The mucus layer, constituting the primary interface between the gut microbiota and host epithelium, performs multiple physiological functions beyond acting as a simple physical barrier, including providing a habitat for microorganisms, regulating the exchange of metabolic products, and coordinating immune responses^1,2. This layer is a key determinant of the stability of the gut ecosystem, and structural or chemical perturbations of the mucus layer have been reported as early indicators of increased intestinal permeability, chronic inflammation, and metabolic disorders². Therefore, understanding the factors that regulate mucus layer homeostasis is essential for characterizing the health of the gut environment.

Dietary factors are recognized as major external variables that modify the composition and function of the mucus layer. Capsaicin, the principal bioactive compound in spicy foods, has emerged as a modulator capable of directly influencing mucus layer ecology. Experimental studies evaluating the physiological effects of spicy foods have shown that capsaicin increases muc2 expression in intestinal epithelial cells and promotes the expansion of mucin-utilizing microbial taxa, thereby supporting mucus-layer regeneration and stability^3,4. Capsaicin has also been reported to enhance short-chain fatty acid (SCFA) biosynthesis pathways and regulate host energy metabolism⁵, suggesting a role as a metabolic mediator that strengthens interactions between the host and gut microbiota. However, the findings across various studies are inconsistent^6–8. In rodents given high doses of capsaicin (40 mg/kg), mucosal irritation and barrier disruption were evident⁹, whereas human intervention studies have shown discomfort at low doses (0.75 mg/day) and metabolic improvements at higher doses (135 mg/day)^10,11, indicating that the physiological response to capsaicin is not a linear dose-dependent relationship.

Similarly, epidemiological studies have reported associations between spicy food intake and reduced all-cause mortality and metabolic disease risk^12–14, although these associations remain inconsistent across populations. This inconsistency is likely attributable to the co-consumption of spicy foods with other dietary factors, such as high-fat meals or alcohol, which may modify or obscure the intrinsic effects of capsaicin¹⁵. Thus, the influence of spicy food consumption on the mucus layer and microbial function requires evaluation within the broader context of real-world dietary patterns, emphasizing the need for analytical approaches that can quantitatively capture such contextual variation.

Most prior studies of the gut microbiota have been based on 16S rRNA sequencing, which provides insights into microbial composition and diversity but offers limited resolution for interpreting functional regulation at the metabolic pathway level, particularly for mucus-related gene clusters or SCFA biosynthetic pathways that are directly linked to gut barrier homeostasis¹⁶. Consequently, these approaches are insufficient for evaluating the ecological significance of dietary exposure. In contrast, shotgun metagenomics enables the direct profiling of microbial genes and functional characterization of metabolic networks modulated by dietary factors, including spicy food intake^17,18.

In this study, we performed shotgun metagenomic profiling of a cohort of more than 200 healthy Korean adults to investigate the mucus-associated metabolic pathways and functional features of the gut microbiota in relation to the frequency of consumption of spicy food. The goal was to characterize how food intake influences the microbial networks involved in mucus utilization, SCFA production, and intestinal barrier maintenance. By interpreting the relationship between spicy food consumption and the gut ecosystem at both structural and functional levels, this study provides a basis for a more refined understanding of the physiological mechanisms through which dietary habits contribute to gut barrier homeostasis.

Spicy food is known to stimulate gastrointestinal physiological responses and mucus secretion, producing both beneficial and adverse health effects^6–8, whereas alcohol consumption has been reported as a representative disruptor of the intestinal barrier, inducing epithelial injury and suppressing mucus secretion^19,20. Considering these prior findings, we designed the present study with the aim of evaluating how these two dietary factors are associated with markers of epithelial injury and the composition of the gut microbiota.

We first assessed, through analysis of Spearman’s correlation, the relationships between survey-based demographic, dietary, and lifestyle variables and a number of biomarkers: I-FABP and L-FABP, reflecting intestinal barrier damage; inflammatory markers (TNF-α and IL-6); and the sensory receptor for pungency (TRPV1). In the biomarker assessment, TNF-α, IL-6, and TRPV1 were detected at low concentrations and were therefore excluded from subsequent analyses (Supplementary Fig. 1).

