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Review

Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy

by
Lu Peng
1,
Long Wang
1,
Yingtong Zhao
2,
Peng Yu
3 and
Hongmei Yang
1,*
1
Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China
2
School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA
3
College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(22), 3591; https://doi.org/10.3390/nu17223591
Submission received: 14 October 2025 / Revised: 6 November 2025 / Accepted: 14 November 2025 / Published: 17 November 2025
(This article belongs to the Section Prebiotics and Probiotics)
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Abstract

The immune system plays a pivotal role in the progression of tumors. Recent advancements in immunotherapies, notably CAR-T cell therapy and checkpoint inhibitors, have markedly improved clinical outcomes. However, a significant proportion of patients continue to experience treatment resistance, posing a persistent and formidable challenge. The gut microbiota has been established as a critical determinant of responses to immunotherapy. Enriched with bioactive components such as polysaccharides, (poly)phenols, and flavonoids, edible and medicinal plants (EMPs) exhibit significant potential to enhance host immunity by reshaping the gut microbiota, increasing the production of microbiota-derived metabolites (e.g., short-chain fatty acids), strengthening the intestinal barrier, and reducing intestinal inflammation. The bioactive components derived from EMPs not only demonstrate substantial pharmacological activities but also serve dual roles: functioning either as inherent drug carriers or as effective modifiers for existing carrier systems, which facilitates targeted drug delivery to specific sites such as the liver and intestinal, enhancing therapeutic efficacy. In summary, this review highlights that bioactive components from EMPs hold significant promise for enhancing cancer immunotherapy by modulating complex interactions with the gut microbiota.

1. Introduction

Cancer poses a significant threat to human health, with GLOBOCAN 2022 data revealing approximately 20 million new cases and 9.7 million deaths globally with its mortality rate ranking second globally [1]. Traditional cancer treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, often lead to tumor recurrence and unfavorable prognosis. Immunotherapy targets immune cells and their interactions with tumor cells [2] and can treat metastatic malignant tumors and prolong the survival time of patients with good prognosis. However, due to the immunosuppressive tumor microenvironment (TME) and the immune escape mechanism of tumor cells, immunotherapy has limited efficacy in tumors [3]. At the same time, in the process of cancer immunotherapy, the emergence of drug resistance, immune-related adverse reactions and heterogeneity make immunotherapy face great clinical challenges.
The gastrointestinal tract contains 60–80% of the immune cells, which are crucial for maintaining intestinal homeostasis [4]. Research demonstrates that gut microbiota and metabolites not only modulate intestinal immunity but also exert influence on systemic cancer immunomodulation [4,5]. Recent studies show that the efficacy of cancer immunotherapy, encompassing immune checkpoint blockade (ICB), CAR-T cells, and cancer vaccines, varies significantly among individuals, which is related to the gut microbiome [6,7,8,9,10]. Therefore, gut microbiota represents a highly promising target for precision cancer immunotherapy.
Edible and medicinal plants (EMPs), as an indispensable and important part of traditional Chinese medicine, have functions of both nutritional and pharmacological. Due to high safety, minimal side effect, abundant functional components including polysaccharides, flavonoids, and saponins and multi-pathway pharmacological, EMPs display unique advantages in the field of cancer treatment, improving quality of life for patients [11]. Emerging evidence demonstrates that EMPs can modulate antitumor immune responses through gut microbiota regulation [12]. This interaction underscores the intricate interplay between active compounds de-rived from EMPs, the gut microbiome, and the cancer immune system. By delving into this crosstalk, researchers gain invaluable insights into the development of innovative immunotherapeutic strategies. Furthermore, the article examines current research advancements in utilizing active compounds from EMPs to engineer drug delivery systems for tumor therapy, offering translational insights for clinical applications.

2. Bioactive Compounds from EMPs and Regulation of Gut Microbiome

EMPs have been widely utilized in China, Korea, Japan, and other countries for treating various diseases, including cancer [13], inflammatory disorders [14], and neurodegenerative disease [15,16]. According to chemical structures, bioactive compounds from EMPs are categorized as polysaccharides, flavonoids, saponins, and (poly)phenols, alkaloids, terpenoid, phenolic compounds, coumarin, essential oil and volatile oil. Extensive research has shown that polysaccharides, saponins, and (poly)phenols found in MFH plants enhance anti-tumor immunity by directly or indirectly modulating immune cell activity and the gut microbiota [12,17,18,19] (Figure 1).

2.1. Polysaccharides

Polysaccharides are a class of natural bioactive compounds abundantly present in EMPs, including Astragalus membranaceus [20], Panax ginseng [21,22], and Lycium chinense [23,24], demonstrating unique anti-tumor activities. Increasing evidence demonstrates that polysaccharides play a crucial role in maintaining gut microbial homeostasis by regulating both the structural composition and metabolic activities of the gut flora, preserving intestinal barrier integrity, and ultimately enhancing gut immunity [25,26]. Ginseng polysaccharides (GPs), bioactive components of Panax ginseng, enhanced PD-1 blockade therapy by modulating gut microbial metabolism and composition, which collectively increased CD8+ T cell recruitment while inhibiting Treg-mediated immunosuppression. Furthermore, GPs promote the abundance of Parabacteroides distasonis and Bacteroides vulgatus, bacterial genera crucial for ginsenoside biotransformation, which was significantly associated with therapeutic response and prognosis. Clinical investigations have demonstrated that GPs improves therapeutic response to PD-1 checkpoint blockade, potentially overcoming immunotherapy resistance [27]. The water-soluble polysaccharides extracted from the spore bodies of Ganoderma lucidum polysaccharides (GLP) inhibit the TLR4/MyD88/NF-κB signaling pathway, improving the microbial flora imbalance induced by AOM/DSS, increasing the production of short-chain fatty acids, and alleviating endotoxemia. In addition, GLP can significantly improve the intestinal barrier function, inhibit the infiltration of macrophages, and suppress colonic inflammation and tumor occurrence [22]. In addition, emerging research indicates that polysaccharides such as Lycium barbarum polysaccharides [28], Lentinula edodes polysaccharides [29,30] and Astragalus polysaccharides (APS) [31] modulate gut microbiota and their derived metabolites, promoting the restoration of immune function. These findings demonstrate that polysaccharides can serve as adjuvants to improve intestinal and immunosuppression.

2.2. (Poly)Phenols

(Poly)phenols, renowned for their robust antioxidant and anti-inflammatory benefits, are one of the most important and widely occurring bioactive components in EMPs. Flavonoids, phenolic acids, lignans, and stilbenes are the four main types of (poly)phenols [32]. Among these, flavonoids are the most abundant, followed by phenolic acids.
Flavonoids exhibit diverse biological activities and pharmacological effects. Their diverse structures, including isoflavones, neoflavonoids, flavones, flavonols, flavanones, flavanonols, flavanols, and chalcones, endow them with potent antioxidant, anti-inflammatory, and anti-tumor properties [33]. Accumulating research suggests that flavonoids extracted from EMPs, such as kaempferol (a flavonol) and calycosin (an isoflavone from Astragalus membranaceus), can enhance cancer immunotherapy by activating antitumor immune responses through remodeling the gut microbial diversity and modulating microbial metabolites [34,35,36]. Inflammatory bowel disease (IBD) is a persistent and debilitating condition characterized by chronic intestinal inflammation with the potential to progress to colorectal cancer (CRC) [37]. Luteolin, a bioactive flavonoid derived from EMPs such as honeysuckle (Lonicera japonica), astragalus (Astragalus membranaceus), and angelica (Angelica sinensis), demonstrates significant therapeutic effects against IBD [38,39]. Its mechanisms of action include: (1) modulating T-cell subset differentiation [40], (2) downregulating pro-inflammatory mediators, (3) activating antioxidant pathways [41,42], (4) enhancing gut microbiota composition [43,44], and (5) restoring intestinal mucosal barrier function through specific molecular signaling pathways [45]. These multifaceted actions collectively ameliorate IBD symptoms and consequently suppress CRC development. However, the majority of (poly)phenols that escape gastrointestinal absorption reach the colon directly, and are metabolized by gut microbes into a spectrum of smaller phenolic acids. These metabolites exhibit greater biological activity and higher absorption efficiency. For example, ellagic acid is converted into urolithins, which significantly enhance gut barrier function, reduce inflammation, and create a systemically favorable environment for antitumor immunity [46]. Furthermore, resveratrol, a natural stilbenes compound enhances antitumor immune responses by modulating the abundance and composition of intestinal microbiota, ultimately enhancing the outcome of cancer immunotherapy [47].
Additionally, other polyphenolic compounds such as curcumin can remodel the gut microbiota composition by enriching beneficial bacteria, which are closely associated with the maintenance of intestinal barrier integrity, anti-inflammatory effects, the production of beneficial metabolites and tumor microenvironment remodeling [48,49,50].

