altering the gut microbiota have had limited and often unpredictable outcomes. While approaches like probiotics and fecal microbiota transplants aim to restore a healthier microbial composition, their effects can vary widely between individuals.
In many cases, the changes are short-lived or fail to produce lasting clinical improvement. These methods also face practical challenges, including the difficulty of delivering live microbes through the digestive tract and the lack of standardization in microbial preparations.
This gap in treatment options has drawn attention to less conventional approaches. One area of focus involves naturally occurring particles released by plant cells. These nanovesicles are microscopic, membrane-bound packages that carry proteins, RNA, and other biologically active molecules. They are produced in many edible plants and are stable enough to survive digestion. Early studies have shown that some plant-derived nanovesicles can reduce inflammation, support tissue repair, and influence the behavior of both microbes and host cells.
In this context, researchers have turned to honeysuckle, a plant widely used in traditional Chinese medicine for its anti-inflammatory effects. Honeysuckle is also the key ingredient in Peach Blossom Soup, a traditional herbal formula used to treat intestinal disorders. Rather than study the plant in its crude form, the researchers focused on isolating its nanovesicles to evaluate their specific biological effects. The question was whether these purified particles could be used to restore microbial and immune balance in a model of inflammatory bowel disease.
The results point to a complex but coordinated set of effects involving immune cells, microbial metabolites, and intestinal structure. The work also raises the possibility that nanovesicles from edible plants could provide a new way to influence gut health through targeted, biologically active delivery.
Identification and characterization of honeysuckle exosome-like vesicles (HNVs). A) HNVs were isolated and purified following a detailed and standardized protocol. B) TEM (upper panel) and Cryo-TEM (lower panel) imaging of HNVs. C–D) DLS analysis showing C) zeta potential and D) size distributions of HNVs. E) Counting of HNVs particles by nanoparticle tracking analysis (NTA). F–G) Changes in size distribution of HNVs after incubation with F) gastric juice and G) intestinal juice at 37 °C. H) Quantification of HNVs protein concentration by Bradford assay. Scale bar = 200 nm. (Image: Reprinted from DOI:10.1002/advs.202505208, CC BY) (click on image to enlarge)
The researchers began by extracting and characterizing the nanovesicles from honeysuckle juice. These particles were roughly 100 to 200 nanometers in size and stable in simulated digestive fluids. They contained a mix of lipids, proteins, and microRNAs. When administered to mice with chemically induced colitis, the honeysuckle nanovesicles led to clear improvements in disease markers. Treated mice showed less weight loss, longer colons, and significantly reduced tissue damage. Inflammatory cytokines were reduced in both blood and colon tissue, and the balance between pro-inflammatory and regulatory immune cells shifted in a favorable direction.
One key finding was that the nanovesicles helped preserve the physical structure of the gut lining. Proteins that form tight junctions between intestinal cells were more abundant, and mucus-producing goblet cells were better maintained. These changes suggest that the treatment helped repair and protect the gut barrier, which is often compromised in inflammatory bowel disease.
The nanovesicles also appeared to influence the composition and function of the gut microbiota. DNA sequencing revealed that they increased the abundance of bacteria associated with beneficial metabolic activity, including Eubacterium and Turicibacter, while reducing the levels of potentially harmful genera such as Escherichia-Shigella. These shifts were accompanied by changes in microbial metabolites. Levels of short-chain fatty acids, especially acetate and butyrate, were higher in treated mice. These fatty acids are known to support epithelial health and modulate immune responses. Bile acid profiles were also altered, suggesting broader effects on metabolic signaling in the gut.
Transcriptomic analysis showed that honeysuckle nanovesicles downregulated genes associated with chemokine signaling, a pathway that recruits immune cells to sites of inflammation. They also reduced activity in cyclic AMP signaling, which can affect both barrier function and immune cell behavior. These changes likely contribute to the observed reductions in immune cell infiltration and tissue damage.
To confirm that the therapeutic effects depended on interactions with the gut microbiota, the researchers tested the nanovesicles in mice whose gut bacteria had been depleted with antibiotics. In these animals, the nanovesicles no longer improved colitis symptoms or protected gut structure. However, when fecal material from nanovesicle-treated mice was transplanted into microbiota-depleted mice, the protective effects returned. This indicates that the treatment works in part by reshaping the microbial ecosystem and its metabolic outputs.
Interestingly, transplants of heat-inactivated fecal material—lacking live bacteria—were also effective, and in some cases even more so than transplants containing live microbes. This suggests that microbial metabolites or structural components, rather than the living bacteria themselves, may play a key role. Analysis of these transplants found higher levels of compounds associated with immune regulation and barrier repair, including bile acid derivatives and lysophospholipids.
This study provides detailed evidence that honeysuckle-derived nanovesicles can reduce inflammation and promote gut repair through multiple coordinated mechanisms. These include modifying the microbiota, enhancing the production of beneficial microbial metabolites, restoring immune cell balance, and protecting the intestinal barrier. The particles are orally deliverable, biologically stable, and derived from an edible plant, which supports their potential for safe use in therapeutic settings.
While this work was conducted in animal models, it introduces a framework for developing plant-based nanovesicle therapies that target both microbial and immune components of disease. Future research will need to clarify which molecules in the nanovesicles drive these effects, how they interact with specific cell types, and whether the findings extend to human disease. For now, the study adds to a growing body of research suggesting that plant nanovesicles represent a distinct and potentially versatile class of biological tools for modulating inflammation and microbial balance in the gut.
For authors and communications departmentsclick to open
Lay summary
Prefilled posts
ORCID information
Huiyu Liu (Beijing University of Chemical Technology)
, 0000-0003-4465-8501 corresponding author
Nanowerk Newsletter
Get our Nanotechnology Spotlight updates to your inbox!
Thank you!
You have successfully joined our subscriber list.
Become a Spotlight guest author! Join our large and growing group of guest contributors. Have you just published a scientific paper or have other exciting developments to share with the nanotechnology community? Here is how to publish on nanowerk.com.
