Abstract
Inulin is a versatile biopolymer that is non-digestible in the upper alimentary tract and acts as a bifidogenic prebiotic which selectively promotes gut health and modulates gut–organ axes through short-chain fatty acids and possibly yet-to-be-known interactions. Inulin usage as a fiber ingredient in food has been approved by the FDA since June 2018 and it is predicted that the universal inulin market demand will skyrocket in the near future because of its novel applications in health and diseases. This comprehensive review outlines the known applications of inulin in various disciplines ranging from medicine to industry, covering its benefits in gut health and diseases, metabolism, drug delivery, therapeutic pharmacology, nutrition, and the prebiotics industry. Furthermore, this review acknowledges the attention of researchers to knowledge gaps regarding the usages of inulin as a key modulator in the gut–organ axes.
1. Introduction
Valentin Rose the Younger, a German pharmacologist, isolated inulin, a fructan, from the roots of Inula helenium in 1804, and Thomson coined the term inulin in 1917 (for a review see [1]. Inulin is the second most abundant carbohydrate storage in plants and is distributed across various parts such as bulbs, roots, root tubers, leaf bases, grains, and fruits. Dicotyledonous plants such as the Asteraceae and Campanulaceae families are rich sources of inulin. Nutritional inulin-containing plants include leek, onion, garlic, asparagus, Jerusalem artichoke, dahlia, chicory, yacon, etc. (Figure 1; [2]). Therefore, inulins with various origins are found in nature, and inulin and its inulin-laden products have been used in different applications, mainly in the food and drug industries, in all countries for more than two centuries.
Inulin is not enzymatically assimilated in the upper alimentary tract; therefore, it does not alter blood glucose levels nor interfere with the insulin–glucagon counter-balance [3]. Basically, inulin is a prebiotic, which is a non-digestible ingredient resistant to gastric acidity and enzymatic digestion. At the same time, inulin can be fermented by the colonic microbiota and can stimulate the growth and activity of some colonic beneficial bacteria necessary for health and well-being. The inulin-type fructans (inulin and fructooligosaccharides (FOS)) have prebiotic effects. Because inulin has β (2→1) linkages, it reaches the colon intact, without enzymatic hydrolysis in the upper gastrointestinal tract. It is hydrolyzed by β-fructosidase-producing bacteria and increases the Bifidobacteria population (bifidogenic effect) in the colon [4]. Therefore, the demand for inulin-based products will skyrocket in the next decade mainly because of their usage as prebiotics in health and diseases (www.transparencymarketresearch.com; accessed on 20 December 2024; [5]).
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Inulin as a Biopolymer; Chemical Structure, Anticancer Effects, Nutraceutical Potential and Industrial Applications: A Comprehensive Review
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Nutraceutical Potentials of Inulin
Several studies have evaluated the antioxidative activity of inulin (for a review see [71]). In this regard, one study showed that dietary supplementation with inulin improved the feed consumption and egg production rate of laying hens and increased the antioxidative activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and serum total antioxidant capacity and reduced levels of malondialdehyde, an index of lipid peroxidation [72]. It has been reported that dietary supplementation of inulin increased Bifidobacteria and Lactobacilli counts in the ceca of laying hens. Bifidobacterium spp. are lactic acid-producing bacteria that have SOD and lactic acid, both of which help scavenge free radicals. Another study indicated that pre-treatment with inulin prevents impairment of the colonic smooth muscle cell contractility induced by lipopolysaccharide exposure by a decrease in mucosal production of free radicals [73]. Another study focused on the antioxidative activity of inulin-based prebiotics, which promotes the development of functional fermented goat milk, indicated that the radical scavenging rate reached 75.52% and the scavenging rate of superoxide radicals was 21.09%. The researchers pointed out that inulin improved the nutritional value of functional foods [74]. In a similar vein, an impressive and seminal study reported on the consumption of a combination of the probiotic bacteria Lactobacillus casei (4 × 108 colony-forming unit (CFU)) and prebiotic inulin (400 mg) and suggested that dietary supplementation with this symbiotic may prevent oxidative stress in the plasma of healthy volunteers by increasing the ferric reducing ability of plasma (FRAP) and CAT activity [75]. In another study, the antioxidant activity of carboxymethyl inulin (CMI) was enhanced by chemical modification. The results revealed a significant enhancement in antioxidant activity upon the introduction of cationic Schiff bases into CMI as compared to the commercially available antioxidant Vc [76]. Therefore, the direct and indirect antioxidative effects of inulin that are mediated through the improvement of gut microbiota place inulin in a superior position to combat oxidative stress in both health and disease.
The regular intake of dietary fiber boosts the gut microbiome and health of the host in several ways. Dietary fibers (DFs) are indigestible products that have become a vital ingredient to be included in every healthy diet. DF is defined as carbohydrate polymers containing ≥ 10 monomeric units that resist digestion by endogenous enzymes in the small intestine. DF includes edible carbohydrate polymers, and synthesized carbohydrate polymers [65]. DF can be divided into “soluble DF” (SDF) and “insoluble DF” (IDF) according to solubility, and it can be further categorized into “partially fermentable fiber” and “completely fermentable fiber” based on its fermentability [65]. The health benefits of DF for hosts are revealed mainly by changes in gut microbiota composition and microbial metabolites. In this context, the role of inulin as a prebiotic DF is at the heart of the biopharmaceutical applications of this biopolymer, which may be due to its ability to modulate gut microbiota, enhance gut health and gut–organ axes (e.g., gut–kidney axis; Figure 6), and improve metabolic processes (for a review see [5,6,7,8,9,10,11,12,13,14,15]).