2.3. Saponins

Saponins are a constitute a diverse class of bioactive compounds ubiquitously present in EMPs. These structurally complex phytochemicals exhibit diverse biological activities attributable to their intricate chemical architectures, including immunomodulation [51,52], cardiovascular protection [53,54], antioxidant effects [55,56], and antitumor properties [57,58,59]. Based on their aglycone structures, saponin family, two primary categories can be distinguished: triterpenoid saponins (such as ginseng, licorice, astragalus, and platycodon) and steroidal saponins (like ophiopogon japonicus and Chinese yam). Among these, triterpenoid saponins are particularly notable for their immunomodulatory and antitumor activities, such as ginsenoside and astragaloside. Emerging evidence suggests that multiple ginsenosides (such as Rh2 [60], Rg1 [61] and Rk3 [62]) regulate gut microbial diversity and promote anti-tumor immune responses, inhibiting tumor growth. Rk3, in particular, has demonstrated remarkable potential in ameliorating gut microbi-ota dysbiosis by promoting the enrichment of beneficial bacteria like Akkermansia muciniphila and Barnesiella intestinihominis. And eliminating pathogenic Desulfovibrio species, Rk3 restores intestinal barrier integrity. Mechanistically, Rk3 modulates chemokine and inflammatory cytokine production through regulation of innate lymphoid cells and T helper 17 (Th17) cell signaling pathways, significantly suppressing colonic tumorigenesis [62]. Moreover, recent studies revealed that Astragaloside IV(AS-IV) exhibits potent immunomodulatory and gastrointestinal protective effects by alleviating mucosal inflammation and restoring intestinal barrier integrity during different stages of IBD progression to colorectal cancer. AS-IV exerts their therapeutic effects through multiple mechanisms, including targeting key immune signaling pathways (like NF-κB and PPAR) and promoting M1 macrophage polarization, suppressing tumor growth and metastasis via multi-targeted actions, which offers novel strategies for future drug development [63].

3. Synergistic Effects of the Bioactive Compounds from EMPs on Immunotherapy via Gut Microbiota Modulation

To counteract tumor immune evasion during cancer progression, various immunotherapies have been developed [2]. However, tumor immunotherapy faces substantial limitations and challenges. Immune checkpoint blockade therapies, notably PD-1 and PD-L1 blockers, demonstrate clinical efficacy in only approximately <30% of patients, with a subset of responders eventually experiencing disease recurrence [64]. Meanwhile, chimeric antigen receptor (CAR) T-cell therapy exhibits limited therapeutic potential against solid tumors [65]. Furthermore, immunotherapeutic interventions are often accompanied by severe immune-related adverse events and can lead to the development of treatment resistance. Recent preclinical and clinical studies have brought the gut microbiota into the spotlight, revealing its pivotal role in modulating the patient’s response to immunotherapy [8,66,67]. Research indicates that the gut microbiome-derived metabolites and secreted molecules enhance immunotherapy efficacy [68,69]. With advantages including natural derivation, multi-target modulation, and low toxicity, bioactive compounds from EMPs can synergize with immunotherapy by modulating gut microbiota, which reduces treatment toxicity while improving antitumor efficacy, leading to better patient outcomes. Emerging research reveals that active ingredients from medicinal foods potentiate cancer immunotherapy via modulating gut microbiota composition, promoting the production of beneficial metabolites such as short-chain fatty acids (SCFAs) (Figure 2), and improving intestinal barrier function to reduce inflammation (Figure 3).

3.1. Restructuring of the Gut Microbiome

Emerging evidence suggests that specific gut bacteria, notably Bacteroides fragilis, Bacteroides thetaiotaomicron, Bifidobacterium species, Akkermansia muciniphila, and Faecalibacterium spp., may improve the outcome of cancer immunotherapy, as observed in preclinical studies and patient cohorts [8,9,70,71]. Consequently, therapeutic strategies targeting gut microbiota modulation have been proposed to enhance treatment efficacy in oncology. Among immunotherapeutic approaches, immune checkpoint inhibitors (ICIs) constitute the most extensively studied class of immunotherapeutic agents [72,73,74]. However, their low response rates in cancer patients remain a major therapeutic challenge.
As the dominant effector population in anti-tumor immunity, CD8+ T cells have shown remarkable therapeutic efficacy in various immunotherapeutic strategies. Anti-PD-1 antibodies blockade activated CD8+ T cells to secrete perforin and granzyme B, mediating tumor cell death [75,76]. Modulation of the microbiota-immune axis by bioactive compounds from EMPs represents a key mechanism for improving ICI efficacy. GPs, for instance, enhance immune surveillance. They achieve this by elevating Lachnospiraceae abundance, an effect that suppresses myeloid-derived suppressor cells (MDSCs) and subsequently facilitates the infiltration and activation of CD8+ T cells [77,78]. When combined with αPD-1 monoclonal antibody (mAb) therapy, GPs demonstrate an additional layer of benefit. They reshape the gut microbiota profile, leading to improved sensitivity to anti-PD-1 immunotherapy in patients with non-small cell lung cancer (NSCLC) [27]. In addition, recent research showed that Chinese yam polysaccharide (CYPs), derived from medicinal food plants, exhibit immunomodulatory and antitumor properties. 16S rRNA sequencing revealed that combined treatment with CYPs and αPD-1 monoclonal antibody (mAb) enriched beneficial bacteria (e.g., *Clostridium_UCG-014* and Actino-bacteria), while simultaneously reducing the abundance of pathogenic bacteria including Enterobacteriaceae and Desulfovibrionaceae. This shift in gut microbiota composition was accompanied by modifications within the tumor microenvironment (TME). Specifically, the combination therapy suppressed immunosuppressive M2 macrophages (CD206+ subset) and enhanced the infiltration of cytotoxic CD8+ T cells. Consequently, patients with colorectal cancer (CRC) exhibited an improved response to anti-PD-1 immunotherapy [79]. Bilberry anthocyanin extracts enhanced the efficacy of ICIs by elevating the relative abundance of Clostridia and Lactobacillus johnsonii and increasing overall microbial community diversity [80].
Based on the aforementioned findings, we conclude that bioactive components de-rived from EMPs enhance the efficacy of tumor immunotherapy through dual mechanisms: on one hand, by modulating the composition of the gut microbiota (promoting the proliferation of beneficial bacteria and inhibiting the growth of harmful ones), and on the other hand, by regulating the immunosuppressive tumor microenvironment. This discovery opens new avenues for microbiota-targeted cancer therapy, fully demonstrating the application potential of EMPs bioactive in the field of immune regulation.

3.2. Microbial Metabolites

Metabolites derived from gut microbiota reshape the tumor microenvironment [81,82,83]. These metabolites boost the efficacy of immunotherapy by activating the immune response, effectively eliminating tumor cells, and overcoming drug resistance. Furthermore, they alleviate severe treatment-related side effects [84]. Therefore, targeting gut microbiota-derived metabolites represents a promising therapeutic strategy to enhance tumor immunotherapy response rates in patients.
Research indicates that non-digestible bioactive compounds (e.g., polysaccharides) derived from EMPs are metabolized by specific gut bacteria, such as Bifidobacterium and Lactobacillus, which subsequently ferment them into short-chain fatty acids (SCFAs), including propionate and butyrate [85,86,87]. SCFAs regulate immune cells function to augment antitumor immune responses and maintain intestinal homeostasis through mechanisms involving the activation of G-protein-coupled receptors (GPRs) and inhibition of histone deacetylases (HDAC) [88,89,90,91]. In addition, (poly)phenols-EMPs components, such as pomegranate ellagitannins, are metabolized by gut microbiota into ellagic acid and further converted into urolithins that can reshape the gut microbiota and modulate the tumor microenvironment. Moreover, when combined with anti-PD-1 antibody therapy, they have been shown to inhibit the growth of colon cancer, thereby supporting more effective anticancer treatment [92,93]. Together, these findings reveal how interactions between gut microbiota and EMPs may offer novel strategies for developing natural adjuvants to enhance cancer immunotherapy.

3.3. Intestinal Barrier Dysfunction and Intestinal Inflammation

Cancer immunotherapy, particularly ICIs, commonly triggers immune-related adverse events (irAEs). Many of these irAEs are closely associated with gut microbiota dysbiosis and impaired intestinal barrier function. This impairment, characterized by mucosal injury and increased permeability, facilitates bacterial translocation and sys-temic inflammation [94,95,96,97]. A healthy gut microbiome and an intact intestinal barrier are fundamental to immune homeostasis [98,99]. Their disruption can initiate systemic chronic inflammation, thereby promoting the expansion of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Consequently, an immunosuppressive tumor microenvironment (TME) is created, which can result in either primary or acquired resistance to ICIs [100,101,102]. Therefore, targeting the intestinal barrier and inflammation represents a viable strategy for sensitizing tumors to immunotherapy.
The intestinal barrier functions as a vital line of defense, shielding the body from harmful external pathogens and toxins [103]. It is well established that numerous components from EMPs directly or indirectly contribute to the intestinal barrier integrity [104,105,106]. Polysaccharides, known for their favorable safety profile, are effective in reducing inflammation and suppressing the growth of malignant tumors, which represent a promising adjuvant therapy for a variety of disorders associated with intestinal barrier injury [105]. Numerous bioactive polysaccharides, including those derived from Plantago asiatica [107], Lycium barbarum [108] and Spirulina [109] have been shown to modulate the expression of tight junction proteins (including occludin, claudin-1, ZO-1, and ZO-3), which collectively contribute to the amelioration of epithelial barrier dysfunction.
Additionally, studies indicate that approximately 60% of cancer patients treated with ICIs develop severe treatment-limiting toxicities [110,111], these toxicities are closely linked to inflammation-related adverse events triggered by the treatment [112,113,114]. Colitis is a common and severe adverse effect of ICIs therapy. Therefore, developing targeted therapeutic strategies for intestinal inflammation—aimed at effectively managing toxicity while preserving or even enhancing the antitumor efficacy of ICIs—represents a promising approach. As potent natural anti-inflammatory agents, various bioactive compounds from EMPs serve such as astragalosides [115], curcumin [116,117], ginsenoside Rh2 [118], Alpinia officinarum Hance polysaccharides [119], and Portulaca oleracea L. (poly)phenols [120], work synergistically through multiple targets and pathways, precisely modulating key signaling pathways associated with intestinal inflammation, including PI3K/AKT, NF-κB, MAPK, and JAK/STAT—thereby effectively alleviating gut barrier disruption and reducing intestinal inflammation. Clinical studies have also shown that certain medicinal food homologous ingredients, such as curcumin, can serve as an adjunctive therapy to significantly improve the clinical remission rate and endoscopic improvement scores in patients with ulcerative colitis [121].
Based on these findings, it has been elucidated that natural bioactive compounds from EMPs can enhance tumor immunotherapy by modulating the gut microbiota composition, regulating microbial metabolites, improving intestinal barrier dysfunction, and alleviating intestinal inflammation, which work synergistically to mitigate adverse effects induced by immunotherapy, increase patient response rates, and improve overall treatment efficacy.

