Discussion

UC, an immune‐mediated intestinal inflammatory disease, has rapidly increasing incidence rates and has become a significant global public health concern. Multiple lines of evidence suggest that gut microbiota dysbiosis and the disruption of the intestinal mucosal barrier contribute to the occurrence and progression of UC (Cao et al. 2023; Gu et al. 2021). This study explored the collaborative effect of RB and the feruloyl esterase‐producing bacterium L. johnsonii 23 on DSS‐induced colitis in mice. We provide evidence that the simultaneous supplementation of RB and L. johnsonii 23 effectively ameliorates DSS‐induced colitis. This may be due to their synergistic action in releasing active substances from RB, exerting anti‐inflammatory and antioxidant effects, and improving colitis in mice.

Dietary and functional foods contain numerous functional active factors that serve as effective alternatives in the prevention and management of IBD (M. Li et al. 2022). RB is rich in various nutrients and possesses excellent health‐promoting functions and biological activities. In particular, ferulic acid possesses antioxidant and anti‐inflammatory properties. However, most ferulic acid in grains is bound to the cell wall through ester bonds, rendering it inaccessible to enzymatic degradation in the human digestive tract. Recent studies have shown that the fermentation of RB using microbial fungi or bacteria can produce extremely diverse metabolites and enhance its biological activity (Islam et al. 2021; Rusbana et al. 2020). Therefore, we hypothesized that the collaborative action of L. johnsonii 23 and RB could release active substances such as ferulic acid and oligosaccharides to alleviate intestinal inflammation, and we attempted to use L. johnsonii 23 and RB to mitigate colitis.

Body weight changes, DAI scores, colon length, and colon histopathological scores are crucial markers for evaluating the severity of UC (L. Li et al. 2023). DSS induction disrupts the systematic intestinal tissue structure, intestinal mucus barrier, and tight junctions between intestinal cells, leading to inflammatory cell infiltration (Gancarcikova et al. 2020). In this study, both individual and combined administration of RB and L. johnsonii 23 improved these UC markers. As expected, the combined application of RB and feruloyl esterase‐producing bacteria exhibited a superior effect in ameliorating UC.

Among immune regulatory factors, oxidative stress is considered a major mechanism promoting IBD development (Hwang et al. 2020). While moderate levels of reactive oxygen species (ROS) serve as second messengers regulating intracellular homeostasis and redox signaling, among other biological functions, to promote cell proliferation and tissue renewal, excessive ROS levels interact with DNA, proteins, and lipids, disrupting various metabolic and cellular homeostases, leading to cellular damage (Zuo et al. 2022). Furthermore, excessive ROS triggers abnormal activation of the intestinal immune system, weakens the mucus barrier, disrupts tight junctions, and reduces antimicrobial peptide secretion, further exacerbating UC progression (M. Li et al. 2022). Here, we found that individual administration of RB and L. johnsonii 23 increased the activity of key antioxidant enzymes in the colon of DSS‐induced mice. The RB group had a higher impact on SOD activity in UC mice, while the feruloyl esterase‐producing bacteria group showed a greater influence on CAT activity. The combined administration of RB and L. johnsonii 23 had the most significant impact on antioxidant enzyme activity, possibly due to the synergistic action between the two, leading to the release of free ferulic acid and oligosaccharides.

In UC, the persistent accumulation of inflammatory cells in the intestine is a crucial mechanism leading to inflammatory damage (Lee et al. 2018). Recognition of PAMPs associated with the intestinal microbiota and DAMPs related to oxidative stress activates the immune system to release a series of inflammatory mediators, attracting macrophages, neutrophils, and T lymphocytes into the intestine (Gong et al. 2019; Liston and Masters 2017). Subsequently, these inflammatory cells release inflammatory cytokines and ROS, leading to sustained damage to the intestinal mucosa and the expansion of the inflammatory response (Gilliland et al. 2023). In this study, DSS induction increased the levels of proinflammatory cytokines IL‐6, IL‐1β, and TNF‐α in the serum of mice, while anti‐inflammatory cytokine IL‐10 decreased. Individual intervention with RB and feruloyl esterase‐producing bacteria reversed this trend to varying degrees, with combined administration exhibiting a better anti‐inflammatory effect. Additionally, proinflammatory cytokines exacerbate intestinal inflammation by stimulating the activation of the NF‐κB signaling pathway (Shen et al. 2022). Signaling through this pathway is transmitted to IKKβ, leading to the phosphorylation of IκBα and the release of NF‐κB p65 into the nucleus, initiating or enhancing the transcription of genes related to inflammatory responses and apoptosis, ultimately promoting intestinal inflammation (Capece et al. 2022). Similarly, the combined administration of RB and L. johnsonii 23 showed stronger anti‐inflammatory capabilities. This may be partially attributed to the ability of feruloyl esterase to release free ferulic acid and oligosaccharides, exerting anti‐inflammatory and antioxidant effects.

SCFAs are a group of metabolites mainly produced by the fermentation of dietary fiber by intestinal microbiota. SCFAs play crucial roles in promoting immune cell function, energy metabolism, and intestinal homeostasis (Chen et al. 2023). Additionally, increased SCFAs levels in the cecum can lower the pH, inhibiting the growth and colonization of harmful bacteria (Guo et al. 2023). However, chronic UC leads to depletion of SCFAs in the cecal contents (Parada Venegas et al. 2019). In this study, compared to DSS‐induced model mice, combined intervention with RB and L. johnsonii 23 increased the levels of acetic acid, isobutyric acid, and butyric acid in the cecal contents of UC mice, with a superior effect compared to sulfasalazine treatment. This may be attributed to the utilization of a large amount of dietary fiber in RB by the intestinal microbiota for metabolism and SCFAs production. Additionally, L. johnsonii 23 produces feruloyl esterase that can break down dietary fiber, improving its utilization and increasing the production of SCFAs in the body. Notably, butyric acid, as an important SCFA, provides energy for colon cells and enhances the mucus barrier (Mohamed Elfadil et al. 2023). Therefore, these results suggest that the alleviation of UC by combined intervention with RB and L. johnsonii 23 is partially explained by modulation of the intestinal microbiota and its metabolites.

Compared with mainstream clinical UC treatments, the combined intervention of rice bran and L. johnsonii 23 shows distinct advantages and clear application positioning. Conventional chemical drugs (5‐ASA, glucocorticoids, immunosuppressants), biological monoclonal antibodies, and oral JAK inhibitors effectively relieve intestinal inflammation but are accompanied by obvious drawbacks including various systemic side effects, high treatment costs, infection risks, and drug resistance (Verstockt et al. 2023), while total colectomy permanently damages intestinal physiological function and reduces patients' quality of life (L. Li et al. 2023; Lu et al. 2026). As a natural synbiotic formula derived from agricultural by‐products and probiotics, this combination exerts synergistic antioxidant, anti‐inflammatory, and gut microbiota‐regulating effects via releasing free ferulic acid and elevating cecal SCFAs, with no detectable organ toxicity in mice and much lower economic cost. Nevertheless, it cannot replace pharmaceutical agents for severe acute UC flares; its core value lies in serving as a safe auxiliary dietary strategy to prevent UC onset and maintain remission for mild‐to‐moderate patients, which outperforms single rice bran or single strain supplementation due to the feruloyl esterase‐mediated synergistic activation of rice bran bioactive substances.