Analysis of the Spearman’s correlation between demographic variables and epithelial injury markers showed that I-FABP exhibited weak positive correlations with age (ρ = 0.22), BMI (ρ = 0.19), and stool frequency (ρ = 0.24), and a negative correlation with sex (ρ = − 0.27) (Fig. 1B). L-FABP showed a positive correlation with I-FABP (ρ = 0.31), suggesting that the two markers reflect similar epithelial injury responses. Examination of correlations between dietary factors and biomarkers revealed that alcohol intake (g/day) was positively correlated with I-FABP (ρ = 0.26), whereas no correlation was observed with L-FABP (ρ = 0.05). Spicy food intake showed little association with I-FABP (ρ = 0.01) or L-FABP (ρ = 0.05), and the same was true for other dietary variables.

These patterns suggest that alcohol consumption represents a dietary factor exerting a more direct and sensitive influence on intestinal epithelial injury. Accordingly, the interpretation of gut microbial composition and functional pathway changes requires analytical strategies that incorporate alcohol intake as a principal independent variable while simultaneously adjusting for sex, age, BMI, and stool frequency as confounders. This approach enables a clearer separation of the effects of spicy food versus alcohol consumption and provides a more accurate framework for explaining the physiological variations reflected by epithelial injury markers.

Besides, alcohol exhibited some correlation (although weak) with high-fat and instant food intake, indicating that it may be part of a broader cluster of co-occurring dietary behaviors. Alcohol intake also showed a weak positive correlation with consumption of instant foods (ρ = 0.22) and preference for high-fat foods (ρ = 0.20). Lifestyle variables such as smoking, physical activity, and sleep quality were not correlated with either I-FABP or L-FABP.

Gut microbiome profiles were generated by shotgun metagenomic sequencing of fecal samples collected from 229 participants (Supplementary Fig. 2A). A total of 1,527 species were detected across all samples, and the two phyla commonly reported to be dominant in the human gut microbiome, Bacillota and Bacteroidota, were the most abundant²¹. When evaluating the extent to which environmental and dietary factors contributed to the taxonomic variation, sex, stool frequency, and age showed the highest explanatory power, followed by BMI, I-FABP levels, smoking, and alcohol consumption (Fig. 2A). In contrast, other factors, including meat–vegetable preference, vitamin intake, and sleep quality, explained less than 1% of the variation in microbial community composition.

To determine the gut microbial composition as it relates to spicy food consumption, participants were classified as high-intake (SH; n = 40) or low-intake (SL; n = 189) based on consumption frequency. The SH group showed significantly higher spicy food intake scores than did the SL group (p < 0.001), whereas fast-food consumption was significantly lower (p = 0.003). There were no differences between the groups in terms of demographic or lifestyle variables, including age, BMI, stool frequency, or alcohol consumption. No significant differences were observed for other health-related factors, such as use of vitamins, probiotics, or antibiotics (Supplementary Table 1). Shotgun metagenome–based diversity analyses showed no distinct separation in alpha diversity, and Bray–Curtis distance–based principal coordinates analysis (PCoA) also indicated no clear separation of taxonomic composition between the groups (PERMANOVA, p = 0.09) (Supplementary Fig. 2C).

Species-level differential abundance was assessed using MaAsLin2 with a linear mixed-effects model, which identified 21 species with significant group differences (Fig. 2C). The SH group showed significantly higher abundances of the following microbial taxa: Dialister invisus, Blautia_A caecimuris, Limisoma sp000437795, Ruminococcus_E sp003526955, Dorea_A longicatena_B, Faecalimonas phoceensis, Blautia hansenii, Anaerotignum sp001304995, Blautia sp001304935, Amedibacillus dolichus, Eubacterium_R sp000436835, Blautia_A sp900549015, Phocaeicola sp900542985, Butyribacter sp001916135, Butyricicoccus pullicaecorum, CAG-83 sp000435975, and Fusobacterium_A mortiferum. Among these taxa, species of the genera Blautia, Limisoma, Ruminococcus, Butyribacter, and Butyricicoccus are associated with SCFA production and mucus layer metabolism^4,22–25, suggesting that spicy food intake may contribute positively to gut metabolic homeostasis. However, species of Fusobacterium have been linked to intestinal inflammation²⁶ and genera such as Dialister and Dorea have been shown to have context-dependent associations with health in metagenomic studies^27–31. In contrast, the SL group showed significantly higher abundances of Dialister hominis, Lawsonibacter asaccharolyticus, UMGS856 sp900546265, and Gordonibacter pamelaeae. Lawsonibacter is a known butyrate producer³², and Gordonibacter is associated with ellagic acid metabolism³³.