4. Construct DDS Based on Components from EMPs

EMPs compounds including polysaccharides, (poly)phenols, flavonoids, and saponins, demonstrate considerable promise in bolstering tumor immunotherapy by orchestrating the intricate dance between gut microbiota and the immune system. Nevertheless, the journey from lab to clinic for these bioactive compounds is fraught with obstacles, primarily stemming from their inherently low bioavailability. This challenge arises due to their poor water solubility, chemical instability, and inefficient intestinal absorption, which significantly hamper their therapeutic potential. Recent studies have confirmed that advanced drug delivery systems (DDS) strategies, such as nanotechnology, targeted delivery systems, and biotransformation, can significantly enhance the anti-tumor efficacy of EMPs bioactive compounds [122,123,124]. These approaches not only reduce side effects and improve patient compliance but also hold great promise for developing these compounds into effective adjuvant interventions for tumor immunotherapy. However, DDS still faces numerous challenges and problems. EMPs components are now being extensively explored as “smart materials” for constructing or functionalizing drug delivery systems (DDS), rather than merely serving as the encapsulated “cargo,” owing to their inherent bioactivity, excellent biocompatibility, and unique physicochemical properties [125,126]. Additionally, their ability to modulate immune cell function enables an integrated strategy of “delivery and therapy in one.

4.1. Advantages of Bioactive Compounds from EMPs for DDS Carriers

An ideal DDS should be capable of precisely delivering drugs to the diseased site. Nevertheless, Dai et al. revealed that due to target heterogeneity, the delivery efficiency of nanoparticles to cancer cells is abysmally low, with only approximately 0.0014% of the ligand-modified nanoparticles successfully binding to them [127]. Natural plant active ingredients such as polysaccharides possess inherent targeting capabilities that can be further optimized through functionalization. By constructing novel DDS using these natural components, it’s possible to significantly improve drug accumulation at the site of disease. For example, Liu et al. developed a novel nanocarrier material, AA/ASP-AZO-Fc, by leveraging the intrinsic liver-targeting property of Angelica sinensis polysaccharide (ASP). The resulting polymeric micelle system effectively delivered curcumin to hepatic tissues, demonstrating a targeted therapeutic strategy for hepatocellular carcinoma in Figure 4 [128]. Furthermore, nanotechnology can be integrated with immunotherapy to enhance tumor-targeted treatment [129]. Liu et al. designed novel methotrexate (MTX)-modified PPT nanoparticles loaded with Astragalus polysaccharide micelles. This system can safely and effectively target ovarian cancer cells and achieve precise drug release. Additionally, it exerts immunomodulatory effects on tumor-associated macrophages to combat tumor cells, thereby enhancing the efficacy of immunotherapy for ovarian cancer [130] (Figure 4).
Indeed, the long-term biosafety of numerous nanocarrier materials is still not fully understood, posing significant concerns for their widespread use in medical applications. Nel and his colleagues emphasized that the inherent characteristics of nano-materials can have adverse impacts, primarily through detrimental interactions with both biological systems and the environment, potentially leading to toxicity [131]. Among these nanomaterials, liposomes have been prominently used as carriers in drug delivery systems. With various formulations available, they have entered clinical applications for targeted cancer therapy [132,133]. However, despite their success, clinical studies have unveiled a crucial dilemma with liposomes: they often exhibit low targeting efficiency and increased systemic toxicity, resulting in unwanted side effects for patients [134,135,136,137]. Natural biopolymers are recognized for their established safety profile, excellent biodegradability, non-toxic degradation products and favorable tolerability, make them promising candidates for replacing synthetic materials in DDS [126,138]. The enhancement of the physicochemical properties of DDS by bioactive compounds such as ginsenosides can increase the bioavailability of active pharmaceutical ingredients, potentiating their antitumor therapeutic effects [126,139]. For instance, ginsenoside Rh2-liposomes can replace cholesterol, significantly prolonging their circulation time in vivo. Their key advantages include active targeting of tumor cells, increased drug accumulation at tumor sites, and effective remodeling of the TME to reverse immunosuppression, potently inhibiting tumor growth [140]. Bioactive food-derived components serving as DDS carriers offer a multifunctional and innovative platform for anticancer drug delivery.

4.2. Intestinal-Targeting Release of the Medication

Oral administration remains the most favored method for drug delivery, primarily due to its unparalleled convenience and high patient compliance [141]. However, the highly acidic environment of gastric acid can lead to its inactivation, degradation by gastrointestinal enzymes may reduce its bioavailability, and its premature release in non-target areas could potentially cause systemic side effects [142]. In order to achieve efficient and precise delivery of these active ingredients to specific intestinal sites and control their release behavior, researchers have turned their attention to colon-targeted drug delivery systems. These systems are particularly crucial for the treatment of IBD and colon cancer. They also play a vital role in enhancing the bioavailability of drugs that are prone to degradation, thereby facilitating their systemic absorption [143,144]. Delivery systems utilizing edible bioactive compounds which offer excellent biocompatibility, biodegradability, low toxicity, and ease of functional modification have emerged as ideal carriers for colon-targeted drug delivery [144]. Edible bioactive ingredients exhibit diverse responsive properties, allowing them to be naturally engineered to respond to specific intestinal conditions such as pH and microbial enzymes, enabling targeted drug release at disease sites. Natural polysaccharides are widely used in oral colon-targeted drug delivery systems owing to their high safety, structural diversity, and unique property of being degraded specifically by enzymes produced by the colonic microbiota. This enzymatic reliance enables precise drug release in the colon [145]. Furthermore, leveraging the pH sensitivity of polysaccharides, nanoscale polysaccharide-based carriers can be used to construct responsive delivery systems. This property enables targeted drug release in the intestinal tract and allows for controlled therapeutic delivery [146] (Figure 4). Moreover, orally administered nano-drugs derived from EMPs bioactive components can reach the systemic circulation through colonic absorption. Their antitumor efficacy is then achieved through two primary mechanisms: the direct elimination of tumor cells and the modulation of the gut microbiota [147]. Based on EMPs compounds, natural, safe, and robust delivery systems are expected to lead the field of oral drug delivery into a new era characterized by sustainability, precision, and personalization, thereby offering innovative solutions for nutritional intervention and disease treatment.

5. Conclusions and Future Perspectives

In recent years, cancer immunotherapy, particularly ICBs, has become a hotspot in cancer treatment. However, during immunotherapy, due to tumor heterogeneity and inter-patient variability, irAEs might arise, including issues such as drug resistance and poor prognosis. Gut microbiota and their metabolites can modulate tumor immune responses. In turn, cancer can reshape the gut microbial composition, leading to the modulation of TME and the promotion of immune suppression [148]. This review has detailed that EMPs, which are abundant in polysaccharides, (poly)phenols, and saponins (exemplified by traditional sources like ginseng, astragalus, angelica, and turmeric), exhibit favorable characteristics: high safety, stability, low toxicity, and multi-targeting capability. Notably, EMPs can enhance anti-tumor immune responses and synergize with cancer immunotherapy via bidirectional interactions with the gut microbiota, constituting a highly promising interdisciplinary research field. Beyond their direct use as anti-cancer agents, the bioactive compounds of EMPs can also participate in the assembly of drug delivery systems, which enables targeted transport of therapeutic agents to specific sites, facilitating precise cancer treatment. Additionally, DDS assembled from EMPs compounds offer a promising alternative to synthetic materials, mitigating the long-term toxicity concerns associated with their use, while also boosting the bioavailability and anti-tumor potency of the therapeutic agents.
Nevertheless, substantial challenges persist in effectively translating these findings into clinical practice. The inherent variability in the origin, processing, and extraction of EMPs leads to significant inconsistencies in the composition and concentration of their bioactive compounds, resulting in poor reproducibility and unstable research outcomes. This complexity is compounded by the fact that, unlike single-compound drugs, their extracts are multi-component mixtures, making it difficult to determine whether their overall interaction with cancer immunotherapy is synergistic or antagonistic. The translation of bioactive components from EMPs into therapeutic applications faces significant challenges, primarily due to their low solubility, chemical instability, and inefficient absorption. To address these issues, complex delivery systems are necessary. However, individual patient factors, including diet, genetics, and gut microbiome composition, introduce high variability, potentially complicating the outcomes of microbiota-targeted interventions using EMPs bioactive components. Despite the promise of many nano-delivery systems assembled from EMPs bioactive components, their long-term safety, targeting accuracy, and toxicological profile require thorough evaluation. Taken together, these advancements underscore the substantial potential of leveraging the interplay between bioactive components from EMPs and the gut microbiota to enhance the efficacy of cancer immunotherapy.
The bioactive components derived from EMPs offer a promising avenue for enhancing cancer immunotherapy. When combined with traditional treatments like chemotherapy, radiotherapy, and targeted therapy, these components have the potential to mitigate adverse side effects and boost therapeutic outcomes. While preliminary preclinical and small-scale clinical studies have shown encouraging results, further research is imperative. Conducting rigorous clinical trials is crucial to thoroughly assess the safety and effectiveness of these EMPs bioactive components in cancer immunotherapy. Additionally, elucidating the mechanisms of action and comparing their effectiveness with existing treatments will be vital for developing safer, more effective, and personalized cancer therapies. In summary, while the potential of EMPs bioactive constituents in cancer immunotherapy is significant, future research must focus on comprehensive clinical trials, mechanistic elucidation, and comparative effectiveness studies.