Prebiotics can be described as “selectively fermented ingredients that alter the configuration and activity in the gastrointestinal microbiota that confer positive effect”. In a seminal review [77], the beneficial impact of the dietary inclusion of inulin in human and animal models was discussed. The authors concluded that inulin as a fructan prebiotic can be a part of functional food products that promote health benefits to consumers. The review also vindicates the efficacy of inulin as a stabilizer, fat replacer, component in nanoformulations, and humectant in the cosmetic industry. Interestingly, hydrophobically modified inulin (HMI) has applications like the targeted release of drugs. In essence, it is important to explore the properties of SCFA inulin esters because they are less studied. Furthermore, HMI stabilizes various dispersion formulations as an excipient for producing hydrophobic drugs because inulin is generally recognized as safe (Figure 7; [78]). Therefore, inulin and inulin-based products may have health-promoting activities such as acting as DF, prebiotics, and drug carriers in the gut.
The prebiotic impact of inulin on the management of gastrointestinal disorder has been the subject of many studies (for a review see [79]). These researchers reviewed the positive impact of prebiotics in experimental colitis and human inflammatory bowel disease (IBD), and concluded that inulin has trophic effects on gut microflora via the enhancement of colonic production of short-chain fatty acids (SCFAs) and the subsequent growth of indigenous lactobacilli and bifidobacteria, decreasing mucosal lesion and mucosal inflammation by promoting host defense against invasion and pathogen translocation, and inhibiting gastrointestinal diseases like IBD. The therapeutic effects of prebiotic inulin-type fructans in severe bowel diseases like active and inactive Crohn’s disease need more deep investigations [80]. In another review [19], the history of inulin as a prebiotic and its ability to enhance the growth and functionality of Bifidobacterium bacteria, as well as its effect on host gene expression and metabolism, were discussed.
Finally, the authors proposed symbiotic (inulin plus probiotics) applications in the management of a group of diseases including cardiometabolic diseases after a deep discussion about various controversies regarding the effects of inulin on the health and diseases of the gut. In this continuum, the symbiotic formulations of inulin and other probiotics were reviewed Moreover, a bibliographic review focused on human clinical studies highlighted the main effects of inulin on human metabolic health, with a special focus on the mechanisms of action of this prebiotic. The authors concluded that inulin supplementation contributes to anthropometric indices control and improves metabolic status mainly through the selective favoring of SCFA-producer species from the genera Bifidobacterium and Anaerostipes [66]. In a seminal review [82], the role of inulin in the establishment of the gut microbial community during the first 1000 days of a child’s life was discussed, and the impact of inulin on the prevention of enteric diseases in adulthood was highlighted, in addition to the role of fructans in metabolic programming. In this context, another review [83] pertained to the microbial-derived products, including SCFAs, lipopolysaccharides and secondary bile acids, that may be involved in the regulation of hepatic lipid metabolism. Finally, they concluded that the relationships between bacterial species (e.g., competition and mutualism), play key roles in the degradation of inulin and the regulation of the microbial structure.
Regarding the therapeutic effects of inulin-type fructans (ITFs) and prebiotics on IBDs and Crohn’s disease, the findings of different studies are controversial, possibly due to the altering microbial community (for a review see [84,85]. In a systematic review [86], all aspects of inulin-type fructans including short-chain fructooligosaccharides (scFOS), oligofructose, and inulin were deeply discussed and the authors proposed the personalization of prebiotic applications in precise and personalized medicine. To personalize the ITFs, we must focus on the plasticity of the microbial community of the intestine, postbiotics produced during microbial modulation, and their effects on extra-intestinal tissues (for a review, see [87,88]. In addition to the DF formulation of inulin, innovative synthetic or semi-synthetic inulin-based delivery systems, such as hydrogels and nanoparticles, are designed for their sustained and controlled-release formulations. The mechanisms and bacterial enzymes involved in inulin degradation by gut microbiota have been reviewed [89]. An inulin-rich flour has been formulated from Smallanthus sonchifolius, popularly known as yacon, which is a member of the Asteraceae family (for a review see [64]. The authors showed that the intake of yacon flour can reduce glycemia, HbA1c, advanced glycation ends, plasma lipids, body fat mass, body weight, and waist circumference and improve intestinal microbiota and antioxidant status. In conclusion, inulin has many applications in the nutraceutical sector, especially for innovating new functional formulations in feed/food technologies; however, further studies are welcomed to assess its effects on gut–organ axes.
Karimi, I.; Ghowsi, M.; Mohammed, L.J.; Haidari, Z.; Nazari, K.; Schiöth, H.B. Inulin as a Biopolymer; Chemical Structure, Anticancer Effects, Nutraceutical Potential and Industrial Applications: A Comprehensive Review. Polymers 2025, 17, 412. https://doi.org/10.3390/polym17030412