Next, participants were classified according to their daily alcohol intake (g/day) into a high-consumption group (DH; n = 109) and a low-consumption group (DL; n = 120). The DH group showed a markedly higher alcohol intake than did the DL group (p < 0.001), and the proportion of smokers was also significantly higher (p < 0.001). Among the dietary variables, consumption of spicy food (p = 0.034), high-fat food (p = 0.014), and instant food (p = 0.003) was higher in the DH group. No significant differences were observed between the groups in terms of age, BMI, stool frequency, Bristol stool score, abdominal pain, sleep quality, or other demographic and lifestyle variables (Supplementary Table 1). Shotgun metagenome–based diversity analyses showed no distinct separation in either alpha or beta diversity between the groups (PERMANOVA, p = 0.241) (Supplementary Fig. 2C).

MaAsLin2 analysis of species-level differences identified 18 microbial taxa that were significantly associated with alcohol consumption (Fig. 2D). In the DH group, Faecalimonas umbilicata, Amedibacillus dolichus, Lawsonibacter sp900545895, Evetepia excrementipullorum, Weissella koreensis, Butyricicoccus pullicaecorum, Fimisoma sp000435715, and Frisingicoccus caecimuris were significantly enriched. Species belonging to Lawsonibacter and Butyricicoccus have been reported to be butyrate producers^32,34, and species of Weissella are lactic acid bacteria originating from kimchi³⁵. The presence of certain beneficial taxa in the DH group may reflect ecological selection under alcohol-induced stress conditions, wherein species capable of surviving or adapting to such environments persist or show an increase in their relative abundance^36,37. In the DL group, the following strains were relatively abundant: CAG-83 sp900548615, CAG-95 sp900066375, CAG-103 sp900543625, CAG-170 sp900553545, Blautia_A sp900066355, Alistipes_A ihumii, Ventricola sp900542395, Limivivens sp900543575, Lawsonibacter sp014287875, and Gemmiger sp900539695. Notably, species of Alistipes and Blautia possess SCFA-producing and mucin-degrading capacities that may support the maintenance of mucosal homeostasis³⁸. The distinction in I-FABP levels between the spicy food- and alcohol-defined groups further supports the notion that dietary factors may differentially influence intestinal epithelial injury (Fig. 2B). I-FABP and L-FABP levels did not differ significantly between the SH and SL groups; in contrast, I-FABP levels were significantly higher in the DH group than in the DL group (p = 0.004).

To explore the global metabolic potential of the gut microbiome, unstratified KEGG and MetaCyc pathway abundances were computed using HUMAnN 3.0, followed by MaAsLin2 analysis (Fig. 4). In total, 38 major pathways exhibited differential distributions among the four groups. Based on the MetaCyc ontology, these pathways were categorized into amino acids, carbohydrates, lipids, cofactors, nucleotides, aromatic compounds, secondary metabolites, and energy metabolism.

The DHSH group was characterized by carbohydrate metabolic pathways, such as hexitol fermentation to lactate, formate, ethanol, and acetate (P461-PWY) and acetyl-CoA fermentation to butanoate II (PWY-5676), along with amino acid metabolic pathways, including L-isoleucine biosynthesis III (PWY-5103) and the super-pathway of L-serine and glycine biosynthesis I (SER-GLYSYN-PWY). The formaldehyde assimilation III (P185-PWY) pathway was also enriched in this group.

The DLSH group showed a prominent enrichment of amino acid metabolism pathways, such as L-methionine biosynthesis I (HOMOSER-METSYN-PWY) and L-alanine fermentation to propanoate and acetate (PROPFERM-PWY), but also exhibited a broader diversity of pathways related to lipid, energy, and cofactor metabolism than was evident in the other groups. Notably, aromatic compound degradation pathways, including catechol degradation I (meta-cleavage pathway) (PWY-5415) and 4-hydroxyphenylacetate degradation (3-HYDROXYPHENYLACETATE-DEGRADATION-PWY) were detected.

The DHSL group displayed relatively few distinct features, with L-proline biosynthesis II (from arginine) (PWY-4981) emerging as the dominant amino acid pathway. The DLSL group showed higher abundance of cofactor-related pathways, such as coenzyme A biosynthesis I (COA-PWY) and super-pathway of thiamine diphosphate biosynthesis I (THISYN-PWY), as well as nucleotide metabolism pathways, including inosine-5'-phosphate biosynthesis I (PWY-6123).

