Dietary capsaicin attenuates aortic dissection by activating TRPV1 to suppress TLR4/MyD88/NF-κB signalling and inhibiting M1 macrophage polarisation, accompanied by restoration of gut microbiota homeostasis and improved intestinal barrier function.
Key Findings
Results
Patients with aortic dissection had lower spicy food consumption and reduced serum capsaicin concentrations compared to individuals with AD risk factors but no disease.
50 patients with AD (AD group) and 50 volunteers with risk factors for AD (NP group) were enrolled in the clinical component of the study.
AD patients exhibited lower spicy food consumption than the NP group.
Serum capsaicin concentrations were reduced in the AD group relative to the NP group.
The clinical findings suggest an inverse association between capsaicin exposure and AD occurrence.
Results
Patients with aortic dissection exhibited gut microbiota dysbiosis compared with the non-patient risk-factor group.
Gut microbiota composition differed between the AD group and the NP group in the human cohort.
Dysbiosis in the AD group was identified through microbiota profiling of the 50 AD patients versus 50 NP volunteers.
This finding was consistent with subsequent mouse model data showing gut microbiota alterations in AD.
Results
Dietary capsaicin attenuated AD pathogenesis in a β-aminopropionitrile (BAPN)-induced mouse model of aortic dissection.
A BAPN-induced AD mouse model was used to assess the in vivo effects of capsaicin.
Capsaicin treatment reduced AD pathogenesis in mice compared to untreated AD model animals.
The protective effects of capsaicin were abrogated by the TRPV1 antagonist capsazepine, confirming TRPV1 dependence.
Capsazepine co-administration was used as an in vivo mechanistic confirmation step.
Results
Capsaicin suppressed M1 macrophage polarisation both in vivo and in a lipopolysaccharide-induced in vitro model.
A lipopolysaccharide (LPS)-induced M1 macrophage polarisation model was established to study capsaicin's mechanism in vitro.
Capsaicin inhibited M1 macrophage polarisation in the in vitro system.
In vivo, dietary capsaicin also suppressed M1 macrophage polarisation in BAPN-induced AD mice.
Inhibition of M1 macrophage polarisation was identified as a key mechanism underlying capsaicin's protective effects against AD.
Mechanistic pathway was identified using in vitro transcriptomic sequencing and small interfering RNA (siRNA) experiments.
Capsaicin was shown to activate the TRPV1 receptor, which in turn suppressed TLR4/MyD88/NF-κB signalling.
Suppression of TLR4/MyD88/NF-κB signalling resulted in inhibition of M1 macrophage polarisation.
TRPV1 antagonist capsazepine abrogated the protective effects of capsaicin in vivo, confirming that TRPV1 activation is required for the observed benefits.
Results
Dietary capsaicin restored gut microbiota homeostasis and improved intestinal barrier function in AD mice.
Capsaicin treatment in BAPN-induced AD mice restored gut microbiota homeostasis compared to untreated AD animals.
Improved intestinal barrier function was observed alongside gut microbiota restoration following capsaicin treatment.
These findings represent the first reported evidence that dietary capsaicin attenuates AD with accompanying restoration of gut microbiota homeostasis.
Gut microbiota modulation was described as an effect accompanying, rather than the primary driver of, the capsaicin-mediated protection.
What This Means
This research suggests that eating spicy food containing capsaicin — the compound that makes chili peppers hot — may help protect against aortic dissection, a life-threatening condition where the inner layer of the body's main artery tears. The study found that patients who had suffered an aortic dissection consumed less spicy food and had lower blood levels of capsaicin than people who had similar risk factors but no aortic dissection. People with aortic dissection also had an unhealthy imbalance in their gut bacteria (gut microbiota dysbiosis) compared to the risk-factor group.
Using mouse models, the researchers showed that capsaicin reduced the severity of aortic dissection and calmed down a specific type of immune response involving 'M1 macrophages' — inflammatory immune cells that play a role in damaging the aortic wall. The mechanism works through a receptor called TRPV1 (the same receptor responsible for sensing heat and spiciness), which when activated by capsaicin, shuts down an inflammatory signaling pathway (TLR4/MyD88/NF-κB). When researchers blocked TRPV1 with a drug called capsazepine, capsaicin's protective effects disappeared, confirming that the whole mechanism depends on TRPV1 activation. Capsaicin also restored healthy gut bacteria balance and improved the integrity of the intestinal lining in the mouse models.
This research suggests that dietary capsaicin could represent a promising strategy to reduce the risk or progression of aortic dissection, acting through both anti-inflammatory effects and beneficial changes in the gut microbiome. Because current medical treatments for aortic dissection are limited largely to surgery, identifying a dietary compound with protective properties is notable, though further clinical research would be needed to confirm these effects in humans.
Lan W, Yang H, Liu W, Li C, Luo C, Shi Y, et al.. (2026). Dietary capsaicin attenuates aortic dissection by inhibiting M1 macrophage polarisation and modulating the gut microbiota.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158269