Precision nutrition based on food-derived delivery systems for intestinal health: A review of natural carriers, construction strategies and advantages

Abstract

Bioactive substances face challenges in delivery to the intestine owing to low oral bioavailability. Constructing steady delivery systems based on food-derived natural carriers can overcome gastrointestinal barriers. Therefore, gaining insights into the multiple roles of natural delivery carriers will facilitate precision nutrition in intestinal health. This review highlighted the potential benefits of food-derived natural carriers for intestinal disease intervention by systematically summarizing the current progress on their sources and properties. The construction strategies, including freeze-drying rehydration technology, ionic crosslinking, electroporation, ultracentrifugation, and metal-phenolic networks, were applied to food-derived natural carriers by considering their targeting capability and stimulus responsiveness. Moreover, special attention should be given to applications, advantages, challenges, and future prospects of natural delivery carriers in precision intestinal nutrition. Overall, developing natural active carriers to deliver bioactive compounds to the intestine is a promising alternative for the treatment of intestinal disorders, which provide the theoretical basis for its industrialized application.

Highlights

• •Food-derived delivery systems for precision intestinal nutrition are reviewed.
• •Natural carriers increase the bioavailability and stability of active substances.
• •Delivery systems strengthen the targeting capability and stimuli responsiveness.
• •Natural carriers offer better functionality and biocompatibility of nutraceuticals.
• •Engineering preparation and clinical use of natural carriers should be studied.

1. Introduction

Intestinal disorders represent a prevalent category of ailments that impact global health, and they can be classified into two main types: functional and structural gastrointestinal disorders (Huang et al., 2023). Functional intestinal disorders encompass various conditions, such as functional dyspepsia, irritable bowel syndrome (IBS), and functional constipation, collectively affecting approximately one-third of the global population. Although the precise etiology of these conditions remains elusive, they are generally associated with disorders in gastrointestinal motility, visceral hypersensitivity, alterations in mucosal and immune functions, dysbiosis of the intestinal microbiota, and psychological influences (Gong et al., 2024). On the other hand, structural intestinal disorders primarily include conditions, such as inflammatory bowel disease (IBD) and colorectal cancer. IBD is a chronic condition characterized by complex pathogenesis that involves interactions among genetic predispositions, environmental factors, gut microbiota, and immune system. Intestinal disease not only markedly diminishes the quality of life for affected individuals but also imposes substantial economic burdens on healthcare systems (Alatab et al., 2020).

Due to the complex etiology and variable patient responses to intestinal diseases, the focus of the field has, accordingly, shifted towards pursuing precision nutrition as a promising therapeutic strategy. Central to precision nutrition is developing advanced delivery systems designed to improve bioavailability and maximise intestinal absorption rates of nutraceuticals or drugs. Currently, the predominant methods for delivering bioactive components for intestinal disorders include intravenous injection, topical administration, and oral administration. Intravenous administration frequently results in systemic side effects due to its limited targeting affinity. Topical administration often fails to reach deeper tissues effectively, thus limiting its practical applications. By contrast, oral administration is increasingly becoming the focus of research owing to its convenience, non-invasiveness, and high patient acceptance (Huang et al., 2023). However, traditional oral delivery systems often suffer from low bioavailability due to the complex nature of the gastrointestinal environment, which includes degradation by gastric acid and enzymes. Additionally, various physiological and pathological states of the gastrointestinal tract, such as inflammation and impaired intestinal barrier function, can further compromise drug effectiveness. Consequently, there is a burgeoning interest in developing more efficient drug delivery methods, particularly those involving delivery carriers capable of carrying bioactive components to overcome these barriers and to ensure stable drug release within the intestinal environment.

Conventional delivery carriers of bioactive substances, such as liposomes, micelles, emulsion gels, microcapsules and nano/micro-particles, have limited drug loading capacity, which is usually loaded by passive embedding or physical adsorption. In particular, some polymers, metals, or inorganic carriers are not easily removed by metabolism or degradation, leading to accumulation in the human body, which may trigger inflammatory or immune responses. In addition, traditional carriers may rely mainly on the enhanced osmotic retention effect (EPR), but the tumour heterogeneity and the complexity of the microenvironment may reduce the targeting efficiency. The carrier material usually lacks pharmacological activity and, only as a tool for drug delivery, fails to form a synergistic therapeutic effect with drugs (Etter et al., 2021). Conversely, food-derived natural carriers, which are considered safe, efficient and promising delivery platforms, have emerged as a significant area of interest in recent drug delivery research. Derived from food ingredients like plant polysaccharides, fungal spores, and microalgae, these carriers offer advantages such as excellent biocompatibility, low toxicity and biodegradability, making them highly promising for drug delivery applications (Frosi et al., 2024).

With the rising prevalence of intestinal disorders, traditional oral drug delivery systems are encountering difficulty in crossing the intestinal mucosal barrier of the gastrointestinal tract, highlighting the critical need for innovative and effective oral drug delivery systems. The unique features and functions of natural carriers make them emerging candidates as therapeutic agents and drug delivery platforms. In this review, the natural carriers based on food ingredients for nutritional intervention in intestinal diseases were summarized, with an emphasis on the biocompatible and biodegradable performance of those carriers. Firstly, the origins and properties of natural carriers as colon-targeted delivery carriers were introduced. Subsequently, their fabrication strategies and advantages, including stimuli responsiveness, mucoadhesive and mucus-penetrating properties, the abilities to target inflammation and co-delivery bioactive compounds, were reviewed. Finally, the challenges in nutritional field and future research directions were discuss (Fig. 1). This work contributes novel insights and methodologies for the management of intestinal disorders and serves as a foundation for further research and application of food-derived carriers in biological and pharmaceutical fields (Table 1 and Table 2).

Fig. 1.

Schematic diagram of necessity, mechanism, preparation, advantage, application and challenge of food-derived delivery systems.

Table 1.

Sources, main constituents and properties of natural carriers in food-derived delivery systems.

Classification	Carriers	Main constituents	Particle size	Properties	References
Microalgae source	Spirulina	Polysaccharides, phycocyanin and chlorophyll	3–5 μm	•Biodegradability that allows for renal clearance; •Negative surface charge that allows electrostatic adsorption of positively charged drugs; •Fluorescence imaging capability that enables non-invasive in vivo imaging. •Biodegradability: Clearance through the kidneys; •Negative surface charge: Electrostatic adsorption with positively charged drugs; •Fluorescence imaging capability: Non-invasive in vivo imaging.	(Xu, Luo, et al., 2024)
	Chlorella	Protein, polysaccharides, and chlorella growth factor	2–10 μm	•Particles that deliver drugs by physical adsorption or encapsulation; •Negatively charged cellulose cell walls that adsorb positively charged drugs by electrostatic adsorption; •Surface pores that allow small molecule drug penetration. •Spherical or ellipsoidal morphology: Drug loading by physical adsorption or encapsulation; •Negatively charged cellulose cell wall: Electrostatic adsorption of positively charged drug molecules; •Surface pores: Penetration of small molecule drugs.	(Liu, Dong, et al., 2024; Lorenzo et al., 2023)
	Diatom	Biosilicon, polysaccharides and proteins	10–150 μm	•Self-assembled three-dimensional complex porous structure that is suitable for drug loading and release; •Biocompatibility of biosilicon that combines well with cells and tissues to reduce toxic reactions; •Biodegradability of biosilicon that can be safely removed in vivo after drug delivery to reduce the burden on the body; •Light-responsive properties of flagella that are used to design light-controlled drug delivery systems. •Self-assembled three-dimensional complex porous structure: Suitable for drug loading and release; •Biocompatibility of biosilicon: Good integration with cells and tissues and reduced toxicity; •Biodegradability of biosilicon: Complete removal in the body after drug delivery; •Photosensitivity: Design of light-controlled drug delivery system	(Phogat et al., 2021)
Cell source	Exosome	Lipids, proteins, nucleic acids and metabolites	40–160 nm	•Biocompatibility: Toxicity and immunogenicity of drug delivery in vivo; •Targeting: Binding to specific surface receptors to achieve targeted drug delivery, improvement of drug efficacy and reduction of normal tissue damage; •Stability: Protective effect of drugs and biomolecules inside the double-layer structure and extension of drug half-life to improve drug delivery efficiency.	(Kalluri & LeBleu, 2020)
	Microvesicles	Lipids, proteins, nucleic acids and metabolites	50–1000 nm	•Biocompatibility: Low toxicity of cell membranes; •Multifunctionality: Carrying capacity of multiple drugs and biomolecules and multi-target therapeutic effects; •Permeability: Permeability of biological barriers.	(Abbas et al., 2024)
Plant source	Sunflower pollen	Polysaccharides, proteins, phenolic compounds and carotenoids	20–35 μm	•Surfaces with spikes and nanopores: Ability to adsorb multiple drugs and rich sites for drug loading; •Ultrasound responsiveness: Drug release in response to ultrasound stimulation.	(Wen et al., 2023)
	Pine pollen	Polysaccharides, protein and vitamins	20–50 μm	•Biocompatibility: Reduced risk of immunogenicity and metabolic toxicity of synthetic carriers; •Nutritional richness: Rich in protein, vitamins, carbohydrates, etc.; •Protective effect: Antioxidant protection of drugs; •Synergistic effect: Synergistic effect with loaded drugs to exert anti-inflammatory, immunomodulatory and anti-tumour activities.	(Tao et al., 2024)
	Inulin	2,1-β-D-fructan	1–1000 nm or 1–1000 μm	•Biodegradability: Production of short-chain fatty acids after fermentation and decomposition by intestinal microbes; •Targetedness: Targeted drug delivery in the intestine; •Controlled release: Sustained and controlled release of drugs	(Akram et al., 2024)
	Chitosan	Amino-deoxy-D-glucan	150–200 nm	•Biodegradability: Production of glucosamine and sugar units after enzymatic digestion and their metabolic absorption; •Targeting: Targeted drug delivery in the intestine and prolonged intestinal retention time; •Drug permeability: Enhanced cross-cellular and paracellular transport of drugs and improved drug bioavailability	(Liu, Fu, et al., 2024)
	Pectin	Homogalacturonan (HG), rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II)	100–500 nm or 1–50 μm	•Biocompatibility: Biocompatibility with cells and tissues and reduction of immune response; •Three-dimensional hydrogel network: Control of drug release rate; •Environmental responsiveness: pH and temperature responsive release.	(Kapoor et al., 2024)
Microbial sources	Ganoderma lucidum spore	Cellulose, lignin, chitin and protein	7–9 μm	•Egg-shaped spindle shaps: Double-walled, large inner cavity and surface structure with uniform and abundant natural holes; •Functional surface: Multiple functional groups for further chemical modification; •Biocompatibility: No obvious tissue damage or toxic reaction and enhanced intestinal mucosal protective function.	(Liao et al., 2023)
	Yeast spores	β-1,3-glucan, mannan, chitin and protein	2–4 μm	•Immune stimulation: Induction of secretion of pro-inflammatory cytokines (such as IL-1β, IL-6, TNF-α, etc.) and enhancement of immune response; •Targeting: Specific phagocytosis of macrophages and dendritic cells; •Stability: Stability in gastric acid environment.	(Tan et al., 2022)

