A novel triterpenoid from Alisma orientale alleviates OVA-induced allergic asthma through a gut microbiota-acetate-FFAR2 immunoregulatory axis involving increased Lactobacillus murinus abundance, elevated acetate levels, enhanced FFAR2 signaling, and restoration of Th17/Treg balance.
Key Findings
Results
The novel triterpenoid (Tri) from Alisma orientale markedly attenuated key features of allergic asthma in ovalbumin-induced mice.
Tri reduced airway hyperresponsiveness, inflammatory cell infiltration, and collagen deposition in asthmatic mice.
Tri decreased production of asthma-related inflammatory mediators in the OVA-induced mouse model.
Histopathological changes associated with allergic asthma were ameliorated by Tri treatment.
The model used ovalbumin (OVA) sensitization and challenge to induce allergic asthma.
Results
The protective effects of Tri against allergic asthma were dependent on gut microbiota.
Anti-asthmatic effects of Tri were attenuated after gut microbiota depletion.
The protective effects were partially transferred by fecal microbiota transplantation (FMT) from Tri-treated mice.
These findings implicate gut microbiota as a necessary mediator of Tri's therapeutic actions.
Gut microbiota depletion and FMT experiments were key mechanistic tools used to establish microbiota dependence.
Results
Tri restored gut microbial homeostasis and specifically increased the abundance of Lactobacillus murinus.
16S rDNA sequencing was used to characterize gut microbiota composition changes associated with Tri treatment.
Tri treatment increased the relative abundance of Lactobacillus murinus among other microbial changes.
Gut microbial homeostasis was restored by Tri in OVA-induced asthmatic mice.
Supplementation with Lactobacillus murinus alone reproduced the anti-asthmatic effects of Tri.
Results
Tri elevated short-chain fatty acids, particularly acetate, as key microbial metabolites mediating its anti-asthmatic effects.
Targeted short-chain fatty acid (SCFA) analysis was performed to characterize metabolic changes associated with Tri treatment.
Acetate was identified as the principal SCFA elevated by Tri treatment.
Direct acetate supplementation reproduced the anti-asthmatic effects of Tri in vivo.
Both Lactobacillus murinus supplementation and acetate intervention were associated with upregulation of FFAR2 and restoration of Th17/Treg balance.
Results
Tri and acetate exerted immunoregulatory effects through free fatty acid receptor 2 (FFAR2) signaling.
Lung transcriptomic profiling was used to identify FFAR2 as a key signaling mediator.
A co-culture system of 16HBE cells and bone marrow-derived dendritic cells (BMDCs) was used to assess FFAR2 involvement in vitro.
FFAR2 silencing attenuated the immunoregulatory effects of Tri and acetate in the co-culture system.
FFAR2 overexpression further supported FFAR2 involvement in the immunoregulatory actions associated with Tri and acetate.
The authors noted that further loss-of-function studies are required to establish direct causality.
Results
Tri and acetate restored Th17/Treg immune balance in the context of allergic asthma.
Supplementation with Lactobacillus murinus or acetate was associated with restoration of the Th17/Treg balance.
Immune dysregulation, specifically Th17/Treg imbalance, is characterized in the paper as a hallmark of allergic asthma pathogenesis.
FFAR2 upregulation was associated with the restoration of Th17/Treg balance following Tri, Lactobacillus murinus, or acetate treatment.
The gut microbiota-acetate-FFAR2 axis was proposed as the mechanistic pathway linking Tri treatment to immune restoration.
Background
Gut microbiota-derived metabolites, particularly SCFAs, are implicated in the pathogenesis of allergic asthma and the mechanism of action of natural product treatments.
The paper states that 'increasing evidence implicates gut microbiota-derived metabolites in its pathogenesis' of allergic asthma.
The authors noted that 'the microbial and metabolic mediators underlying the anti-asthmatic effects of natural products remain insufficiently defined' prior to this study.
The study combined 16S rDNA sequencing, targeted SCFA analysis, and lung transcriptomics to characterize microbiota-associated changes.
The novel triterpenoid was isolated from Alisma orientale, a natural product source.
What This Means
This research investigated how a newly identified compound (called Tri) extracted from the medicinal plant Alisma orientale can protect against allergic asthma. Using a mouse model where asthma was triggered by exposure to egg white protein (ovalbumin), the researchers found that Tri significantly reduced the key features of asthma, including airway oversensitivity, immune cell buildup in the lungs, scar-like tissue changes, and elevated levels of inflammation-promoting molecules. Importantly, when the researchers wiped out the gut bacteria in the mice using antibiotics, Tri largely lost its protective effects — and those effects could be partially restored by transferring gut bacteria from Tri-treated mice to untreated asthmatic mice, demonstrating that the gut microbiome plays a central role in how Tri works.
The researchers traced the mechanism through a specific chain of events: Tri increased the abundance of a beneficial gut bacterium called Lactobacillus murinus, which in turn produced higher levels of a short-chain fatty acid called acetate. When the researchers directly gave mice either Lactobacillus murinus or acetate supplements (without Tri), they observed similar anti-asthmatic benefits. Both treatments were linked to activation of a receptor on immune cells called FFAR2 (free fatty acid receptor 2) and a rebalancing of two types of immune cells — Th17 cells (which promote inflammation) and Treg cells (which suppress it) — that are dysregulated in asthma. Cell culture experiments in which FFAR2 was either blocked or overactivated confirmed that this receptor is involved in the immune effects of Tri and acetate.
This research suggests that the gut-lung connection is an important pathway for treating allergic asthma, and that natural compounds like Tri may work not just directly in the lungs but by reshaping the gut microbial environment to produce beneficial metabolites. The identified gut microbiota-acetate-FFAR2 axis could represent a target for future asthma therapies, though the authors themselves note that additional experiments are needed to definitively prove that each step in this chain directly causes the observed benefits.
Zeng M, Feng A, Zhang B, Li S, Guo P, Zhu D, et al.. (2026). A novel triterpenoid from Alisma orientale alleviates allergic asthma through the gut microbiota-acetate-FFAR2 immunoregulatory axis.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116809