To assess the activation status of short-chain fatty acid (SCFA)-producing pathways, species-level stratified KEGG ortholog (KO) profiles were compared between the groups (Fig. 5A). SCFA-related genes were analyzed based on a previously established list of SCFA-producing-associated KOs³⁹. Group-wise comparison revealed that the DHSH group exhibited the highest overall abundance of gene families associated with acetate, propionate, and butyrate production (K00925, K01738, K16363, K01646, K19697, K01034, K01443, and K02535). The major contributing species were Anaerostipes hadrus, Blautia hansenii, Escherichia coli, and Fusobacterium mortiferum. Similarly, the DLSH group showed elevated abundance of acetate-, propionate-, and butyrate-producing gene families (K01026, K00929, and K00138, respectively), with Blautia obeum, Blautia producta, and Klebsiella pneumoniae identified as key contributors. In contrast, the DLSL group displayed a high abundance of the acetate-producing KO K16363 associated with Bacteroides nordii, whereas the propionate- and butyrate-producing pathways were comparatively reduced. The DHSL group exhibited only a limited presence of SCFA production–related genes, suggesting relatively weak activation of these metabolic pathways.

In this study, we evaluated how spicy food consumption and alcohol intake differentially influence intestinal epithelial injury, dietary and lifestyle factors, and gut microbial composition in healthy adults. Among the epithelial injury markers, I-FABP exhibited significant correlations with age, BMI, stool frequency, and sex, indicating that subtle epithelial damage signals are strongly influenced by demographic and physiological factors (Fig. 1B). In contrast, spicy food consumption frequency showed no association with either I-FABP or L-FABP, and no linkage was observed between FABP-based injury markers and spicy sensitivity or pain responses. These findings suggest that typical levels of spicy food consumption in healthy adults do not induce noticeable structural intestinal damage.

However, alcohol intake showed a clear positive correlation with I-FABP, consistent with previous reports linking alcohol to epithelial cytotoxicity, reduced mucus secretion, and weakened barrier function^41,42. In contrast, the L-FABP levels did not correlate with alcohol consumption. This pattern suggests that alcohol consumption may directly trigger the release of I-FABP, which is exclusively expressed in small intestinal enterocytes, thereby providing a more specific indication of alcohol-induced enterocyte disruption. As L-FABP is expressed across multiple organs, its association with alcohol may be less readily captured in a cross-sectional setting, potentially limiting its sensitivity to alcohol-specific epithelial disturbances^19,43.

Urinary inflammatory cytokine and oral epithelial TRPV1 expression were assessed to characterize systemic inflammation and receptor expression^44,45, but both were detected at low concentrations across samples (Supplementary Fig. 1A). This is consistent with previous reports that healthy adults have low basal cytokine levels and limited detectability^45,46, reinforcing I-FABP as a relatively stable epithelial injury marker under the conditions of this study.

Based on shotgun metagenomic analyses, distinct species-level differences were observed when participants were grouped separately by spicy food or alcohol intake (Fig. 2A–B). In the high-spicy food group (SH), increases were observed in Blautia, Limosima, Ruminococcus, Butyribacter, and Butyricicoccus, taxa associated with SCFA production and mucin metabolism^4,22–25. These findings suggest that spicy food intake may selectively influence the mucus layer-associated metabolic pathways, supporting hypotheses from studies showing capsaicin-induced stimulation of mucin production⁴. Conversely, increases in Fusobacterium_A mortiferum, Dialister, and species of Dorea, taxa with context-dependent or bidirectional health associations^26–31, demonstrate that spicy food may act as a complex stimulus capable of eliciting both beneficial and adverse signals, in line with the mixed findings of previous research^6–8.

Changes observed in the high-alcohol-intake group (DH) differed markedly. Although some taxa typically considered beneficial, including Butyricicoccus, Lawsonibacter, and Weissella, were enriched^32,34,35, this was in contrast to the DL group, which showed a greater abundance of SCFA-producing and mucin-degrading taxa such as Alistipes and Blautia³⁸. Notably, the epithelial injury marker I-FABP was not different between spicy food groups, but was significantly elevated only in the high-alcohol-intake group (p = 0.004), supporting the interpretation that alcohol exerts a more direct effect on epithelial injury than spicy food. Thus, the presence of beneficial taxa in the DH group may reflect ecological persistence under alcohol-derived stress, rather than improved gut function^36,37. Taken together, our results indicate that the intake of spicy food induces variable and mixed shifts within metabolic and mucus-related microbial networks, whereas alcohol intake produces distinct alterations, particularly in pathways linked to mucin metabolism. These findings indicated that spicy foods and alcohol may influence the gut ecosystem through mechanistically divergent routes.