Table 2.

Fabrication strategies of food-derived delivery systems and their application in gastrointestinal disorders intervention.

Food-derived delivery systems	Natural carriers	Cargo delivery	Gastrointestinal disorders intervention	Mechanism of action	References
SP@Curcumin	Spirulina	Curcumin	Treatment of intestinal diseases such as colon cancer and colitis	• Targeting of drug delivery: Prolonging the residence time of the drug in the intestine, increasing the local concentration of the drug and enhancing the anti-inflammatory effect. • Radiotherapy protection: Removing ROS generated during radiotherapy, reducing DNA damage to normal tissues; protecting normal intestinal tissues from the side effects of radiotherapy. • Anti-inflammatory effect: Reducing the expression of inflammatory factors (such as TNF-α and IL-6) and inhibiting inflammatory response.	(Zhong et al., 2021)
CV@INS@ALG	Chlorella	Insulin	Regulation of intestinal microbiota to treat diabetes	• Drug release: Protecting insulin from degradation in gastric acid and releasing insulin in response to pH changes in the intestine. • Regulation of intestinal flora: Regulating intestinal flora, increasing the abundance of beneficial bacteria (such as Akkermansia) and improving insulin sensitivity.	(Ren et al., 2023)
“SMART” drug delivery system	Diatom	Curcumin	Treatment of chronic inflammatory diseases	• Anti-inflammatory effect: Inhibiting the production of inflammatory mediators and the activation of inflammatory cells, prolonging the drug's action time, reducing the distribution of drugs in non-inflammatory sites and increasing the concentration of drugs in inflammatory sites.	(Saxena et al., 2022)
Curcumin-loaded ginger-derived ganovesicles	Ginger source nanovesicles	Curcumin	Treatment of UC	• Targeting the colon: Delivering curcumin to the colon site, increasing the concentration of the drug in the lesion site and enhancing the therapeutic effect. • Modulation of inflammatory response: Inhibiting myeloperoxidase (MPO) activity in colon tissue, reducing the level of pro-inflammatory cytokines and increasing the level of anti-inflammatory cytokines. • Regulation of intestinal flora: Improving the composition and diversity of intestinal flora, increasing the relative abundance of beneficial bacteria (such as Lachnospiraceae, Ruminococcaceae, etc.) and reducing the relative abundance of harmful bacteria (such as Proteobacteria).	(Huang, Zhang, et al., 2024)
FX-MVs	Probiotic membrane vesicles	Fucoxanthin	Treatment of IBD	• Antioxidant effect: Enhancing the stability in the gastrointestinal tract by encapsulating and exerting antioxidant effects. • Anti-inflammatory effect: Promoting the transformation of M1 macrophages to M2 macrophages, reducing inflammation by secreting anti-inflammatory cytokines and inhibiting the production of pro-inflammatory cytokines. • Regulation of the intestinal flora: Reshaping the intestinal microbial community, increasing the abundance of beneficial bacteria and inhibiting the growth of harmful bacteria.	(Liang et al., 2023)
EL/AP@PS (t + Dex)	Sunflower pollen	Thrombin, dexamethasone	Treatment of IBD	• Dual-responsive drug release: pH responsiveness: Remaining stable in the gastric acid environment and releasing drug in the high pH of the intestinal environment. Enzyme responsiveness: Further releasing PS (t + Dex) due to the high activity of enzymes. • Inflammatory targeting: Binding to positively charged proteins at the site of inflammation and achieving inflammation targeting. • Mucosal adhesion: Adhering to the intestinal mucosa, increasing the local concentration of the drug at the site of inflammation and reducing systemic exposure. • Promotion of hemostasis: Promoting blood clotting. • Tissue repair: Promoting the repair of damaged intestinal mucosa, restoring intestinal barrier function by regulating macrophage polarization and inhibiting inflammatory cell infiltration. • Regulation of intestinal flora: Optimizing the composition of intestinal flora, increasing the relative abundance of beneficial bacteria and reducing the relative abundance of harmful bacteria.	(Wang et al., 2024)
Chinese herb pollen-derived micromotors	Sunflower pollen	Berberine	Treatment of stomach ulcers	• Comparison with free drugs: Prolonging the drug's residence time in the stomach, promoting the repair of gastric mucosa, reducing inflammatory cell infiltration and the expression of pro-inflammatory factors and increasing the expression of anti-inflammatory factors.	(Cai et al., 2024)
Honey stabilized inulin nanoparticles (INU NPs)	Inulin	Irinotecan hydrochloride trihydrate	Anti-colon cancer	• Highly efficient loading of hydrophilic drugs. • Significant anticancer activity.	(Joseph et al., 2024)
Inulin-based glycovesicle	Inulin	Levofloxacin	Treatment of salmonella infections	• Responsive release: Rapid release of disulfide bonds under the action of H2S. • Targeted delivery: Precisely targeting the site of inflammation and reducing the impact on healthy tissue. • Biocompatibility and stability: Remaining intact in the gastrointestinal tract to avoid early release of drugs at non-targeted sites.	(Xu, Niu, et al., 2024)
CS-PIP@PLGA NPs	Chitosan	Sanghuang polysaccharides	Treatment of IBD	• Regulation of macrophage polarization: Inhibiting macrophage polarization to M1 polarization. • Anti-inflammatory effect: Reducing the secretion of pro-inflammatory cytokines and increasing the level of anti-inflammatory cytokine. • Regulation of intestinal flora: Significantly improving the dysbiosis of intestinal flora induced by DSS, increasing the content of SCFA, and maintaining the integrity of the intestinal barrier.	(Bai et al., 2022)
FA/CUR-PEG-LPs@PC	pectin	Curcumin	Treatment of UC	• Targeted delivery: Highly expressing folate receptors at the site of inflammation due to the modification of folic acid on the surface of the liposome. • Control of drug release: Degrading in the colon due to the action of enzymes. • Anti-inflammatory effect: Exerting anti-inflammatory effects by inhibiting the activity of nuclear factor-κB (NF-κB) and reducing the production of inflammatory factors.	(Wu et al., 2023)
OMT/SA-NPs	pectin	Oxymatrine	Treatment of UC	• Targeting colon lesion sites: Using the specific binding of SA to the Siglec-9 receptor overexpressed on the surface of macrophages at colon lesion sites. • Control of drug release: Remaining stable in the gastrointestinal tract, gradually releasing the drug in the colon, prolonging the residence time of the drug in the colon site and improving the bioavailability of the drug. • Anti-inflammatory effect: Inhibiting inflammatory response by up-regulating the expression of anti-inflammatory and down-regulating the level of pro-inflammatory cytokines. • Protection of Intestinal barrier: Upregulating the expression of tight junction proteins, repairing intestinal barrier function, reducing the infiltration of inflammatory cells and reducing colon inflammation.	(Zhao, Jia, et al., 2024)
5-FU@mGLS	Ganoderma lucidum spores	5-Fluorouracil	Treatment of stomach cancer	• Targeted drug delivery via external magnetic field. • Reduction of rapid drug metabolism and excretion.	(Han et al., 2021)
CM@YM	Yeast microcapsules	Curcumin	Treatment of UC	• Drug protection and controlled release: Protecting Cur-MPN from the degradation, enhancing targeting and retention ability in the intestine. • Antioxidant effect: Efficiently scavenging superoxide anion and hydroxyl radical. • Regulation of intestinal flora: Increasing the abundance of beneficial bacteria, reducing the abundance of harmful bacteria and promoting gut health by. • Anti-inflammatory and immunomodulation: Inhibiting the M1-type polarization of macrophages, reducing the expression of pro-inflammatory cytokines and restoring intestinal immune homeostasis.	(Li, Sun, et al., 2024)

2. Sources and properties of natural carriers based food ingredients

2.1. Source of microalgae

Microalgae constitute a renewable resource abundant in bioactive compounds, including proteins, vitamins, and fatty acids. These constituents confer distinct advantages upon microalgae, making them unprecedented natural carriers for pharmaceutical delivery applications. Additionally, microalgae possess active surface areas, photosynthetic capabilities, and outstanding biocompatibility, which render them ideal for targeted drug delivery. It should be noted that the locomotion abilities of microalgae, driven by processes like phototaxis, magnetotaxis, and chemotaxis, further facilitate precise drug delivery via external stimuli, thereby enhancing therapeutic outcomes of intestinal diseases (Huang, Lang, et al., 2024).