Author Contributions

Conceptualization: L.P. and H.Y.; literature search: L.P.; writing—original draft preparation: L.P.; writing—review and editing: H.Y., L.W. and Y.Z.; supervision: H.Y. and P.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This review was financially supported by the Science and Technology Development Planning Project of Jilin Province (no. 20240305022YY) and Changchun Talents Technology Innovation Project (no. 2025ccyc01).

Data Availability Statement

No new data were created or analyzed in this study.

Acknowledgments

During the preparation of this review, the authors used https://www.biorender.com (accessed on 9 October 2025) for the purposes of creating figures. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA A Cancer J. Clin. 2023, 73, 17–48. [Google Scholar] [CrossRef]
  2. Chen, D.S.; Mellman, I. Oncology meets immunology: The cancer-immunity cycle. Immunity 2013, 39, 1–10. [Google Scholar] [CrossRef]
  3. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed]
  4. McDermott, A.J.; Huffnagle, G.B. The microbiome and regulation of mucosal immunity. Immunology 2014, 142, 24–31. [Google Scholar] [CrossRef]
  5. Wong, S.H.; Yu, J. Gut microbiota in colorectal cancer: Mechanisms of action and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 690–704. [Google Scholar] [CrossRef]
  6. Asokan, S.; Cullin, N.; Stein-Thoeringer, C.K.; Elinav, E. CAR-T Cell Therapy and the Gut Microbiota. Cancers 2023, 15, 794. [Google Scholar] [CrossRef]
  7. Frankel, A.E.; Coughlin, L.A.; Kim, J.; Froehlich, T.W.; Xie, Y.; Frenkel, E.P.; Koh, A.Y. Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients. Neoplasia 2017, 19, 848–855. [Google Scholar] [CrossRef] [PubMed]
  8. Vétizou, M.; Pitt, J.M.; Daillère, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P.; et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015, 350, 1079–1084. [Google Scholar] [CrossRef] [PubMed]
  9. Routy, B.; Gopalakrishnan, V.; Daillère, R.; Zitvogel, L.; Wargo, J.A.; Kroemer, G. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 2018, 15, 382–396. [Google Scholar] [CrossRef]
  10. Jing, N.; Wang, L.; Zhuang, H.; Jiang, G.; Liu, Z. Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder. Front. Immunol. 2023, 14, 1195075. [Google Scholar] [CrossRef]
  11. Tan, W.; Pan, T.; Wang, S.; Li, P.; Men, Y.; Tan, R.; Zhong, Z.; Wang, Y. Immunometabolism modulation, a new trick of edible and medicinal plants in cancer treatment. Food Chem. 2022, 376, 131860. [Google Scholar] [CrossRef] [PubMed]
  12. Xia, L.; Li, C.; Zhao, J.; Sun, Q.; Mao, X. Rebalancing immune homeostasis in combating disease: The impact of medicine food homology plants and gut microbiome. Phytomedicine 2025, 136, 156150. [Google Scholar] [CrossRef]
  13. Zhou, Z.; Nan, Y.; Li, X.; Ma, P.; Du, Y.; Chen, G.; Ning, N.; Huang, S.; Gu, Q.; Li, W.; et al. Hawthorn with “homology of medicine and food”: A review of anticancer effects and mechanisms. Front. Pharmacol. 2024, 15, 1384189. [Google Scholar] [CrossRef]
  14. Lu, Q.; Li, R.; Yang, Y.; Zhang, Y.; Zhao, Q.; Li, J. Ingredients with anti-inflammatory effect from medicine food homology plants. Food Chem. 2022, 368, 130610. [Google Scholar] [CrossRef]
  15. Wen, S.; Han, Y.; Li, Y.; Zhan, D. Therapeutic Mechanisms of Medicine Food Homology Plants in Alzheimer’s Disease: Insights from Network Pharmacology, Machine Learning, and Molecular Docking. Int. J. Mol. Sci. 2025, 26, 2121. [Google Scholar] [CrossRef]
  16. Li, M.J.; Xu, J.Y.; Zhang, H.Y.; Guo, M.; Lan, M.N.; Kong, J.; Liu, S.W.; Zheng, H.J. A medicine and food homology formula prevents cognitive deficits by inhibiting neuroinflammation and oxidative stress via activating AEA-Trpv1-Nrf2 pathway. Inflammopharmacology 2024, 32, 3745–3759. [Google Scholar] [CrossRef]
  17. Zhao, L.; Xu, C.; Zhou, W.; Li, Y.; Xie, Y.; Hu, H.; Wang, Z. Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications. J. Ethnopharmacol. 2023, 309, 116296. [Google Scholar] [CrossRef]
  18. Pan, J.; Wang, H.; Chen, Y. Prunella vulgaris L.—A Review of its Ethnopharmacology, Phytochemistry, Quality Control and Pharmacological Effects. Front. Pharmacol. 2022, 13, 903171. [Google Scholar] [CrossRef]
  19. Liu, C.; He, P.; Qiao, R.; Yang, X.; Ding, C.; He, F. Mechanistic study of Lonicerae Japonicae Flos (Caprifoliaceae) in non-small cell lung cancer prevention and treatment through integrative pharmacology, multi-machine learning, artificial intelligence, and in vitro experiments. J. Ethnopharmacol. 2025, 348, 119832. [Google Scholar] [CrossRef] [PubMed]
  20. Xu, Q.; Cheng, W.; Wei, J.; Ou, Y.; Xiao, X.; Jia, Y. Synergist for antitumor therapy: Astragalus polysaccharides acting on immune microenvironment. Discov. Oncol. 2023, 14, 179. [Google Scholar] [CrossRef] [PubMed]
  21. Lee, J.S.; Lee, H.Y. Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells. J. Ginseng Res. 2024, 48, 266–275. [Google Scholar] [CrossRef]
  22. Guo, C.; Guo, D.; Fang, L.; Sang, T.; Wu, J.; Guo, C.; Wang, Y.; Wang, Y.; Chen, C.; Chen, J.; et al. Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon. Carbohydr. Polym. 2021, 27, 118231. [Google Scholar] [CrossRef]
  23. Cheng, J.; Zhou, Z.W.; Sheng, H.P.; He, L.J.; Fan, X.W.; He, Z.X.; Sun, T.; Zhang, X.; Zhao, R.J.; Gu, L.; et al. An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides. Drug Des. Devel. Ther. 2015, 9, 33–78. [Google Scholar] [CrossRef]
  24. Tian, X.; Liang, T.; Liu, Y.; Ding, G.; Zhang, F.; Ma, Z. Extraction, Structural Characterization, and Biological Functions of Lycium Barbarum Polysaccharides: A Review. Biomolecules 2019, 9, 389. [Google Scholar] [CrossRef]
  25. Guo, H.; Gibson, S.A.; Ting, J.P.Y. Gut microbiota, NLR proteins, and intestinal homeostasis. J. Exp. Med. 2020, 217, e20181832. [Google Scholar] [CrossRef] [PubMed]
  26. Ahmadi, S.; Mainali, R.; Nagpal, R.; Sheikh-Zeinoddin, M.; Soleimanian-Zad, S.; Wang, S.; Deep, G.; Kumar Mishra, S.; Yadav, H. Dietary Polysaccharides in the Amelioration of Gut Microbiome Dysbiosis and Metabolic Diseases. Obes. Control Ther. Open Access. 2017, 4, 1–15. [Google Scholar] [CrossRef]
  27. Huang, J.; Liu, D.; Wang, Y.; Liu, L.; Li, J.; Yuan, J.; Jiang, Z.; Jiang, Z.; Hsiao, W.W.; Liu, H.; et al. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy. Gut 2022, 71, 734–745. [Google Scholar] [CrossRef] [PubMed]
  28. Cao, C.; Wang, Z.; Gong, G.; Huang, W.; Huang, L.; Song, S.; Zhu, B. Effects of Lycium barbarum Polysaccharides on Immunity and Metabolic Syndrome Associated with the Modulation of Gut Microbiota: A Review. Foods 2022, 11, 3177. [Google Scholar] [CrossRef]
  29. Jin, X.; Wu, Z.; Chen, H.; Liu, W.; Gu, F.; Li, J. Extraction and Identification of Polysaccharide from Lentinus edodes and Its Effect on Immunosuppression and Intestinal Barrier Injury Induced by Cyclophosphamide. Int. J. Mol. Sci. 2024, 25, 12432. [Google Scholar] [CrossRef]
  30. Morales, D.; Shetty, S.A.; López-Plaza, B.; Gómez-Candela, C.; Smidt, H.; Marín, F.R.; Soler-Rivas, C. Modulation of hu-man intestinal microbiota in a clinical trial by consumption of a β-d-glucan-enriched extract obtained from Lentinula edodes. Eur. J. Nutr. 2021, 60, 3249–3265. [Google Scholar] [CrossRef]
  31. Wang, H.; Zhu, W.; Hong, Y.; Wei, W.; Zheng, N.; He, X.; Bao, Y.; Gao, X.; Huang, W.; Sheng, L.; et al. Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism. Phytomedicine 2024, 128, 155492. [Google Scholar] [CrossRef] [PubMed]