When participants were categorized into four combined spicy food–alcohol groups (DLSL, DLSH, DHSL, and DHSH), the overall microbial diversity did not differ significantly across groups, and Bray–Curtis PCoA analyses showed no distinct clustering (Supplementary Fig. 1B–C). Nonetheless, functional pathways related to mucin metabolism and SCFA production were clearly differentiated according to spicy food intake, suggesting that although the global taxonomy remains stable, metabolic network configurations diverge more strongly when spicy food and alcohol exposure intersect (Fig. 3, Fig. 4, Fig. 5). The high-spicy groups (DHSH and DLSH) were enriched in the genera Blautia, Roseburia, Coprococcus, and Limisoma, taxa known to support combined fiber–mucin utilization and SCFA production^4,22–24. Their presence aligns with the previously defined fiber–mucin coupling metabotypes 1–2, which represent homeostatic states sustaining both mucin turnover and epithelial energy supply⁴⁰. This interpretation was reinforced by functional metagenomic analyses, which showed differential activation of mucin-degrading pathways and SCFA-related gene families in high-spicy groups (Figs. 4 and 5A–B). These results support the hypothesis that spicy foods exert compensatory or modulatory effects on gut metabolic networks that are otherwise perturbed by alcohol exposure. Given that mucin turnover critically relies on cross-feeding among SCFA-producing bacteria⁴⁷, the observed patterns suggest that spicy food intake, regardless of alcohol consumption, modulates the abundance of genes related to butyrate production, including buk (K00929) and bup (K01034) (Fig. 5B). In particular, the Blautia producta-associated butyrate kinase gene buk (K00929) was enriched in the DLSH group, whereas the Fusobacterium mortiferum-associated butyrate phosphotransferase gene bup (K01034) was specific to the DHSH group. In the DHSH group, enhanced carbohydrate metabolism (PWY-5676, P461-PWY), sulfate reduction (K00394, K00395, K00956), and glycosidase pathways (GH13–GH5 families), along with β-galactosidase (K01491) and galactokinase (K00965), suggested an active mucin degradation–SCFA production flux. Blautia hansenii and Anaerostipes hadrus appeared to sustain the acetate–propionate flux (Fig. 5A–B), indicating the active turnover of sulfo-mucin-derived sulfate, mucin glycan degradation, and SCFA production⁴⁰. In contrast, the DHSL group was characterized by enrichment of Clostridium_Q species, known H₂S producers, whereas the DHSH group contained H₂S consumers and SCFA producers such as Anaerostipes hadrus (Fig. 3A, Fig. 5B). This pattern implies a disrupted cross-feeding flux in DHSL, marked by H₂S accumulation and a reduction in H₂S-consuming taxa (Faecalibacterium, Roseburia, Anaerostipes), a condition linked to proinflammatory metabolic processes⁴⁸. Network analysis consistently showed that alcohol-associated taxa, such as Parabacteroides and Bacteroides, formed mucin-degrading-dominant networks with weak connectivity to the mucin–SCFA module (Fig. 6). These contrasting network structures (Fig. 6) indicate that spicy food may support mucin homeostasis via mucin–SCFA coupling, whereas alcohol promotes mucin degradation under reduced SCFA flux through cross-feeding loss and H₂S activation^20,36,49. Furthermore, the negative correlation between TRPV1 and α-fucosidase gene families (GH29, GH95)—which were disconnected from the SCFA gene cluster—aligns with previous reports suggesting that TRPV1 activation indirectly promotes mucin synthesis^4,50. Collectively, these findings imply that the maintenance of mucin homeostasis by spicy food may serve as a determinant of resilience or disruption of gut metabolic health in the presence of alcohol exposure.