2.1.1. Spirulina

Spirulina platensis (SP), a biodegradable microalgae, has a surface with pores of 14–16 nm, and a spiral diameter of 3–5 μm. These pores allow the entry of small-molecule drugs, thereby enhancing the loading capacity. Its spiral shape is easily mechanically retained, achieving passive targeting (Xu, Luo, et al., 2024). Moreover, SP is naturally rich in chlorophyll and possesses inherent fluorescent properties, which enable non-invasive imaging and real-time in vivo monitoring without the need for additional fluorescent markers. Importantly, SP can be biodegraded into natural products such as chlorophyll within the body, and the carrier residues without drugs are metabolized and excreted through the kidneys, with no significant toxicity (Zhong et al., 2020).

Recent studies have demonstrated that SP showed a huge potential in colon disease treatment as a delivery system for probiotics. Oral probiotic therapy for colitis faces two major technical bottlenecks: low survival rates of active strains in the digestive tract and difficulties in effective colonisation at inflamed intestinal sites, significantly limiting its clinical efficacy. Han, Zhang, et al. (2024) developed a composite delivery system by directionally loading chitosan-coated probiotics (BCCS) onto the surface of SP as a biocarrier based on electrostatic self-assembly. SP's unique helical structure actively embedded into intestinal villi, significantly prolonging local retention time and promoting sustained therapeutic effects. Meanwhile, endogenous superoxide dismutase (SOD) in SP effectively neutralises excess superoxide anions in the gut, protecting probiotic functions while reducing oxidative damage to intestinal epithelium and improving the inflammatory microenvironment. In addition, an oral delivery system (SP@AMF) was developed by encapsulating amifostine within SP, which not only achieved extensive distribution of the drug throughout the small intestine, but also markedly enhanced protection against radiation damage (Zhang et al., 2022). Notably, SP has the capability to modulate the balance of the intestinal microbiome, thereby contributing to intestinal health. This innovative approach offers a novel strategy for intestinal protection during cancer radiotherapy. Collectively, these drug delivery systems leverage the unique properties of SP and combine various drugs and therapeutic mechanisms to demonstrate substantial therapeutic efficacy and benefits across different clinical contexts.

2.1.2. Chlorella

Chlorella, a spherical, unicellular green alga with a diameter ranging from 2 to 10 μm, exhibits rapid growth and robust adaptability to diverse environmental conditions. It represents one of the most extensively researched and largest genera of microalgae, comprising approximately ten species. Chlorella is prevalently utilised as a health food supplement and in animal feed across various countries. This alga is enriched with antioxidants and offers multiple health benefits, including immune enhancement, blood sugar reduction, lipid-lowering, and anti-tumoral properties, thereby presenting vast potential applications in the fields of food and delivery carriers (Zheng et al., 2024). Ren et al. (2023) also described a chlorella-based oral insulin delivery system (CV@INS@ALG) that shielded insulin from rapid degradation in the acidic gastric environment. In the alkaline intestinal environment, the hydrogel swiftly degraded to release insulin, significantly enhancing its oral bioavailability. Furthermore, chlorella carriers facilitated targeted insulin delivery by being recognized and internalized by M cells and macrophages in the intestine, thereafter entering the bloodstream via the lymphatic system. In addition to direct insulin release, these carriers improved insulin absorption efficiency through cellular phagocytosis and subsequent entry into the bloodstream.

The intestine is a primary pathway for lead (Pb) exposure. Pb damages the gut barrier and disrupts the balance of the gut microbiota, forming a vicious cycle of “Pb absorption-inflammation-microbial dysbiosis”. Liu et al. (2023) utilised Chlorella vulgaris (CV), the anti-inflammatory drug molecule Berberine (BBR), and a carboxymethyl chitosan/sodium alginate composite (ALG) to construct a BBR-CV@ALG hydrogel system. This system effectively adsorbed and eliminated Pb from the body. The controlled release of BBR further mitigated tissue damage caused by lead exposure. Simultaneously, BBR-CV@ALG repaired the gut barrier and significantly increased the abundance of beneficial bacteria such as Akkermansia muciniphila and Lactobacillus taiwanensis, thereby maintaining intestinal homeostasis.

2.1.3. Diatom

Diatoms, as unicellular algae, exhibit a high degree of biocompatibility, tunable pore sizes, a vast specific surface area, low density, robust mechanical strength, and exceptional chemical inertness. The biodegradability of diatoms also mitigates potential toxicity concerns associated with their long-term accumulation in the body, making them exemplary candidates for intelligent drug delivery systems (Phogat et al., 2021). The innovative drug delivery system based on marine diatoms utilizes the unique three-dimensional nanoporous structure of the biogenic silicon shell to enhance drug adsorption and loading capacities markedly. The high specific surface area and uniform pore size distribution of the diatom shell ensure stable drug loading and sustained release. Additionally, diatoms with excellent biocompatibility and low toxicity maintain negligible cytotoxicity even at elevated concentrations (1000 μg/mL). It facilitates rapid drug release under physiological conditions, while the release rate moderates in acidic environments, better mimicking the human physiological environment and improving drug targeting and bioavailability (Saxena et al., 2022). These attributes confer significant advantages of diatoms in the realm of oral drug delivery.

However, the use of diatoms as a drug delivery system still has a low drug loading. Wang et al. (2025) developed an efficient carrier system for indomethacin delivery using the diatom shell of Thalassiosira weissflogii. Through the three-level strategy of “aminoisation-evaporation drug carrier-chitosan coating”, the system achieved a drug carrier rate of up to 58.78 %, and the drug release was extremely small in an acidic environment, which could avoid the degradation of gastric acid and ensured the complete arrival of indomethacin to the colon. In addition, chitosan coating could not only continuously release drugs, but also enhanced the biocompatibility of natural carriers, providing a new, efficient and safe delivery platform for the local treatment of IBD and colon cancer.

2.2. Source of cells

2.2.1. Exosomes

Extracellular vesicles (EVs) are membrane-bound structures secreted by cells. They play a crucial role in mediating intercellular communication (Njoku et al., 2025). These vesicles can be classified into four principal categories based on their origin, size, and biosynthetic pathways, including endoplasmic reticulum-derived small exosomes (50–150 nm), plasma membrane-derived medium-sized microvesicles (100–1000 nm), and apoptotic bodies, which range from 500 to 4000 nm in diameter. Exosomes represent a subtype of EVs, typically averaging about 100 nm in diameter (Menck et al., 2020). They are capable of efficiently transferring nucleic acids, proteins, and other cellular components, thus holding significant potential for diagnostic and therapeutic applications. Owing to their inherent targeting capabilities and biocompatibility, exosomes are particularly promising for treating a variety of diseases. They can evade immune detection, protect therapeutic agents from degradation, and facilitate targeted delivery via surface modifications (Kalluri & LeBleu, 2020).

Derived naturally from milk, milk exosomes exhibit remarkable stability attributed to their lipid bilayer structure and surface proteins, such as CD9 and CD63. These characteristics enable them to withstand harsh conditions encountered during oral administration, such as exposure to gastric acid and enzymatic degradation in the intestines. Their small size and negative charge allow them to efficiently penetrate the mucosal layer, facilitating targeted drug delivery. Research has demonstrated that milk exosomes could specifically transport anthocyanins to hepatocellular carcinomas via endocytosis. They leveraged their antioxidant properties to provoke a burst in reactive oxygen species (ROS) within tumour cells, disrupt mitochondrial function, impede cell cycle progression, and ultimately activate apoptotic pathways (Jiang, Sun, et al., 2024).

In addition to serving as delivery carriers, exosomes inherently play a vital role in the pharmacological mechanisms of drugs, transporting proteins, lipids, and RNA. For instance, exosomes derived from goat's milk have shown considerable promise in orally treating ulcerative colitis (UC) (Gao et al., 2024). They could cross the intestinal barrier, restore damaged epithelial cell microvilli and tight junctions, further reduce levels of pro-inflammatory cytokines (TNF-α and IL-6), and mitigate oxidative stress. Concurrently, they remodelled the intestinal flora and influenced bile acid and purine metabolism pathways. In addition, Kim et al. (2023) found that the lipid bilayer and negative charge characteristics of ginseng exosome-like nanoparticles (GENs) conferred excellent stability, enabling them to resist gastric and pancreatic enzymes and harsh intestinal conditions. Their small size and charge properties facilitated penetration through the mucosal layer, allowing for targeted oral delivery. Studies have indicated that GENs significantly diminished the expression of pro-inflammatory cytokines (TNF-α and IL-6) by inhibiting the NF-κB pathway, enhanced M2 macrophage polarization, up-regulated the anti-inflammatory cytokine IL-10, and modulated the balance of intestinal microbiota.

2.2.2. Microvesicles

Microvesicles (MVs) represent a distinct class of extracellular vesicles, with diameters ranging from 50 nm to 1000 nm. These carriers are pivotal in the regulation of critical biological processes, including inflammation, oxidative stress, immune responses, and tissue remodelling. Therefore, MVs hold promise as biomarkers and therapeutic agents, particularly in the realm of drug delivery (Abbas et al., 2024).

