Do spicy foods help or hurt your gut health?

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Jun 26 2025

A new review explains how the fiery chemical in chili peppers rewires your gut bacteria and impacts your health, for better or worse, depending on dose, diet, and your unique biology.

Review: Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health. Image Credit: S. Singha / Shutterstock

A recent paper published in the journal Metabolites reviewed the metabolism, gut microbial interactions, and physiological implications of capsaicin. Capsaicin is the main pungent alkaloid in chili peppers, consumed widely as a traditional remedy and culinary ingredient.

Various studies have reported that capsaicin can modulate inflammatory, metabolic, oncogenic, and neurological pathways, establishing it as a promising dietary phytochemical with pharmacological potential.

Emerging evidence underscores the gut microbiota as a determinant of capsaicin’s systemic impact and metabolic fate. In turn, capsaicin modulates the microbiota structure, often favoring beneficial taxa and reducing pro-inflammatory taxa. However, these effects are highly context-dependent, varying by dose, sex, host enterotype, and baseline microbiota composition.

In the present study, researchers comprehensively reviewed the metabolic pathways and systemic bioactivity of capsaicin and explored the factors affecting its pharmacological potential.

Role of gut microbiome and host metabolism in capsaicin transformation

Capsaicin is mainly absorbed in the gastrointestinal (GI) tract via passive diffusion. Absorption rates are markedly high in animal models (85% to 95%); however, capsaicin has low systemic bioavailability due to rapid metabolism, resulting in a short half-life.

After absorption, capsaicin undergoes phase 1 hepatic metabolism, catalyzed by cytochrome P450 enzymes. These enzymes facilitate aliphatic side-chain hydroxylation, generating the primary metabolites, 17-hydroxycapsaicin and 16-hydroxycapsaicin.

Another metabolic route generates 16, 17-dehydrocapsaicin via alkyl dehydrogenation; this metabolite exhibits retained high affinity to transient receptor potential vanilloid-1 (TRPV1), increasing irritancy. 16, 17-dehydrocapsaicin binds to TRPV1, but the primary metabolites exhibit altered orientations, reducing their ability to activate TRPV1.

This means that the conversion of capsaicin acts as a detoxification mechanism, diminishing its biological stimulation and pungency. The gut microbiota is gaining attention as capsaicin’s complementary metabolic system. Evidence suggests that the gut microbiota could transform capsaicin through dehydroxylation, demethylation, conjugation, and reductive cleavage reactions.

These transformations likely occur before hepatic processing or in parallel, especially in people with high microbial enzymatic activity or slower GI transit. The bioavailability of capsaicin is determined by various interrelated factors, including the route of administration, metabolic transformations, physicochemical properties, and host biological context. The formulation and route of capsaicin administration affect its absorption and systemic delivery.

While oral ingestion typically results in extensive first-pass (hepatic) metabolism, topical or transdermal application bypasses hepatic processing. Advanced formulations, such as hydroxypropyl-β-cyclodextrin, polymeric micelles, and liposomes, have been developed to overcome stability and solubility limitations. These formulations can enhance oral bioavailability, therapeutic consistency, and plasma half-life of capsaicin.

Variations in hepatic enzyme activity due to sex, age, genetic polymorphisms, and health status can influence capsaicin metabolism, resulting in inter-individual differences in exposure and response. The gut microbiota also contributes to capsaicin biotransformation in the intestinal lumen. Following hepatic conjugation, capsaicin metabolites secreted into the bile are subject to deconjugation by microbial enzymes, allowing for reabsorption and extended systemic availability.

Capsaicin Metabolism and the Central Nervous System

Critically, capsaicin crosses the blood-brain barrier and accumulates in lipid-rich brain regions (striatum, cerebellum), where it undergoes region-specific metabolism (dominant 17-hydroxycapsaicin) and modulates neurotransmitters like dopamine and acetylcholine.

Effects of capsaicin on gut microbiota

Recent studies on the interactions between the gut microbiota and capsaicin have postulated two main mechanisms. First, capsaicin was associated with a higher diversity of bacteria that produce short-chain fatty acids (SCFAs), such as propionate, acetate, and butyrate, in mice. Propionate and butyrate can inhibit histone deacetylase in intestinal epithelial and immune cells, and this inhibition negatively regulates the expression of pro-inflammatory cytokines in immune cells.

Second, capsaicin decreased the abundance of lipopolysaccharide (LPS)-producing gram-negative bacteria. LPS are components of the bacterial outer membrane that can interact with and activate the toll-like receptor 4, triggering a signaling cascade that leads to the transcription of pro-inflammatory cytokines. However, effects are dose- and sex-dependent: high doses (>80 mg/kg) cause intestinal damage in mice, while microbiota changes (e.g., enrichment of Faecalibacterium) exhibit sex-specific patterns.

Contrasting effects on Akkermansia muciniphila, increased via TRPV1-mediated mucin secretion at low doses but decreased at high doses, highlight dose sensitivity. In mice, a capsaicin-rich diet prevented microbial dysbiosis, increased SCFA-producing bacteria, and decreased LPS-producing bacteria.

Effects of capsaicin on gene and protein modulation

Capsaicin has garnered substantial attention due to its health benefits, including anti-inflammatory, antioxidant, anticancer, and anti-obesity properties. These properties have illustrated capsaicin’s role in gene regulation, inhibiting adipogenesis, increasing the expression of glycolytic enzymes, and enhancing energy metabolism.

Notably, anti-obesity effects may occur independently of TRPV1 activation through microbiota-mediated pathways. Various studies have also tested capsaicin as a potential therapeutic alternative against cancer proliferation via cell death induction.

Capsaicin can inhibit lysine-specific demethylase 1A, which is overexpressed in multiple cancers and is associated with cancer cell progression. Notably, capsaicin acts as a "double-edged sword" in oncology: while it induces apoptosis via STAT3/TRIB3 pathways and inhibits topoisomerases in cancers, high-dose or long-term exposure promotes gastric tumor progression and metastasis in mice through microbiota-driven increases in serotonin.

The anti-obesity properties of capsaicin have been linked to uncoupling proteins, which induce activity during energy expenditure and increase thermogenesis.

Capsaicin has been shown to reduce oxidative stress and redox imbalance through the regulation of the circadian clock (Bmal1) and TRPV1/PKA pathways. Studies have also reported that capsaicin could attenuate neurodegeneration in mice by decreasing amyloid-β levels and modulating region-specific neurotransmitter dynamics (e.g., hippocampal acetylcholine).

Concluding remarks

Taken together, capsaicin is a multifunctional phytochemical, and its effects on host physiology are influenced by its bioavailability, metabolic transformations, and gut microbiota. Capsaicin has diverse systemic effects and can modify the gut microbiota composition, promoting beneficial taxa and reducing harmful taxa. These host-microbiota interactions suggest that capsaicin might be a selective microbiota-shaping agent and metabolic modulator.

Critical unresolved questions include long-term stability of microbiota changes, mechanisms of microbial biotransformation, and context-specific risks (e.g., tumor promotion at high doses). Further studies are required to elucidate the underlying mechanisms that could help advance capsaicin as a dietary and therapeutic agent.