  32. Zhou, Y.; Zheng, J.; Li, Y.; Xu, D.P.; Li, S.; Chen, Y.M.; Li, H.B. Natural Polyphenols for Prevention and Treatment of Cancer. Nutrients 2016, 8, 515. [Google Scholar] [CrossRef]
  33. Roy, A.; Khan, A.; Ahmad, I.; Alghamdi, S.; Rajab, B.S.; Babalghith, A.O.; Alshahrani, M.Y.; Islam, S.; Islam, M.R. Flavonoids a Bioactive Compound from Medicinal Plants and Its Therapeutic Applications. Biomed Res. Int. 2022, 2022, 5445291. [Google Scholar] [CrossRef]
  34. Guan, M.; Xu, W.; Bai, H.; Geng, Z.; Yu, Z.; Li, H.; Liu, T. Potential mechanisms underlying inhibition of xenograft lung cancer models by kaempferol: Modulation of gut microbiota in activating immune cell function. J. Cancer 2024, 15, 1314–1327. [Google Scholar] [CrossRef]
  35. Bratkov, V.M.; Shkondrov, A.M.; Zdraveva, P.K.; Krasteva, I.N. Flavonoids from the Genus Astragalus: Phytochemistry and Biological Activity. Pharmacogn. Rev. 2016, 10, 11–32. [Google Scholar] [CrossRef]
  36. Che, Y.; Li, L.; Kong, M.; Geng, Y.; Wang, D.; Li, B.; Deng, L.; Chen, G.; Wang, J. Dietary supplementation of Astragalus flavonoids regulates intestinal immunology and the gut microbiota to improve growth performance and intestinal health in weaned piglets. Front. Immunol. 2024, 15, 1459342. [Google Scholar] [CrossRef]
  37. Hirsch, D.; Hardt, J.; Sauer, C.; Heselmeyer-Hadded, K.; Witt, S.H.; Kienle, P.; Ried, T.; Gaiser, T. Molecular characterization of ulcerative colitis-associated colorectal carcinomas. Mod. Pathol. 2021, 34, 1153–1166. [Google Scholar] [CrossRef]
  38. Imran, M.; Rauf, A.; Abu-Izneid, T.; Nadeem, M.; Shariati, M.A.; Khan, I.A.; Imran, A.; Erdogan Orhan, I.; Rizwan, M.; Atif, M.; et al. Corrigendum to “Luteolin, a flavonoid, as an anticancer agent: A review” [Biomed. Pharmacother. 112 (2019) 108612]. Biomed. Pharmacother. 2019, 116, 109084. [Google Scholar] [CrossRef] [PubMed]
  39. Liu, F.; Guo, C.; Liu, X.; Gu, Z.; Zou, W.; Tang, X.; Tang, J. Luteolin in Inflammatory Bowel Disease and Colorectal Cancer: A Disease Continuum Perspective. Curr. Issues Mol. Biol. 2025, 47, 126. [Google Scholar] [CrossRef] [PubMed]
  40. Tang, L.; Gao, J.; Li, X.; Cao, X.; Zhou, B. Molecular Mechanisms of Luteolin Against Atopic Dermatitis Based on Network Pharmacology and in vivo Experimental Validation. Drug Des. Devel. Ther. 2022, 16, 4205–4221. [Google Scholar] [CrossRef]
  41. Li, Y.; Shen, L.; Luo, H. Luteolin ameliorates dextran sulfate sodium-induced colitis in mice possibly through activation of the Nrf2 signaling pathway. Int. Immunopharmacol. 2016, 40, 24–31. [Google Scholar] [CrossRef]
  42. He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol. Biochem. 2017, 44, 532–553. [Google Scholar] [CrossRef] [PubMed]
  43. Li, B.; Du, P.; Du, Y.; Zhao, D.; Cai, Y.; Yang, Q.; Guo, Z. Luteolin alleviates inflammation and modulates gut microbiota in ulcerative colitis rats. Life Sci. 2021, 269, 119008. [Google Scholar] [CrossRef]
  44. Neurath, M.F.; Vieth, M. Different levels of healing in inflammatory bowel diseases: Mucosal, histological, transmural, barrier and complete healing. Gut 2023, 72, 2164–2183. [Google Scholar] [CrossRef]
  45. Li, B.L.; Zhao, D.Y.; Du, P.L.; Wang, X.T.; Yang, Q.; Cai, Y.R. Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway. Inflamm. Res. 2021, 70, 705–717. [Google Scholar] [CrossRef]
  46. Singh, R.; Chandrashekharappa, S.; Bodduluri, S.R.; Baby, B.V.; Hegde, B.; Kotla, N.G.; Hiwale, A.A.; Saiyed, T.; Patel, P.; Vijay-Kumar, M.; et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat. Commun. 2019, 10, 89. [Google Scholar] [CrossRef]
  47. Luo, B.; An, Q.; Lei, J.; Tan, D.; Liu, X.; Li, H.; Zhao, Y.; Qin, J.; Zhang, C.; Zhang, Y.; et al. Resveratrol amplifies the anti-tumor effect of α-PD-1 by altering the intestinal microbiome and PGD2 content. Gut Microbes. 2025, 17, 2447821. [Google Scholar] [CrossRef]
  48. Zhou, H.; Zhuang, Y.; Liang, Y.; Chen, H.; Qiu, W.; Xu, H.; Zhou, H. Curcumin exerts anti-tumor activity in colorectal cancer via gut microbiota-mediated CD8(+) T Cell tumor infiltration and ferroptosis. Food Funct. 2025, 16, 3671–3693. [Google Scholar] [CrossRef]
  49. Shabbir, U.; Rubab, M.; Daliri, E.B.; Chelliah, R.; Javed, A.; Oh, D.H. Curcumin, Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota. Nutrients 2021, 13, 206. [Google Scholar] [CrossRef] [PubMed]
  50. McFadden, R.M.; Larmonier, C.B.; Shehab, K.W.; Midura-Kiela, M.; Ramalingam, R.; Harrison, C.A.; Besselsen, D.G.; Chase, J.H.; Caporaso, J.G.; Jobin, C.; et al. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention. Inflamm. Bowel Dis. 2015, 21, 2483–2494. [Google Scholar] [CrossRef] [PubMed]
  51. Qi, Y.; Gao, F.; Hou, L.; Wan, C. Anti-Inflammatory and Immunostimulatory Activities of Astragalosides. Am. J. Chin. Med. 2017, 45, 1157–1167. [Google Scholar] [CrossRef]
  52. Luo, H.; Vong, C.T.; Chen, H.; Gao, Y.; Lyu, P.; Qiu, L.; Zhao, M.; Liu, Q.; Cheng, Z.; Zou, J.; et al. Naturally occurring anti-cancer compounds: Shining from Chinese herbal medicine. Chin. Med. 2019, 14, 48. [Google Scholar] [CrossRef]
  53. Fan, W.; Huang, Y.; Zheng, H.; Li, S.; Li, Z.; Yuan, L.; Cheng, X.; He, C.; Sun, J. Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms. Biomed. Pharmacother. 2020, 132, 110915. [Google Scholar] [CrossRef]
  54. Zhou, Z.; Li, M.; Zhang, Z.; Song, Z.; Xu, J.; Zhang, M.; Gong, M. Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases. J. Ethnopharmacol. 2024, 334, 118506. [Google Scholar] [CrossRef]
  55. Zhou, N.; Tang, Y.; Keep, R.F.; Ma, X.; Xiang, J. Antioxidative effects of Panax notoginseng saponins in brain cells. Phytomedicine 2014, 21, 1189–1195. [Google Scholar] [CrossRef] [PubMed]
  56. Baik, I.H.; Kim, K.H.; Lee, K.A. Antioxidant, Anti-Inflammatory and Antithrombotic Effects of Ginsenoside Compound K Enriched Extract Derived from Ginseng Sprouts. Molecules 2021, 26, 4102. [Google Scholar] [CrossRef]
  57. Khan, M.I.; Karima, G.; Khan, M.Z.; Shin, J.H.; Kim, J.D. Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. Int. J. Mol. Sci. 2022, 23, 10665. [Google Scholar] [CrossRef] [PubMed]
  58. Zhou, R.; Guo, T.; Li, J. Research progress on the antitumor effects of astragaloside IV. Eur. J. Pharmacol. 2023, 938, 175449. [Google Scholar] [CrossRef]
  59. Choi, Y.H.; Yoo, D.S.; Cha, M.R.; Choi, C.W.; Kim, Y.S.; Choi, S.U.; Lee, K.R.; Ryu, S.Y. Antiproliferative effects of saponins from the roots of Platycodon grandiflorum on cultured human tumor cells. J. Nat. Prod. 2010, 73, 1863–1867. [Google Scholar] [CrossRef] [PubMed]
  60. Xia, T.; Zhang, B.; Li, Y.; Fang, B.; Zhu, X.; Xu, B.; Zhang, J.; Wang, M.; Fang, J. New insight into 20(S)-ginsenoside Rh2 against T-cell acute lymphoblastic leukemia associated with the gut microbiota and the immune system. Eur. J. Med. Chem. 2020, 203, 112582. [Google Scholar] [CrossRef]
  61. Yousuf, S.; Liu, H.; Yingshu, Z.; Zahid, D.; Ghayas, H.; Li, M.; Ding, Y.; Li, W. Ginsenoside Rg1 modulates intestinal microbiota and supports re-generation of immune cells in dexamethasone-treated mice. Acta Microbiol. Immunol. Hung. 2022, 69, 259–269. [Google Scholar] [CrossRef] [PubMed]
  62. Bai, X.; Fu, R.; Liu, Y.; Deng, J.; Fei, Q.; Duan, Z.; Zhu, C.; Fan, D. Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis. J. Pharm. Anal. 2024, 14, 259–275. [Google Scholar] [CrossRef]