Engineered probiotic membrane vesicles efficiently encapsulated fucoxanthin (FX) and delivered FX directly to sites of colonic inflammation via oral administration. These delivery systems, named as FX-MVs, exhibited excellent biocompatibility and immune tolerance, and notably enhanced the gastrointestinal stability of encapsulated FX, thereby shielding them from digestive degradation. In vivo studies have demonstrated that FX-MVs significantly mitigate the symptoms and pathological manifestations of colitis. This was achieved through the modulation of macrophage polarization, suppression of pro-inflammatory cytokine secretion, augmentation of antioxidant capabilities, and restoration of intestinal microbiota balance (Liang et al., 2023). In another research, ginger-derived nanovesicles (GDNVs) were designed to target the colon specifically, which significantly increased drug concentration at the site of lesions and thus, amplified therapeutic efficacy. Consequently, GDNVs could be utilised to develop curcumin-loaded ginger-derived nanovesicles, which demonstrated a drug-loading capacity of up to 94.027 % and an encapsulation efficiency of 89.300 %. GDNVs were also rich in bioactive compounds such as gingerol and phosphatidic acid, which possessed anti-inflammatory and antioxidant properties among other pharmacological effects. These components not only regulated the intestinal flora but also reshaped the intestinal microbiota, thereby providing adjunctive therapeutic benefits. These studies emphasise the potential of MVs as effective drug carriers and agents that can enhance therapeutic outcomes by modulating the immune response and intestinal microbiota. This highlights their significant potential in the development of innovative oral drug delivery systems (Huang, Zhang, et al., 2024).

2.3. Source of plants

2.3.1. Pollen

Pollen, a naturally occurring substance characterized by uniform micrometre-scale dimensions, possesses structural features conducive to its application as hollow microcapsules, microgels, and composites. These applications span various fields, including drug delivery, sensing, and bioabsorption. The porous nature and inherent fluorescence properties of pollen enhance its functionality as a drug delivery carrier, offering efficient drug protection, targeted release, minimised side effects, and improved therapeutic efficacy (Ourani-Pourdashti & Azadi, 2021). Consequently, pollen demonstrates significant potential and advantages in the realm of medical applications.

2.3.1.1. Sunflower pollen

Sunflower pollen is distinguished by its intricate three-dimensional structure, featuring spikes and nanopores that collectively provide a substantial specific surface area and numerous adsorption sites. This structure is particularly effective for the adsorption of drugs and the encapsulation of gases, facilitating the simultaneous transport of gases and pharmaceutical agents (Wen et al., 2023). Deng et al. (2021) developed a probiotic protection system using sunflower pollen extract outer wall capsules (SECs) combined with calcium alginate (Alg)/carboxymethyl poria polysaccharide (CMP) composite gel to encapsulate Lactiplantibacillus plantarum. Through a core-shell structure design (SECs as the core and Alg/CMP gel as the shell), the system achieved a high bacterial loading capacity of 1.17 × 10¹⁰ CFU/g, significantly enhancing microbial stability. The lyophilised product retained 85.7 % viable bacteria post-freezing, and maintained a live bacterial concentration of 2.09 × 10⁶ CFU/mL even after 90 days of storage at 4 °C. The delivery pathway demonstrated precise controllability, achieving zero leakage in simulated gastric fluid and sustained release for over 8 h in intestinal environments, ultimately delivering >10⁷ CFU/mL of active probiotics to the large intestine. In another innovative application, sunflower pollen was employed as an oral drug delivery vehicle for the treatment of gastric ulcers (Cai et al., 2024). Leveraging the unique spinous structure and autonomous motility of the pollen, it actively navigated within the stomach and adhered to the gastric mucosa, significantly extending the drug's residence time in the stomach and thereby enhancing drug bioavailability. Moreover, the internal cavity structure of the pollen provided excellent drug loading and release capabilities. Experimental results indicated that sunflower pollen micromotors loaded with berberine achieved significantly superior therapeutic outcomes in a mouse model of gastric ulcers compared to the administration of free drugs.

2.3.1.2. Pine pollen

Pine pollen is a nutrient-rich natural resource, abundant in proteins, vitamins, and carbohydrates, and exhibits a range of biological activities (Tao et al., 2024). Pine pollen had a complex structure with dual air sacs and a central cavity. The air sacs and the porous outer wall accounted for one-third and one-fifth of the total volume, providing a large loading capacity. After acid treatment to remove the contents, the remaining exine wall of the pollen had high mechanical strength and chemical stability, making it suitable for drug encapsulation. Additionally, the outer wall of pine pollen contained hydroxyl groups, aromatic chains, and fatty chains. These functional groups gave it excellent adsorption capacity for polar molecules, such as polyphenolic compounds, allowing it to adsorb drug molecules through hydrogen bonding or hydrophobic interactions (Cheng et al., 2023).

Due to its unique structural and biological properties, pine pollen has shown its potential as a drug delivery system. Li, Song, et al. (2024) developed a novel microcapsule technique based on pine pollen. The pine pollen was processed with phosphoric acid to form the microcapsules with a natural core-shell structure (named as PPS), which exhibited better hydrophobicity and lipophilicity. In vitro studies showed that PPS remained stable in simulated gastrointestinal fluids. In vivo studies further demonstrated that PPS maintained good biosafety, with no significant tissue damage or inflammatory response after long-term oral administration.

2.3.2. Plant-derived polysaccharides

Plant-derived polysaccharides are not only metabolizable by the intestinal microbiota, which convert them into metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters, but they also synergistically interact with probiotics to enhance their survival and effectiveness in the gastrointestinal tract. These interactions regulate the composition and activity of the intestinal microbiota. Consequently, plant-derived polysaccharides possess significant potential as natural active carriers in functional foods and drug delivery systems (Liu, Shi, et al., 2024).

2.3.2.1. Inulin

Inulin (INU), a naturally occurring polysaccharide, is predominantly found in the roots and tubers of certain plants, including the Jerusalem artichoke and chicory. Through fermentation, INU can produce SCFAs, which play crucial roles in regulating intestinal flora, enhancing intestinal barrier function, and exerting immunomodulatory effects. Additionally, INU serves as a sustainable and controlled drug release medium, thereby improving the bioavailability of pharmaceuticals (Akram et al., 2024). Consequently, INU is recognized not only as an outstanding prebiotic, but also as a versatile drug carrier, offering new avenues for personalized and targeted therapeutic strategies.

The progression of IBD is closely associated with excessive production of ROS, primarily stemming from mitochondrial damage in host cells and dysbiosis of gut microbiota. However, bacteria predominantly colonize the “outer” side of the colon lumen and epithelial cells (the luminal surface), ROS generation originates from the “inner” side of host cells (macrophages and colonic epithelial cells). This spatial separation severely limits synchronised precision intervention of both pathogenic mechanisms (microbiota and host cells). To address this issue, Xing et al. (2024) developed an oral graded-targeted delivery platform. By integrating natural antioxidants resveratrol and dietary prebiotic inulin, this platform achieved coordinated regulation of gut microbiota remodelling and host cell mitochondrial function through temporal control and spatial positioning, thereby providing a novel multi-target therapy strategy for IBD. Furthermore, an INU-based nanomicellar drug delivery system has been developed to combat Salmonella infection (Xu, Niu, et al., 2024). This system facilitated the rapid release of levofloxacin at sites of intestinal inflammation and selectively targeted intestinal pathogens. Concurrently, INU, as a prebiotic fibre, improved populations of Bifidobacteria and lactic acid bacteria in the intestinal tract of mice, supported the maintenance of the intestinal mechanical barrier, and helped regulate the balance of intestinal flora.

2.3.2.2. Chitosan

Chitosan, a natural polysaccharide, has demonstrated significant potential as a drug carrier due to its distinctive physicochemical properties, biocompatibility, biodegradability, and ability to adhere to the gastrointestinal mucosa, particularly beneficial in the treatment of IBD (Liu, Fu, et al., 2024). Sahar et al. (2025) used chitosan to design the lipid core-chitosan hybrid nanoparticles for the delivery of sorafenib, substantially enhancing the oral bioavailability of this drug. The nanoparticles were stabilsed by an electrostatic coating of chitosan over the lipid core, which not only extended the drug release duration but also strengthened the interaction between the nanoparticles and the gastrointestinal mucosa, thereby improving the absorption efficiency of sorafenib. In oral administration studies in rats, these chitosan-coated nanoparticles showed a significant increase in the area under the curve (AUC) and maximum plasma concentration (C_max) of sorafenib, approximately 3.9 times and 4.2 times greater, respectively, compared to uncoated sorafenib dispersion and lipid-core nanoparticles.

Additionally, a chitosan-modified polylactic acid-glycolic acid (PLGA) nanomedicine (CS-PIPP) encapsulating Sanghuang polyglycan (PIP) was developed by using chitosan-modified PLGA as a carrier. This modification not only enhanced the bioavailability and mucosal penetration of PIP but also increased the local drug concentration through the positive charge interaction with the negatively charged intestinal mucosa. It should be noted that chitosan modification enhanced the stability of the drug, exhibiting potent anti-inflammatory effects in both in vitro and in vivo experiments. In DSS-induced mouse models of IBD, CS-PIPP significantly mitigated intestinal inflammation, regulated dysbiosis of intestinal microbiota, and preserved the integrity of the intestinal barrier by increasing the levels of SCFAs (Bai et al., 2022).