Nevertheless, the enrichment of Proteobacteria and Fusobacteriota taxa in the SCFA- and mucin-targeted gene families of the DHSH and DLSH groups (Fig. 5A, B) warrants cautious interpretation. Fusobacterium mortiferum, Escherichia coli, and Klebsiella pneumoniae are well-known dysbiosis-associated taxa that can induce epithelial injury via endotoxin production, and are linked to metabolic and inflammatory disorders^26,51,52. Genes such as galK (K00849) and galT (K00965) have been suggested to contribute indirectly to LPS biosynthesis^53,54, and incomplete reduction of H₂S-generating pathways (K00394, K00395, K00956, and K00957) by consumers in the human digestive tract may represent an additional risk factor^55,56. Notably, Proteobacteria are key constituents of mucin profile 3, reflecting disrupted mucin homeostasis⁴⁰.

In the DHSH group, the mucin- and SCFA-producing pathways were relatively upregulated (Fig. 5B). Although an appropriate level of mucin turnover can strengthen the protective barrier, excessive degradation has been reported to induce inflammatory injury, indicating the need for interpretation based on prior reviews⁴⁷. The amino acid metabolic pathways enriched in the DLSH group, including methionine, arginine, ornithine, and alanine metabolism (Fig. 4), may represent terminal metabolic routes associated with mucin degradation⁴⁰. However, hyperactivation of these pathways has also been linked to disturbances in host amino acid homeostasis, excessive production of H₂S and polyamines, and dysregulation of the serotonin–glucose axis, all of which may contribute to gut and metabolic diseases such as inflammatory bowel disease and insulin resistance^57,58. Furthermore, acetate-generating and stratified Klebsiella pneumoniae, a species associated with fatty liver risk, may reflect a metabolically inflammatory transitional state^59,60. These findings are consistent with previous reports that high concentrations of capsaicin can negatively impact the gut environment⁹; however, because this study did not include systematic quantification of capsaicin content in spicy foods, additional evidence is required. Nevertheless, given that the study population comprised healthy adults, epithelial injury markers showed alcohol-specific patterns, and inflammatory markers were detected at low levels, the spicy food intake observed here is likely within a range capable of maintaining mucin homeostasis. However, spicy food consumption may exert bidirectional modulation on mucus metabolism and microbial ecology, acting in either protective or detrimental directions, depending on consumption intensity.

This study had several limitations. The participants were healthy adults without clinical diseases; thus, I-FABP fluctuations should be interpreted as physiological variations rather than acute inflammatory responses. The cross-sectional design precludes causal inference, and classification based on consumption frequency rather than on quantitative intake limits the estimation of actual exposure. Additionally, because this was a remote study, blood and tissue analyses were not performed, and mechanistic interpretations related to mucin homeostasis relied on information in the literature rather than direct measurements. An imbalance in group sample sizes may also introduce statistical constraints; however, permutation-based tests and FDR corrections were applied to minimize potential bias. Future studies should incorporate quantitative dietary assessments and longitudinal designs to more clearly define the dose-response relationships between spicy food or alcohol intake and mucus layer function. With respect to spicy foods in particular, integrating quantitative intake data with refined assessments of individual sensitivity and sensory responses may reveal subtle physiological changes not captured by frequency-based classification alone. Moreover, integrated metabolomic and transcriptomic analyses using blood or tissue samples are required to directly verify whether the microbial functional changes observed in this study translate into epithelial injury signals or mucin regulatory pathways. Such approaches would provide a more precise understanding of the mechanisms by which dietary factors modulate gut barrier homeostasis.

With this study, we offer an analysis of the effects of alcohol and spicy food consumption on intestinal epithelial injury, gut microbial composition, and metabolic pathways in healthy adults. Alcohol intake was associated with elevated I-FABP levels, reflecting microepithelial injury, whereas spicy food intake promoted mucin metabolism and SCFA-linked compensatory pathways, supporting mucus layer stability. However, enriched amino acid metabolism in the DLSH group represents terminal mucin degradation processes that may predispose individuals to metabolic inflammation. In addition, the concurrent enrichment of Proteobacteria and Fusobacteriota in the DHSH group suggests a potential risk of dysbiosis through mucin degradation and endotoxin activation. Together, these findings suggest that spicy food exerts bidirectional regulation on gut mucus metabolism, maintaining mucin homeostasis at moderate levels but potentially aggravating mucus degradation and metabolic imbalance when combined with excessive alcohol exposure. Therefore, the intensity of spicy food intake and the level of alcohol exposure should be considered key determinants of mucin homeostasis and gut metabolic health.