  63. Ran, J.; Ai, Y.; Ni, J.; Zhang, Y.; Chen, J.; Wang, T.; Ma, J.; Zheng, J.; Li, R.; Ma, X.; et al. Astragaloside IV: A Promising Drug to Prevent the Transition from Colitis to Colorectal Cancer. Am. J. Chin. Med. 2025, 53, 1065–1091. [Google Scholar] [CrossRef] [PubMed]
  64. Hamid, O.; Robert, C.; Daud, A.; Hodi, F.S.; Hwu, W.J.; Kefford, R.; Wolchok, J.D.; Hersey, P.; Joseph, R.W.; Weber, J.S.; et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 2013, 369, 134–144. [Google Scholar] [CrossRef]
  65. Ma, S.; Li, X.; Wang, X.; Cheng, L.; Li, Z.; Zhang, C.; Ye, Z.; Qian, Q. Current Progress in CAR-T Cell Therapy for Solid Tumors. Int. J. Biol. Sci. 2019, 15, 2548–2560. [Google Scholar] [CrossRef]
  66. Chrysostomou, D.; Roberts, L.A.; Marchesi, J.R.; Kinross, J.M. Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy. Gastroenterology 2023, 164, 198–213. [Google Scholar] [CrossRef]
  67. Li, Z.; Xiong, W.; Liang, Z.; Wang, J.; Zeng, Z.; Kołat, D.; Li, X.; Zhou, D.; Xu, X.; Zhao, L. Critical role of the gut microbiota in immune responses and cancer immunotherapy. J. Hematol. Oncol. 2024, 17, 33. [Google Scholar] [CrossRef]
  68. Fernandes, M.R.; Aggarwal, P.; Costa, R.G.F.; Cole, A.M.; Trinchieri, G. Targeting the gut microbiota for cancer therapy. Nat. Rev. Cancer 2022, 22, 703–722. [Google Scholar] [CrossRef]
  69. Park, E.M.; Chelvanambi, M.; Bhutiani, N.; Kroemer, G.; Zitvogel, L.; Wargo, J.A. Targeting the gut and tumor microbiota in cancer. Nat. Med. 2022, 28, 690–703. [Google Scholar] [CrossRef]
  70. Sivan, A.; Corrales, L.; Hubert, N.; Williams, J.B.; Aquino-Michaels, K.; Earley, Z.M.; Benyamin, F.W.; Lei, Y.M.; Jabri, B.; Alegre, M.L.; et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015, 350, 1084–1089. [Google Scholar] [CrossRef] [PubMed]
  71. Marcos-Kovandzic, L.; Avagliano, M.; Ben Khelil, M.; Srikanthan, J.; Abdallah, R.; Petrocelli, V.; Rengassamy, J.; Alfaro, A.; Bied, M.; Fidelle, M.; et al. Gut microbiota modulation through Akkermansia spp. supplementation increases CAR-T cell potency. Cancer Discov. 2025, 15, 1905–1926. [Google Scholar] [CrossRef]
  72. Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef]
  73. Webb, E.S.; Liu, P.; Baleeiro, R.; Lemoine, N.R.; Yuan, M.; Wang, Y.H. Immune checkpoint inhibitors in cancer therapy. J. Biomed. Res. 2018, 32, 317–326. [Google Scholar] [CrossRef]
  74. Granier, C.; De Guillebon, E.; Blanc, C.; Roussel, H.; Badoual, C.; Colin, E.; Saldmann, A.; Gey, A.; Oudard, S.; Tartour, E. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open 2017, 2, e000213. [Google Scholar] [CrossRef]
  75. Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Rutkowski, P.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Wagstaff, J.; Schadendorf, D.; Ferrucci, P.F.; et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 2017, 377, 1345–1356. [Google Scholar] [CrossRef]
  76. Ahmadzadeh, M.; Johnson, L.A.; Heemskerk, B.; Wunderlich, J.R.; Dudley, M.E.; White, D.E.; Rosenberg, S.A. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009, 114, 1537–1544. [Google Scholar] [CrossRef] [PubMed]
  77. Zhang, X.; Yu, D.; Wu, D.; Gao, X.; Shao, F.; Zhao, M.; Wang, J.; Ma, J.; Wang, W.; Qin, X.; et al. Tissue-resident Lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance. Cell Host Microbe. 2023, 31, 418–432.e418. [Google Scholar] [CrossRef]
  78. Zong, G.; Deng, R.; Pan, Y.; Liu, M.; Zhu, H.; Tao, R.; Shan, Y.; Wei, Z.; Lu, Y. Ginseng polysaccharides ameliorate colorectal tumorigenesis through Lachnospiraceae-mediated immune modulation. Int. J. Biol. Macromol. 2025, 307, 142015. [Google Scholar] [CrossRef] [PubMed]
  79. Zhang, G.; Pan, J.; Xu, X.; Nie, S.; Lu, L.; Jing, Y.; Yang, F.; Ji, G.; Xu, H. Chinese yam polysaccharide enhances anti-PD-1 immunotherapy in colorectal cancer through alterations in the gut microbiota and metabolites. Int. J. Biol. Macromol. 2025, 310, 143323. [Google Scholar] [CrossRef] [PubMed]
  80. Wang, L.; Jiang, G.; Jing, N.; Liu, X.; Li, Q.; Liang, W.; Liu, Z. Bilberry anthocyanin extracts enhance anti-PD-L1 efficiency by modulating gut microbiota. Food Funct. 2020, 11, 3180–3190. [Google Scholar] [CrossRef]
  81. Rooks, M.G.; Garrett, W.S. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 2016, 16, 341–352. [Google Scholar] [CrossRef]
  82. Krautkramer, K.A.; Fan, J.; Bäckhed, F. Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Microbiol. 2021, 19, 77–94. [Google Scholar] [CrossRef]
  83. Davar, D.; Dzutsev, A.K.; McCulloch, J.A.; Rodrigues, R.R.; Chauvin, J.M.; Morrison, R.M.; Deblasio, R.N.; Menna, C.; Ding, Q.; Pagliano, O.; et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 2021, 371, 595–602. [Google Scholar] [CrossRef]
  84. Yang, Q.; Wang, B.; Zheng, Q.; Li, H.; Meng, X.; Zhou, F.; Zhang, L. A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy. Adv. Sci. 2023, 10, e2207366. [Google Scholar] [CrossRef] [PubMed]
  85. Zhang, X.; Jia, L.; Ma, Q.; Zhang, X.; Chen, M.; Liu, F.; Zhang, T.; Jia, W.; Zhu, L.; Qi, W.; et al. Astragalus Polysaccharide Modulates the Gut Microbiota and Metabolites of Patients with Type 2 Diabetes in an In Vitro Fermentation Model. Nutrients 2024, 16, 1698. [Google Scholar] [CrossRef]
  86. Tian, Y.; Wu, J.; Zheng, Y.; Li, M.; Xu, X.; Chen, H.; Rui, W. Structural changes of polysaccharides from Astragulus after honey processing and their bioactivities on human gut microbiota. J. Sci. Food Agric. 2023, 103, 7241–7250. [Google Scholar] [CrossRef] [PubMed]
  87. Yue, B.; Zong, G.; Tao, R.; Wei, Z.; Lu, Y. Crosstalk between traditional Chinese medicine-derived polysaccharides and the gut microbiota: A new perspective to understand traditional Chinese medicine. Phytother. Res. 2022, 36, 4125–4138. [Google Scholar] [CrossRef]
  88. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252. [Google Scholar] [CrossRef]
  89. Thangaraju, M.; Cresci, G.A.; Liu, K.; Ananth, S.; Gnanaprakasam, J.P.; Browning, D.D.; Mellinger, J.D.; Smith, S.B.; Digby, G.J.; Lambert, N.A.; et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009, 69, 2826–2832. [Google Scholar] [CrossRef] [PubMed]
  90. Singh, N.; Thangaraju, M.; Prasad, P.D.; Martin, P.M.; Lambert, N.A.; Boettger, T.; Offermanns, S.; Ganapathy, V. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem. 2010, 285, 27601–27608. [Google Scholar] [CrossRef]
  91. Sun, M.; Wu, W.; Chen, L.; Yang, W.; Huang, X.; Ma, C.; Chen, F.; Xiao, Y.; Zhao, Y.; Ma, C.; et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat. Commun. 2018, 9, 3555. [Google Scholar] [CrossRef]
  92. Wang, L.; Chen, J.; Chen, Q.; Song, H.; Wang, Z.; Xing, W.; Jin, S.; Song, X.; Yang, H.; Zhao, W. The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B. Oxid. Med. Cell. Longev. 2023, 2023, 6480848. [Google Scholar] [CrossRef]
  93. Tomás-Barberán, F.A.; González-Sarrías, A.; García-Villalba, R.; Núñez-Sánchez, M.A.; Selma, M.V.; García-Conesa, M.T.; Espín, J.C. Urolithins, the rescue of “old” metabolites to understand a “new” concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol. Nutr. Food Res. 2017, 61, 1500901. [Google Scholar] [CrossRef]
  94. Lo, B.C.; Kryczek, I.; Yu, J.; Vatan, L.; Caruso, R.; Matsumoto, M.; Sato, Y.; Shaw, M.H.; Inohara, N.; Xie, Y.; et al. Microbiota-dependent activation of CD4(+) T cells induces CTLA-4 blockade-associated colitis via Fcγ receptors. Science 2024, 383, 62–70. [Google Scholar] [CrossRef]