2.3.2.3. Pectin

Pectin, a naturally occurring anionic polysaccharide predominantly extracted from the cell walls of plants such as citrus and apples, contains abundant carboxylic acid groups. These functional groups enable pectin to maintain a dense structure in the acidic environment of the stomach, thereby protecting encapsulated active components. In the neutral to weakly alkaline conditions of the intestine, pectin facilitates the swelling of gels and the precise release of drugs through electrostatic repulsion. This property makes it particularly suited for targeted therapy of intestinal diseases such as UC. Currently, pectin is extensively utilised in developing oral colon-targeted formulations, controlled-release microspheres, and nano-delivery systems (Kapoor et al., 2024).

Pectin can promote the absorption and utilisation of drugs in the colon, improve drug bioavailability and distribution in the colon, and thus amplify the therapeutic efficacy of intestinal disorders. For example, the development of FA/CUR-PEG-LPs@PC drug delivery systems involved embedding folic acid-modified curcumin liposomes within pectin-chitosan hydrogels (PC), which were tailored to target colon macrophages via oral administration (Wu et al., 2023). Pectin's unique physicochemical properties allowed it to effectively encapsulate and protect curcumin, ensuring its stability throughout the gastrointestinal tract and specific release at the colonic site. This targeting ability of FA/CUR-PEG-LPs@PC improved the drug's efficacy and minimised side effects. Additionally, targeted therapy for UC might also be facilitated through the construction of an OMT/SA-NPs system, which involves the encapsulation of oxymatrine in nanoparticles to create a stable, controlled-release drug delivery system (Liu, Dong, et al., 2024). This system was characterized by its stability and controlled release capabilities in the gastrointestinal tract, enabling targeted drug delivery to the colon, thereby enhancing drug efficacy and reducing side effects.

2.3.2.4. Konjac glucomannan

Konjac glucomannan's molecular configuration endows it with multiple functions, such as high viscosity characteristics, remarkable hydration ability, thermal reversible/irreversible gel formation ability, and excellent film formation and biocompatibility. These characteristics make it an ideal carrier for bioactive substances in the food industry, which can efficiently realise the packaging, protection and targeted delivery of active ingredients (Zhang, Tong, et al., 2024). Furthermore, Liu, Su, et al. (2024) used deacetylated konjac glucomannan as a microcarrier, proanthocyanidins (PC) was loaded through physical encapsulation, so as to solve the degradation problem of PC in the gastrointestinal tract and realise targeted colon delivery (76.76 % of PC can reach the colon). The system not only improved the bioavailability and stability of PC, but also promoted intestinal microecological balance through probiotic effects and antioxidant synergies, providing innovative strategies for functional food and disease prevention.

2.4. Source of microbes

2.4.1. Ganoderma lucidum spores

Ganoderma lucidum spores (GLSs), the reproductive units of Ganoderma lucidum, are distinguished by their ovoid, spindle-like structure, which includes dual wall layers and a large internal chamber with numerous natural pores on the surface. Owing to their distinctive physical and chemical characteristics, these spores are regarded as promising carriers for oral drugs and vaccines. GLSs could be engineered into porous carriers with selective affinity, capable of efficiently delivering various drugs, including hydrophilic drugs like methylene blue (MB) and lipophilic drugs like rifampicin (RF) (Liao et al., 2023). The drug delivery capabilities of these engineered spores were influenced by the hydrophilic or lipophilic nature of the targeted drugs. These GLS carriers demonstrated substantial adhesion and prolonged retention in the gastrointestinal mucosa in animal models, enhancing mucus secretion and the expression of intestinal barrier proteins, thereby providing an effective platform for the treatment of gastrointestinal disorders. Besides, GLSs were engineered into magnetic carriers (mGLS) for the delivery of 5-fluorouracil (5-FU), a chemotherapeutic agent. This study showcased the sustained-release properties of the engineered spore carriers both in vitro and in vivo, underscoring their potential utility in treating gastrointestinal-related diseases (Han et al., 2021).

2.4.2. Yeast cell wall

Yeast is the first single-celled eukaryotic organism for which genome sequencing has been completed. Its distinctive biological characteristics render it an exemplary carrier for drugs and vaccines (Fig. 2). Yeast β-glucan is a kind of functional polysaccharide widely spreading in the cell wall of yeast, which is capable of being absorbed by intestinal M cells through oral ingestion, subsequently entering the lymphatic system to facilitate targeted delivery of active substances. Recent advancements have highlighted the extensive potential of yeast-based drug delivery systems and vaccine vectors across various medical fields. These include oncology, infectious disease management, chronic inflammation treatments, and the development of veterinary vaccines, offering innovative approaches for new drug delivery methodologies and vaccine innovation (Tan et al., 2022).

Fig. 2.

Types and properties of natural active carriers and their intervention for intestinal diseases.

Traditional delivery carriers of bioactive substances often face limitations such as diverse material types, complex processes, and insufficient targeting capabilities. To address these challenges, Yao et al. (2025) developed a yeast membrane-based nanodelivery system called YMS@MBP for delivering polyphenols from Schisandra chinensis (MBP). This system fully utilised the acid-stable properties of β-glucan and its enzymatic responsiveness in yeast membranes. The results showed that only 16.04 % of polyphenols were released in gastric fluid, while achieving explosive release (up to 79.39 %) in the intestinal phase through precise enzymatic response. Additionally, Li, Sun, et al. (2024) ingeniously constructed a drug delivery platform based on a metal polyphenol network (MPN) by incorporating curcumin (Cur) into the MPN to create Cur-MPN, which was then encapsulated within yeast microcapsules (CM@YM). The CM@YM system not only protected the Cur from gastric acid, but also enhanced its targeting and retention in the intestinal tract. This system substantially reduced symptoms of UC by scavenging ROS, regulating the gut microbiota, and suppressing inflammatory responses, thus demonstrating the significant potential of yeast microcapsules as natural active carriers in the management of intestinal diseases. Altogether, these data suggested that both of these drug delivery systems exploited the unique properties of yeast microcapsules, combining various drugs and therapeutic approaches to achieve marked efficacy and benefit to prevent the development of intestinal diseases.

3. Fabrication strategies of food-derived delivery systems

3.1. Freeze drying-rehydration technology

Freeze-drying-rehydration technology integrates a series of processes that entail the removal of water at low temperatures, followed by the restoration of the material's original form and function through rehydration. The initial phase involves the rapid freezing of the sample at extremely low temperatures, typically ranging from −40 °C to −80 °C. This is succeeded by the sublimation process, which occurs in a vacuum environment to remove water, thereby preserving the microstructure and active components of the material (Antal, 2021). The subsequent phase involves the reabsorption of water into the desiccated product using water or other solvents, effectively restoring its physical form, such as a porous structure, and its functional properties, including drug release characteristics (Zhang et al., 2023). As depicted in Fig. 3, Zhong et al. (2021) employed SP for encapsulating the hydrophobic drug curcumin through a method of freeze-drying followed by rehydration. Initially, SP was mixed with a curcumin solution to facilitate drug loading via a straightforward stirring process, which was subsequently followed by centrifugation to collect curcumin-loaded SP (SP@Curcumin). To ensure the stability of the drug load and to enhance its storage convenience and application, the SP@Curcumin suspension was frozen and lyophilised to produce a stable, dry powder. This lyophilised powder not only offers the advantage of extended shelf life but also can be readily rehydrated in deionised water. Using this technique, SP was effectively loaded with curcumin, which demonstrated significant protection of the drug and sustained release properties in simulated gastric and intestinal fluids, thereby improving the oral bioavailability and therapeutic efficacy of curcumin.

Fig. 3.

Schematic representation of constructing food-derived delivery systems via freeze drying-rehydration technology (A), ionic crosslinking (B) and electroporation (C).

3.2. Ionic crosslinking

Ionic crosslinking represents a physical crosslinking technique that establishes a three-dimensional network structure via electrostatic interactions between multivalent ions and charged biopolymers. The fundamental principle involves the use of oppositely charged ions as “bridging agents” to interact with functional groups on polymer chains, such as carboxylate and amino groups, thereby facilitating the formation of stable gels or nanoparticles. This method is extensively employed in the modification of natural polymers, including chitosan and alginates, and is particularly effective for the construction of drug delivery carriers (Wurm et al., 2020).

The scientists utilised the inherently negative charge of the C. vulgaris (CV) surface to effectively adsorb positively charged insulin (INS) via electrostatic interactions in an acidic environment (pH = 3), resulting in the formation of CV@INS complexes (Ren et al., 2023). Following this, the insulin-loaded microalgae were combined with sodium alginate (ALG) and crosslinked using Ca²⁺ to create an “egg-carton” structure, culminating in the development of a pH-responsive hydrogel, termed CV@INS@ALG, through ion crosslinking technology. This dual-layer delivery system not only preserved the natural biological activity of the microalgae but also provided gastric acid resistance for insulin (with only 22.06 % release) and facilitated a controlled release in the alkaline conditions of the intestines (releasing 96.92 % of the insulin within 12 h). This system employed a dual absorption mechanism involving microalgae-mediated M cell endocytosis and macrophage phagocytosis.

Additionally, Joseph et al. (2024) developed a colon-targeted drug delivery system based on ion crosslinking. Initially, 0.5 % (w/v) inulin (INU) was dissolved in 5 mL of ultrapure water containing 1 % (v/v) honey to prepare a polymer solution. Subsequently, irinotecan hydrochloride trihydrate (IHT) was incorporated at a polymer-to-drug ratio of 10:1 for drug encapsulation. Then, 1 mL of 1.25 % (w/v) calcium chloride solution was gradually added as a crosslinker. The resultant mixture was then filtered through a 0.45 μm filter membrane and lyophilised to obtain the drug-loaded INU nanoparticles (IINPs). This method prevents particle aggregation, which is often exacerbated by the proteins and monosaccharides in honey, and leverages Ca²⁺-INU ion crosslinking to develop pH-responsive nanocarriers that effectively target drug release in the colonic environment.

Similarly, Zhao, Jia, et al. (2024) developed an OMT/SA-NPs system utilising a combination of ion crosslinking and chemical conjugation techniques. Initially, sialic acid (SA) and chitosan (CS) were conjugated through a reaction catalysed by 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The reaction products were then purified via dialysis, lyophilised, and successfully attached to the CS chain. Following this, nanoparticles were synthesised through ion crosslinking. A drug solution (0.375 g/L) was prepared by dissolving an appropriate amount of oxymatrine (OMT) in a 0.2 g/mL calcium chloride solution. The solution was slowly added to a 0.75 g/L pectin solution and thoroughly mixed. Under constant stirring at 37 °C, a 0.5 g/L SA-CS solution was gradually added dropwise to the mixture containing pectin and OMT, with continuous stirring for 2 h. The final product was freeze-dried OMT/SA nanoparticles. The resulting carrier system forms a three-dimensional network structure using calcium ions to crosslink pectin, with an outer layer encapsulated by SA-CS. This configuration facilitates targeting of the Siglec-9 receptor on macrophage surfaces. The system demonstrated sustained drug release under simulated colonic pH conditions, thereby confirming its targeting capability and stability within the colon.

3.3. Electroporation

Electroporation employs controlled high-voltage pulses to temporarily enhance cell membrane permeability through nanoscale pore formation. This non-thermal, energy-efficient method enables precise transport of bioactive macromolecules (nutraceuticals, enzymes, or genetic material) while maintaining cellular integrity. Its versatility supports nutrient encapsulation, probiotic stabilisation, and bioactive delivery in complex matrices. Recent innovations in pulse modulation and electrode design enhance compatibility with sensitive biomolecules, improving bioavailability and controlled release (Feng et al., 2022). Cui et al. (2024) utilised electroporation to successfully incorporate tetrahedral framework nucleic acids (tFNAs), which were modified with antimicrobial peptides (AMP), into exosome-like nanovesicles derived from ginger, resulting in the formation of Exo@tac complexes. In the process, they combined tFNAs with exosome-like nanovesicles at a volume ratio of 1:400 and subjected this mixture to electroporation at temperatures ranging from 20 °C to 25 °C using the Gene Pulser Xcell device (0.7 kV, 350 μs, 20 pulses). Following electroporation, the mixture was incubated at 37 °C for 30 min to facilitate the formation of complexes. The characteristics of Exo@tac, including morphology, size, and concentration, were assessed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The findings indicated that Exo@tac was stable and resistant to acidic environments, maintaining its integrity in gastric acid. This stability was crucial for its effectiveness in modulating the intestinal microbiota and alleviating the symptoms of Parkinson's disease following oral administration.

3.4. Ultracentrifugation

Ultracentrifugation leverages ultrahigh centrifugal forces (>100,000 ×g) to achieve high-precision separation and analysis of complex biological samples. Its core principle relies on differential sedimentation rates of components (organelles, proteins, nucleic acids) based on density, molecular weight, and particle morphology. This non-destructive, scalable technique enables efficient purification and stratification of food-derived biomolecules while preserving their structural and functional integrity (Dash et al., 2021). For example, L. plantarum was subjected to a 24 h treatment with lysozyme to remove peptidoglycan from the cell wall and obtain protoplasts. This was followed by the release of cell membrane components through sonication disruption and the subsequent purification of membrane fragments by gradient centrifugation. These membrane fragments were then reassembled into nanoscale membrane vesicles (SyMVs) through gentle sonication (35 kHz, 30 min) in PBS. To encapsulate fucoxanthin (FX), the membrane fragments were combined with FX in a 1:1 mass ratio, and excess components were removed by ultracentrifugation (100,000 g) after ultrasonic loading. This process resulted in the formation of FX-loaded membrane vesicles (FX-MVs) (Liang et al., 2023). This engineered preparation strategy not only increased the yield of membrane vesicles by 150 times but also significantly enriched the membrane protein components, thereby providing a novel carrier system for the efficient delivery of hydrophobic active ingredients.

3.5. Acid-base degreasing method

Acid-base degreasing utilities controlled acidic or alkaline solution to selectively remove organic templates, residual impurities, or modulate the surface/pore architecture of materials. The tailored pore configuration not only enhances the carrier's drug-loading capacity but also establishes a structural foundation for post-functionalization, such as stimuli-responsive coatings. As described in Fig. 4, Wang et al. (2024) employed natural sunflower pollen as a substrate, subjecting it to a combined treatment of acetone degreasing, KOH alkalinolysis, and phosphoric acidolysis. This process removed inherent pollen components, resulting in the formation of a porous spore wall capsule (SEC). Subsequently, dopamine was polymerised on the surface of the SEC, creating a polydopamine (PDA) coating that enhanced adhesion properties and facilitated the immobilisation of thrombin. Using the porous structure of SEC and the strong adsorption capacity of PDA, dexamethasone (Dex) was encapsulated in the capsule by physical loading, while thrombin was combined by chemical bonds to form polydopamine-coated sporopollenin microcapsules loaded with thrombin and dexamethasone (PS (t + Dex)). Ascorbyl palmitate (AP) was then applied to the surface of PS (t + Dex) through physical deposition technology to produce an AP@PS (t + Dex) intermediate layer with enzyme-responsive characteristics. The final layer involved coating a pH-sensitive Eudragit L100–55 (EL) polymer membrane uniformly over the AP layer via solvent evaporation, resulting in an EL/AP@PS (t + Dex) composite carrier. This system integrated the adhesive properties of natural pollen, the biocompatibility of PDA, the enzyme-responsive cleavage properties of AP, and the intestinal pH-responsive release characteristics of EL. Through sequential functional modifications, the system achieved dual-targeted, controlled drug release at sites of inflammation.

Fig. 4.

Schematic representation of constructing food-derived delivery systems via ultracentrifugation (A), acid-base degreasing method (B) and emulsification-curing method (C).

Furthermore, Han et al. (2021) initiated their study by treating natural GLS with spore cavitation, followed by a defatting process using acetone reflux at 70 °C for 24 h. The spores were then immersed in an 18 % KOH solution for 24 h to remove cellulose from the inner wall and treated with 85 % phosphoric acid at 70 °C for 12 h to enlarge pore structures, ultimately yielding a hollow porous configuration. Following this, a mixed solution of Fe³⁺/Fe²⁺ (comprising 5 M HCl and ethanol) was combined with the cavitated spores and subjected to vacuum infiltration under a negative pressure of −0.1 MPa at 40 °C for 15 min. The addition of ammonia triggered a co-precipitation reaction over 2 h, resulting in the in situ deposition of Fe₃O₄ nanoparticles on both the internal and external surfaces of the spores. The mGLS was then isolated via magnetic separation, washed, and dried. Finally, mGLS was combined with a 5-fluorouracil (5-FU) solution under negative pressure for 2 h using vacuum loading technology. The drug delivery system (5-FU@mGLS) was then obtained through centrifugal separation, employing the porous structure of the spores. This methodology integrated chemical etching, in-situ synthesis of magnetic nanoparticles, and vacuum penetration technology to successfully establish a natural drug carrier system featuring both magnetic targeting and sustained-release capabilities.

3.6. Metal-phenolic networks

Metal-phenolic networks (MPNs) are coordination-driven assemblies formed between metal ions and phenolic ligands under mild conditions. These nanomaterials exhibit inherent biocompatibility and biodegradability, alongside tunable biological activities such as antioxidant, anti-inflammatory, and antimicrobial effects. Their chemical versatility enables precise customisation of functionality (stimuli-responsive behaviours or enhanced stability) by modulating ligand structures or metal ion species (Rong et al., 2025). Li, Sun, et al. (2024) employed MPNs technology, which constructed MPNs through the coordination of epicatechin (EGCG) and iron ions (Fe³⁺). Curcumin, known for its anti-inflammatory properties, is then self-assembled into the MPN to create Cur-MPN. This process not only enhanced the bioavailability of curcumin but also amplified its antioxidant and anti-inflammatory effects. Following this, Cur-MPN was encapsulated within yeast microcapsules (YM) via chemical precipitation. YM was primarily composed of β-glucan, which interacted with the Dectin-1 receptor on macrophages, facilitating targeted delivery to inflammation sites. Additionally, the mannan content in YM served as a prebiotic, fostering the growth of beneficial bacteria, inhibiting harmful bacteria, and modulating the intestinal flora structure. The resultant CM@YM system effectively shielded Cur-MPN from gastric acid degradation and strategically released the drug in the intestine for UC treatment. Through this multifaceted mechanism, the CM@YM system has demonstrated substantial efficacy in alleviating colitis.