  95. Zhou, Y.; Medik, Y.B.; Patel, B.; Zamler, D.B.; Chen, S.; Chapman, T.; Schneider, S.; Park, E.M.; Babcock, R.L.; Chrisikos, T.T.; et al. Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration. J. Exp. Med. 2023, 220, e20221333. [Google Scholar] [CrossRef]
  96. Simpson, R.C.; Shanahan, E.R.; Batten, M.; Reijers, I.L.M.; Read, M.; Silva, I.P.; Versluis, J.M.; Ribeiro, R.; Angelatos, A.S.; Tan, J.; et al. Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome. Nat. Med. 2022, 28, 2344–2352. [Google Scholar] [CrossRef]
  97. Michot, J.M.; Bigenwald, C.; Champiat, S.; Collins, M.; Carbonnel, F.; Postel-Vinay, S.; Berdelou, A.; Varga, A.; Bahleda, R.; Hollebecque, A.; et al. Immune-related adverse events with immune checkpoint blockade: A comprehensive review. Eur. J. Cancer 2016, 54, 139–148. [Google Scholar] [CrossRef]
  98. Takiishi, T.; Fenero, C.I.M.; Câmara, N.O.S. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers 2017, 5, e1373208. [Google Scholar] [CrossRef] [PubMed]
  99. Honda, K.; Littman, D.R. The microbiota in adaptive immune homeostasis and disease. Nature 2016, 535, 75–84. [Google Scholar] [CrossRef] [PubMed]
  100. Qi, P.; Yin, L.; Wei, R.; Yang, S.; Liu, Z.; Huang, P.; Yu, Q.; Xiong, S.; Wang, M.; Deng, Y.; et al. Chronic stress synergizes with Listeria monocytogenes to promote intestinal adenomagenesis via myeloid-derived suppressor cells. Front. Immunol. 2025, 16, 1653548. [Google Scholar] [CrossRef] [PubMed]
  101. Pramanik, A.; Bhattacharyya, S. Myeloid derived suppressor cells and innate immune system interaction in tumor microenvironment. Life Sci. 2022, 305, 120755. [Google Scholar] [CrossRef]
  102. Gill, G.S.; Kharb, S.; Goyal, G.; Das, P.; Kurdia, K.C.; Dhar, R.; Karmakar, S. Immune checkpoint inhibitors and immunosuppressive tumor microenvironment: Current challenges and strategies to overcome resistance. Immunopharmacol. Immunotoxicol. 2025, 47, 485–507. [Google Scholar] [CrossRef]
  103. Turner, J.R. Intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 2009, 9, 799–809. [Google Scholar] [CrossRef]
  104. Duan, Y.; Huang, J.; Sun, M.; Jiang, Y.; Wang, S.; Wang, L.; Yu, N.; Peng, D.; Wang, Y.; Chen, W.; et al. Poria cocos polysaccharide improves intestinal barrier function and maintains intestinal homeostasis in mice. Int. J. Biol. Macromol. 2023, 249, 125953. [Google Scholar] [CrossRef]
  105. Huo, J.; Wu, Z.; Sun, W.; Wang, Z.; Wu, J.; Huang, M.; Wang, B.; Sun, B. Protective Effects of Natural Polysaccharides on Intestinal Barrier Injury: A Review. J. Agric. Food Chem. 2022, 70, 711–735. [Google Scholar] [CrossRef]
  106. Ghosh, S.S.; He, H.; Wang, J.; Gehr, T.W.; Ghosh, S. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects. Tissue Barriers 2018, 6, e1425085. [Google Scholar] [CrossRef]
  107. Li, F.; Du, P.; Yang, W.; Huang, D.; Nie, S.; Xie, M. Polysaccharide from the seeds of Plantago asiatica L. alleviates nonylphenol induced intestinal barrier injury by regulating tight junctions in human Caco-2 cell line. Int. J. Biol. Macromol. 2020, 164, 2134–2140. [Google Scholar] [CrossRef] [PubMed]
  108. Li, W.; Gao, M.; Han, T. Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells. Food Funct. 2020, 11, 3741–3748. [Google Scholar] [CrossRef]
  109. Wang, Q.; Liu, F.; Chen, X.; Yang, Z.; Cao, Y. Effects of the polysaccharide SPS-3-1 purified from Spirulina on barrier integrity and proliferation of Caco-2 cells. Int. J. Biol. Macromol. 2020, 163, 279–287. [Google Scholar] [CrossRef] [PubMed]
  110. Dougan, M.; Pietropaolo, M. Time to dissect the autoimmune etiology of cancer antibody immunotherapy. J. Clin. Investig. 2020, 130, 51–61. [Google Scholar] [CrossRef] [PubMed]
  111. Dougan, M. Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract. Front. Immunol. 2017, 8, 1547. [Google Scholar] [CrossRef] [PubMed]
  112. Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [PubMed]
  113. Postow, M.A.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.; McDermott, D.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 2015, 372, 2006–2017. [Google Scholar] [CrossRef]
  114. Postow, M.A.; Sidlow, R.; Hellmann, M.D. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N. Engl. J. Med. 2018, 378, 158–168. [Google Scholar] [CrossRef]
  115. Zhang, X.; Zhang, F.; Li, Y.; Fan, N.; Zhao, K.; Zhang, A.; Kang, J.; Lin, Y.; Xue, X.; Jiang, X. Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier. J. Transl. Med. 2024, 22, 406. [Google Scholar] [CrossRef]
  116. Peng, Y.; Ao, M.; Dong, B.; Jiang, Y.; Yu, L.; Chen, Z.; Hu, C.; Xu, R. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. Drug Des. Devel. Ther. 2021, 15, 4503–4525. [Google Scholar] [CrossRef]
  117. Zhao, J.; Jia, W.; Zhang, R.; Wang, X.; Zhang, L. Improving curcumin bioavailability: Targeted delivery of curcumin and loading systems in intestinal inflammation. Food Res. Int. 2024, 196, 115079. [Google Scholar] [CrossRef]
  118. Long, D.; Mao, C.; Zhang, W.; Zhu, Y.; Xu, Y. Natural products for the treatment of ulcerative colitis: Focus on the JAK/STAT pathway. Front. Immunol. 2025, 16, 1538302. [Google Scholar] [CrossRef]
  119. Jia, X.; Huang, Y.; Liu, G.; Li, Z.; Tan, Q.; Zhong, S. The Use of Polysaccharide AOP30 from the Rhizome of Alpinia officinarum Hance to Alleviate Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction and Inflammation via the TLR4/NfκB Signaling Pathway in Caco-2 Cell Monolayers. Nutrients 2024, 16, 2151. [Google Scholar] [CrossRef]
  120. Li, Z.; Chu, T.; Sun, X.; Zhuang, S.; Hou, D.; Zhang, Z.; Sun, J.; Liu, Y.; Li, J.; Bian, Y. Polyphenols-rich Portulaca oleracea L. (purslane) alleviates ulcerative colitis through restiring the intestinal barrier, gut microbiota and metabolites. Food Chem. 2025, 468, 142391. [Google Scholar] [CrossRef] [PubMed]
  121. Hanai, H.; Iida, T.; Takeuchi, K.; Watanabe, F.; Maruyama, Y.; Andoh, A.; Tsujikawa, T.; Fujiyama, Y.; Mitsuyama, K.; Sata, M.; et al. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 2006, 4, 1502–1506. [Google Scholar] [CrossRef] [PubMed]
  122. Shang, Q.; Liu, W.; Leslie, F.; Yang, J.; Guo, M.; Sun, M.; Zhang, G.; Zhang, Q.; Wang, F. Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy. Acta Pharm. Sin. B. 2024, 14, 1525–1541. [Google Scholar] [CrossRef] [PubMed]
  123. Sun, D.; Zou, Y.; Song, L.; Han, S.; Yang, H.; Chu, D.; Dai, Y.; Ma, J.; O’Driscoll, C.M.; Yu, Z.; et al. A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer. Acta Pharm. Sin. B 2022, 12, 378–393. [Google Scholar] [CrossRef]
  124. Man, S.; Liu, W.; Bi, J.; Bai, J.; Wu, Q.; Hu, B.; Hu, J.; Ma, L. Smart Mesoporous Silica Nanoparticles Loading Curcumin Inhibit Liver Cancer. J. Agric. Food Chem. 2024, 72, 25743–25754. [Google Scholar] [CrossRef]
  125. Peng, P.; Chen, Z.; Wang, M.; Wen, B.; Deng, X. Polysaccharide-modified liposomes and their application in cancer research. Chem. Biol. Drug Des. 2023, 101, 998–1011. [Google Scholar] [CrossRef]
  126. Wang, H.; Zheng, Y.; Sun, Q.; Zhang, Z.; Zhao, M.; Peng, C.; Shi, S. Ginsenosides emerging as both bifunctional drugs and nanocarriers for enhanced antitumor therapies. J. Nanobiotechnology 2021, 19, 322. [Google Scholar] [CrossRef]