3.7. Emulsification-curing method

Emulsification curing involves stabilising oil-in-water (O/W) emulsions via emulsifiers, followed by cross-linking reactions to synthesise porous materials with tunable pore architectures. This technique enables precise control over matrix porosity and surface functionality, enhancing bioactive encapsulation efficiency and controlled-release kinetics (Jie et al., 2024). For instance, Sun et al. (2025) utilised an evaporation technique with a water-in-oil (O/W) emulsion. Budesonide and carboxylated poly(lactic-co-glycolic acid) (PLGA) were dissolved in a methanol-chloroform mix (1,3 ratio) at a mass ratio of 1:30. This solution was then gradually added to an aqueous phase containing 1 % polyvinyl alcohol (PVA) to form an emulsion. The emulsion underwent ultrasonic treatment at 400 W for 10 min, followed by overnight magnetic stirring to evaporate the solvent. Subsequently, spherical nanoparticles of approximately 300 nm in diameter were produced through centrifugation and lyophilisation. These nanoparticles underwent an alkaline-acid treatment, where yeast powder was treated with 1 M NaOH at 80 °C for 1 h and 1 M HCl at 60 °C for 1 h. The intracellular substances were then removed by centrifugation, yielding hollow microcapsules of about 2700 nm, composed of β-glucan and polysaccharides. Subsequently, the budesonide-loaded PLGA nanoparticles (NPs) and yeast microcapsules (YPs) were treated in a 1:1 volume ratio, and mixed in Na₂CO₃ solution overnight at room temperature. Subsequently, the solution was processed through a liposome extruder with a 1 μm pore size to form NPs-YPs complexes (NYPs) with a size of approximately 3100 nm. Finally, an aqueous 8 % pectin solution was mixed with the NYPs suspension and crosslinked with a 6 % CaCl₂ solution under magnetic stirring to form a pectin gel with a three-dimensional network structure. This resulted in the creation of a NYPs@Gel composite delivery system, designed for intestinal targeting and sustained release.

4. The bioactive potentials of food-derived micro-nano delivery platforms in intestinal disorders

4.1. Anti-inflammatory effects

Recent research into natural active carrier systems has revealed that through innovative drug delivery platforms, these systems not only enhance the bioavailability of therapeutic agents but also specifically target inflammatory pathways. This targeting facilitates a marked enhancement in anti-inflammatory responses. For instance, the SP-curcumin delivery system (SP@Curcumin) has demonstrated pronounced anti-inflammatory properties primarily by diminishing the production of pro-inflammatory cytokines, such as TNF-α and IL-6 in colitis models (Zhong et al., 2021). This reduction inhibited inflammatory responses effectively. Compared to curcumin alone, SP@Curcumin has shown superior capabilities in scavenging ROS, further mitigating inflammation within the body. Furthermore, milk EVs exhibited notable anti-inflammatory effects. They regulated the expression of genes associated with intestinal stem cells by transporting specific microRNAs (miRNAs), including miR-29 and miR-34a, which accelerated the regeneration of intestinal epithelial cells and promoted the repair of damaged intestinal epithelium. These vesicles also enhanced gut health by modulating the gut microbiota composition and boosting the immune response within the gut. It should be noted that milk EVs contributed to the reduction of intestinal inflammation by suppressing the expression of inflammation-related genes and decreasing the levels of inflammatory cytokines such as TNF-α and IL-6 (Wang et al., 2024).

4.2. Antioxidation

In recent years, the interest in active substances derived from natural sources has grown significantly due to their excellent biocompatibility and diverse biological effects. Natural carriers not only facilitate the delivery of active ingredients but also bolster the body's antioxidant defences through various mechanisms, thereby offering potential therapeutic benefits as antioxidants. As shown in Fig. 5, the FX-MVs vector system designed by Liang et al. (2023) has demonstrated significant antioxidant effects in the treatment of inflammatory bowel disease (IBD). Results showed that FX-MVs could effectively inhibit the oxidative damage induced by H₂O₂ and significantly improve the antioxidant capacity of cells by scavenging free radicals. FX-MVs significantly enhanced the total antioxidant capacity (T-AOC) and glutathione (GSH) levels, while reducing the malondialdehyde (MDA) content and decreasing the production of intracellular reactive oxygen species (ROS) levels in vitro. In in vivo experiments, FX-MVs significantly increased T-AOC and GSH levels in colon tissues, reduced the levels of nitric oxide (NO), myeloperoxidase (MPO) and epoxygenase-2 (COX-2), and effectively inhibited the secretion of proinflammatory cytokines (TNF-α and IL-6), while increasing the secretion of anti-inflammatory cytokines IL-10.

Fig. 5.

(A) Potential therapeutic mechanism of CM@YM (Li, Sun, et al., 2024). (B) Targeted therapy mechanism of FA/CUR-PEG-LPs@PC for UC (Wu et al., 2023). (C) Mechanism of oral FX-MVs treatment for colitis. (D) Schematic diagram of oral OMT/SA-NPs treatment for UC in mice (Zhao, Jia, et al., 2024). (E) Nanobeads based on inulin were used for the treatment of H₂S-triggered salmonella infection (Xu, Niu, et al., 2024). The IUN released after dissociation could promote the proliferation of bifidobacterium and lactic acid bacteria and maintain the integrity of the mechanical barrier.

4.3. Immunomodulation

Recent advancements have significantly enhanced our understanding of the immunomodulatory roles of natural active carriers. These natural active carriers, through their inherent biomaterial properties, not only improve the immune response but also effectively mitigate cellular damage inflicted by free radicals, leveraging their distinctive antioxidant characteristics. For instance, Saccharomyces cerevisiae, a natural carrier, exhibited not only immunomodulatory capabilities but also served as a critical platform for both antioxidant therapy and immunotherapy due to its abundant surface β-glucan. The β-glucan present on the surface of Saccharomyces cerevisiae facilitated the phagocytosis of yeast and activated the immune response by specifically binding to the Dectin-1 receptor on antigen-presenting cells, including dendritic cells (DCs) and macrophages. Further research has demonstrated that the targeted deletion of genes associated with the inhibition of dextran synthesis, through genetic engineering techniques, could increase the dextran levels on the yeast surface. This enhancement strengthened the interaction between the yeast and antigen-presenting cells, thereby amplifying the immunological effectiveness of yeast-based vaccines. Moreover, co-expression technologies involving the fusion of chicken ovalbumen and small interfering RNA have been employed to refine the immunogenicity of the yeast vector, rendering the recombinant yeast more effective in promoting antigen presentation and eliciting specific immune responses (Han, Yue, et al., 2024). Collectively, these strategies position Saccharomyces cerevisiae as a promising oral vaccine vector, capable of bolstering host immune defences while avoiding the induction of additional immunotoxicity.

4.4. Regulation of microbial communities

The microbial community within the gastrointestinal tract constitutes a highly complex and dynamically balanced ecosystem, the composition and function of which are crucial for maintaining the host's health. Gut microbes are involved not only in the digestion and absorption of nutrients but also in influencing immune responses, metabolic processes, and the pathogenesis and progression of diseases through their metabolites and immunoregulatory activities. Recent research increasingly supports the notion that natural active compounds, such as prebiotics, can positively influence host health by modulating the composition and functionality of the gut microbial community. In this vein, INU, a biosafe fructan and effective prebiotic, enhanced the populations of bifidobacteria and lactic acid bacteria in the murine intestinal tract. This increase supported the maintenance of the intestinal mechanical barrier and helped regulate the balance of the intestinal flora. Such modulation was instrumental in restoring intestinal health, fostering the growth of beneficial microbes, curbing the proliferation of detrimental ones, and ameliorating symptoms of intestinal inflammation (Xu, Niu, et al., 2024). Furthermore, INU could selectively enhance the activity and proliferation of intestinal bacteria that benefited host health through its fermentation in the gut. These probiotics contributed positively to the management of IBD by promoting nutrient metabolism, inhibiting pathogenic growth, maintaining the structural integrity of the intestinal barrier, and regulating intestinal homeostasis.

Additionally, EVs also play a therapeutic role by modulating the intestinal microbiota. Initially, EVs enhanced the microbial diversity and abundance of intestinal organisms and ameliorated the intestinal microecological environment by delivering essential nutrients and growth factors. Subsequently, by suppressing the growth of pathogenic bacteria, EVs released antimicrobial substances such as peptides, which decreased the activity of pathogenic bacteria and reduced both the severity and frequency of intestinal inflammation, thus playing a pivotal role in the management of IBD (Li, Luo, et al., 2025).

4.5. Intestinal barrier repair

Natural plant polysaccharides have many significant advantages as natural active carriers for intestinal barrier repair. First, by regulating the diversity and abundance of intestinal flora, they promote the proliferation of beneficial bacteria and inhibit the growth of harmful bacteria, thus improving the intestinal microecological environment and creating favourable conditions for the repair of the intestinal barrier. Secondly, natural plant polysaccharides can interact with the intestinal epithelial cells, promote the expression of tight junction proteins, enhance the tight junctions between intestinal epithelial cells, and thus improve the integrity of the intestinal barrier. In terms of biosafety, natural plant polysaccharides also have good biocompatibility and biodegradability, and can be fermented by intestinal microorganisms to produce short-chain fatty acids and other beneficial metabolites, further promoting intestinal health (Yang et al., 2022). For example, nanoparticles co-assembled by rhubarb polysaccharide and berberine (BD) could regulate the intestinal flora, increase the relative abundance of beneficial bacteria such as Lactobacillus, and restore the balance of the intestinal flora, thus reducing the production of inflammatory factors. BD also significantly upregulated the expression of tight junction proteins (such as occludin and zonula occludens-1), enhanced the tight junctions between intestinal epithelial cells, and repaired the integrity of the intestinal barrier. In addition, BD was able to promote the conversion of M1 macrophages to M2 macrophages, reducing the levels of the proinflammatory cytokine TNF-α, while increasing the expression of the anti-inflammatory cytokine Arg-1, thereby alleviating the intestinal inflammatory response (Feng et al., 2023). Similarly, Zhao, Jia, et al. (2024) developed a nanoparticle modified by sialic acid (SA) to load the drug Oxymatrine (OMT) to achieve oral targeted therapy for UC.

5. Advantages of food-derived delivery platforms for gastrointestinal delivery

5.1. Biocompatibility

The selection criteria for natural active carriers primarily encompass biocompatibility, controllable enzyme degradation, specific interactions with biomolecules, and ease of modification. These criteria enable natural polymers, such as polysaccharides and proteins, to exhibit extensive potential in DDS. The primary advantage of natural active carriers lies in their derivation from biomaterials, often ensuring biocompatibility and biodegradability, which minimises the patient's immune response and toxicity risk. Additionally, their structural similarity to the body's extracellular matrix contributes to the minimal invasiveness of these drug carriers (Tong et al., 2020) (Fig. 6).

Fig. 6.

Comparison of bioavailability from traditional delivery carriers to natural active carriers.

5.2. Bioavailability

Natural active carriers employ a variety of mechanisms to regulate drug release rates and enhance bioavailability. Leveraging their unique physicochemical properties and structural characteristics, these carriers protect drugs from damage by metabolic enzymes and the gastrointestinal environment. This protection extends the circulation time of drugs within the body and promotes drug accumulation at targeted lesion sites. Through chemical modifications and structural adjustments, these carriers can respond to specific physiological stimuli, such as pH changes, enzyme activity, temperature, and light, enabling controlled drug release. This not only reduces side effects but also improves therapeutic efficacy (Zhao, Yang, et al., 2024).

5.3. Multi-targeting and synergism

This property of naturally active carriers in terms of multiple targets and synergistic performance gives it significant potential for improving therapeutic efficacy and enhanced bioavailability. For instance, plant-derived exosome-like nanoparticles (PELN) were natural nanocarriers that exhibited multi-target effects in colon cancer therapy (Yi et al., 2025). On the one hand, they could prevent the occurrence and progression of cancer by regulating intestinal homeostasis and inflammatory response. On the other hand, miRNAs carried by PELNs directly targeted key genes and signalling pathways in cancer cells to inhibit the proliferation, migration and invasion of tumuor cells and induce apoptosis of tumuor cells, thus exerting anticancer effects. Therefore, PELNs could serve as drug carriers to deliver therapeutic molecules to the tumuor site for the improvement of therapeutic effects and the reduction of side effects.

In another study, resveratrol-loaded sulphated herthiens β-dextran-chitosan nanoparticles (DS-CS-RES NPs) were prepared by electrostatic self-assembly by Zhang, Ge, et al. (2024). DS-CS-RES NPs and resveratrol (RES) had synergistic anti-inflammatory effects, which significantly inhibited the production of IL-1 β, IL-6, and TNF-α, better than DS-CS NPs or resveratrol alone. The results of western blot experiments showed that DS-CS-RES NPs regulated the protein expression of NF-κB p65, STAT 1 and TLR 4 through NF-κB and JAK-STAT1 signalling, thus exerting anti-inflammatory effects. Moreover, flow cytometry analysis showed that DS-CS-RES NPs were able to promote the transformation of M1-type macrophages into M2-type macrophages with anti-inflammatory effects.

5.4. Prolonged intestinal retention

Within the gastrointestinal tract, the duration of residence of natural active carriers significantly impacts the efficacy of drug delivery, especially for drugs that require sustained release or targeted action at specific sites. For instance, the biocompatibility and nanoscale size of chitosan enable it to evade rapid in vivo clearance mechanisms, such as phagocytosis by the reticuloendothelial system. Moreover, the surface properties of chitosan can be modified chemically to enhance its accumulation and retention in tumuor tissues. This prolonged residence time not only facilitates the sustained release of the drug but also increases its local concentration, thereby enhancing the therapeutic effect. Not only that, it minimises the distribution of the drug in normal tissues, reducing potential side effects (Eshkiki et al., 2024).

6. Application

6.1. As nutraceuticals

For encapsulating bioactive components of natural carriers and fortification of food products, nanostructured lipid carriers (NLCs) can be successfully applied to beverages with water-hydrophobic nutraceuticals. Food-derived extracellular vesicles (FDEVs) are naturally occurring non-replicating particles released by cells, with milk and plants serving as primary sources. FDEVs encapsulate natural active ingredients—such as polyphenols and flavonoids—protecting them from digestive damage and thus enhancing their absorption and utilisation within the body. For example, Jiang, Wang, et al. (2024) found that encapsulating curcumin in milk-derived FDEVs significantly boosted its stability and anti-tumuor properties. FDEVs transported bioactive molecules that conferred specific health benefits, including antioxidant, anti-inflammatory, and anti-cancer properties, thereby facilitating the development of functional foods tailored to specific health needs. FDEVs also served as carriers for oral drugs, improving their stability and bioavailability while diminishing their toxicity and immunogenicity. Subsequently, the use of milk-derived FDEVs for delivering paclitaxel markedly enhanced its anti-tumuor efficacy.

6.2. As food packaging materials

As food packaging materials, natural carriers have shown significant advantages in improving food safety and promoting sustainable development by virtue of their biocompatibility, degradability and multifunctionality. These materials also demonstrate excellent mechanical properties, providing a foundation for developing new composite films. For instance, combining polyphenol-rich tomato leaf extracts with food-grade polysaccharides could produce functional packaging films with high tensile strength. Such films could withstand compression and friction during logistics transportation, ensuring package integrity. Their superior mechanical properties also enhanced barrier performance, effectively inhibiting oxygen and moisture permeation. This significantly delayed food lipid oxidation and microbial spoilage processes (Hlaing et al., 2025). Furthermore, the controllable permeation-release properties of these systems offered innovative approaches for preserving perishable foods. Nanoparticles formed by hydrogen bonding and hydrophobic interactions between casein and epigallocatechin gallate could be uniformly dispersed in carrageenan/gelatin matrices, creating a controlled-release network (Li, Yang, et al., 2025). This mechanism effectively prevented initial rapid depletion of active ingredients while aligning with food spoilage progression, enabling sustained release of antimicrobial and antioxidant compounds.

Tan et al. (2024) developed a novel bio-polymer-based active packaging film (SC/CA-CIN) using sodium alginate (SA) and carboxymethyl cellulose (CMC) as matrices, incorporating cinnamaldehyde-loaded calcium nanoparticles (CA-CIN). CA-CIN enhanced the film's water vapour barrier properties, significantly reducing moisture evaporation and improving freshness retention. Under acidic conditions (pH 5.4) or high humidity, these nanoparticles underwent responsive decomposition to release cinnamaldehyde, effectively inhibiting the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Additionally, Eze et al. (2022) created a smart pH-sensing film (CHI-RPE films) based on a chitosan (CHI) matrix reinforced with broken riceberry phenolic extract (RPE). The anthocyanins in RPE undergo structural changes with pH variations, causing colour shifts in the film. Volatile alkaline nitrogen released during shrimp spoilage gradually transforms the film from orange-red to yellow. This visual colour change enabled real-time freshness monitoring of shrimp.

6.3. As biomedical products

Alginate, as a natural polysaccharide, exhibits considerable potential in pharmaceutical applications due to its unique biocompatibility, biodegradability, and gel-forming properties. A notable application involved the use of alginate-based hydrogel microcapsules as a shell for intestinal delivery of metformin (Kim et al., 2025). These microcapsules not only effectively protected the drug to ensure targeted delivery, but also modulated the intestinal microenvironment. This innovation presented a promising drug delivery system for the management of IBD. Besides, Meng et al. (2022) constructed folic acid (FA) modified pH/reducing dual-responsive carboxymethyl cellulose (CMC) using multi-step reaction-based microcapsules (FA-PRCMCs@CUR) for targeted delivery of the hydrophobic drug curcumin (CUR). The microcapsule had good biocompatibility, targeting and stimulus responsiveness, enabling drug release upon pH and reductive dual stimulation in tumuor cells, reducing damage to normal tissue.

7. Conclusions

The development of natural active carriers is crucial for their large-scale applications. The food-derived natural carriers have transformative potential in advancing precision nutrition for intestinal health. Firstly, diverse natural carriers can enable targeted delivery to the intestine. Food-derived microalgae, plant polysaccharides, and microbial vesicles overcome gastrointestinal barriers. Their unique size-tunable porosity, surface functionalization, and biocompatibility allow site-specific release in the colon while resisting degradation by gastric acid. Secondly, advanced construction strategies enhance the bioavailability of food-derived delivery systems. Critical techniques like ionic crosslinking, metal-phenolic coordination, and freeze drying-rehydration optimise drug loading and stimuli responsiveness. These methods confer dual-targeting capability and prolonged retention, significantly improving bioavailability of bioactive substances. Thirdly, natural carriers also play a synergistic biological role, such as anti-inflammatory, antioxidant effects, microbiota regulation and barrier repair. While food-derived systems demonstrate enhanced safety and multifunctionality, challenges including scalability limitations, gaps in long-term toxicity data, and industry standardization issues remain unresolved. Future research should focus on elucidating carrier-drug interaction mechanisms, conducting long-term safety evaluations, and establishing clinical translation pathways to facilitate the widespread adoption of precision nutrition in gut health management. Besides, through the intersection of multiple disciplines (materials science, nutrition and pharmacy), new strategies for precise intervention of intestinal diseases should be provided.

CRediT authorship contribution statement

Binyan Li: Writing – original draft, Visualization, Investigation, Formal analysis. Xin Feng: Supervision, Conceptualization. Shuhan Xu: Validation. Wentao Su: Resources, Project administration. Haoyingye Yao: Writing – review & editing. Xingyu Yuan: Writing – review & editing. Yuxiao Wang: Writing – review & editing, Funding acquisition.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

No data was used for the research described in the article.