  127. Dai, Q.; Wilhelm, S.; Ding, D.; Syed, A.M.; Sindhwani, S.; Zhang, Y.; Chen, Y.Y.; MacMillan, P.; Chan, W.C.W. Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors. ACS Nano 2018, 12, 8423–8435. [Google Scholar] [CrossRef]
  128. Liu, X.; Wu, Z.; Guo, C.; Guo, H.; Su, Y.; Chen, Q.; Sun, C.; Liu, Q.; Chen, D.; Mu, H. Hypoxia responsive nano-drug delivery system based on angelica polysaccharide for liver cancer therapy. Drug Deliv. 2022, 29, 138–148. [Google Scholar] [CrossRef] [PubMed]
  129. Lynam, S.; Lugade, A.A.; Odunsi, K. Immunotherapy for Gynecologic Cancer: Current Applications and Future Directions. Clin. Obstet. Gynecol. 2020, 63, 48–63. [Google Scholar] [CrossRef]
  130. Liu, M.; Zhang, Z.X.; Wang, J.H.; Guo, R.B.; Zhang, L.; Kong, L.; Yu, Y.; Zang, J.; Liu, Y.; Li, X.T. Immunomodulatory and anti-ovarian cancer effects of novel astragalus polysaccharide micelles loaded with podophyllotoxin. Int. J. Biol. Macromol. 2025, 290, 138960. [Google Scholar] [CrossRef]
  131. Nel, A.; Xia, T.; Mädler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622–627. [Google Scholar] [CrossRef]
  132. Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol. 2015, 6, 286. [Google Scholar] [CrossRef]
  133. Oude Blenke, E.; Mastrobattista, E.; Schiffelers, R.M. Strategies for triggered drug release from tumor targeted liposomes. Expert Opin. Drug Deliv. 2013, 10, 1399–1410. [Google Scholar] [CrossRef] [PubMed]
  134. Moein Moghimi, S.; Hamad, I.; Bünger, R.; Andresen, T.L.; Jørgensen, K.; Hunter, A.C.; Baranji, L.; Rosivall, L.; Szebeni, J. Activation of the human complement system by cholesterol-rich and PEGylated liposomes-modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels. J. Liposome Res. 2006, 16, 167–174. [Google Scholar] [CrossRef]
  135. Szebeni, J.; Baranyi, L.; Savay, S.; Bodo, M.; Morse, D.S.; Basta, M.; Stahl, G.L.; Bünger, R.; Alving, C.R. Liposome-induced pulmonary hypertension: Properties and mechanism of a complement-mediated pseudoallergic reaction. Am. J. Physiol. Heart Circ. Physiol. 2000, 279, H1319–H1328. [Google Scholar] [CrossRef]
  136. Su, Y.; Wang, L.; Liang, K.; Liu, M.; Liu, X.; Song, Y.; Deng, Y. The accelerated blood clearance phenomenon of PEGylated nanoemulsion upon cross administration with nanoemulsions modified with polyglycerin. Asian J. Pharm. Sci. 2018, 13, 44–53. [Google Scholar] [CrossRef]
  137. Verhoef, J.J.; Anchordoquy, T.J. Questioning the Use of PEGylation for Drug Delivery. Drug Deliv. Transl. Res. 2013, 3, 499–503. [Google Scholar] [CrossRef] [PubMed]
  138. Atanase, L.I. Micellar Drug Delivery Systems Based on Natural Biopolymers. Polymers 2021, 13, 477. [Google Scholar] [CrossRef] [PubMed]
  139. Vijayakumar, A.; Baskaran, R.; Maeng, H.J.; Yoo, B.K. Ginsenoside improves physicochemical properties and bioavailability of curcumin-loaded nanostructured lipid carrier. Arch. Pharm. Res. 2017, 40, 864–874. [Google Scholar] [CrossRef]
  140. Hong, C.; Liang, J.; Xia, J.; Zhu, Y.; Guo, Y.; Wang, A.; Lu, C.; Ren, H.; Chen, C.; Li, S.; et al. One Stone Four Birds: A Novel Liposomal Delivery System Multi-functionalized with Ginsenoside Rh2 for Tumor Targeting Therapy. Nano-Micro Lett. 2020, 12, 129. [Google Scholar] [CrossRef]
  141. Fox, C.B.; Kim, J.; Le, L.V.; Nemeth, C.L.; Chirra, H.D.; Desai, T.A. Micro/nanofabricated platforms for oral drug delivery. J. Control. Release 2015, 219, 431–444. [Google Scholar] [CrossRef]
  142. Laffleur, F.; Mayer, A.H. Oral nanoparticulate drug delivery systems for the treatment of intestinal bowel disease and colorectal cancer. Expert Opin. Drug Deliv. 2023, 20, 1595–1607. [Google Scholar] [CrossRef]
  143. Krishnaiah, Y.S.; Khan, M.A. Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer. Pharm. Dev. Technol. 2012, 17, 521–540. [Google Scholar] [CrossRef]
  144. Chourasia, M.K.; Jain, S.K. Polysaccharides for colon targeted drug delivery. Drug Deliv. 2004, 11, 129–148. [Google Scholar] [CrossRef]
  145. Gong, T.; Liu, X.; Wang, X.; Lu, Y.; Wang, X. Applications of polysaccharides in enzyme-triggered oral colon-specific drug delivery systems: A review. Int. J. Biol. Macromol. 2024, 275, 133623. [Google Scholar] [CrossRef]
  146. Meng, Y.; Qiu, C.; Li, X.; McClements, D.J.; Sang, S.; Jiao, A.; Jin, Z. Polysaccharide-based nano-delivery systems for encapsulation, delivery, and pH-responsive release of bioactive ingredients. Crit. Rev. Food Sci. Nutr. 2024, 64, 187–201. [Google Scholar] [CrossRef]
  147. Gao, Q.; Chen, N.; Li, B.; Zu, M.; Ma, Y.; Xu, H.; Zhu, Z.; Reis, R.L.; Kundu, S.C.; Xiao, B. Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route. J. Nanobiotechnology 2024, 22, 4. [Google Scholar] [CrossRef]
  148. Jin, C.; Lagoudas, G.K.; Zhao, C.; Bullman, S.; Bhutkar, A.; Hu, B.; Ameh, S.; Sandel, D.; Liang, X.S.; Mazzilli, S.; et al. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell 2019, 176, 998–1013.e1016. [Google Scholar] [CrossRef]
Nutrients 17 03591 g001
Figure 1. The Interaction between bioactive compounds from edible and medicinal plants and gut microbiota in cancer immunomodulation. Created with biorender.com.
Figure 1. The Interaction between bioactive compounds from edible and medicinal plants and gut microbiota in cancer immunomodulation. Created with biorender.com.
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Figure 2. The interaction bioactive compounds from edible and medicinal plants and gut microbiota in cancer immune response. Created with biorender.com.
Figure 2. The interaction bioactive compounds from edible and medicinal plants and gut microbiota in cancer immune response. Created with biorender.com.
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Figure 3. Natural bioactive compounds from edible and medicinal plants improve intestinal barrier dysfunction and alleviate intestinal inflammation in cancer immunotherapy. Created with biorender.com.
Figure 3. Natural bioactive compounds from edible and medicinal plants improve intestinal barrier dysfunction and alleviate intestinal inflammation in cancer immunotherapy. Created with biorender.com.
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Figure 4. Drug delivery systems constructed from bioactive components of medicinal-edible plants enable precise drug release at specific sites and modulate immune responses against cancer. Created with biorender.com.
Figure 4. Drug delivery systems constructed from bioactive components of medicinal-edible plants enable precise drug release at specific sites and modulate immune responses against cancer. Created with biorender.com.
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MDPI and ACS Style

Peng, L.; Wang, L.; Zhao, Y.; Yu, P.; Yang, H. Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy. Nutrients 2025, 17, 3591. https://doi.org/10.3390/nu17223591

AMA Style

Peng L, Wang L, Zhao Y, Yu P, Yang H. Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy. Nutrients. 2025; 17(22):3591. https://doi.org/10.3390/nu17223591

Chicago/Turabian Style

Peng, Lu, Long Wang, Yingtong Zhao, Peng Yu, and Hongmei Yang. 2025. "Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy" Nutrients 17, no. 22: 3591. https://doi.org/10.3390/nu17223591

APA Style

Peng, L., Wang, L., Zhao, Y., Yu, P., & Yang, H. (2025). Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy. Nutrients, 17(22), 3591. https://doi.org/10.3390/nu17223591

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