Prebiotic Oligosaccharides in Skin Health: Benefits, Mechanisms, and Cosmetic Applications

Abstract

Prebiotic oligosaccharides have attracted significant interest in dermatology and skin health due to their ability to modulate the skin microbiome and microbiota-host interactions. This review offers a novel dual perspective, systematically examining the benefits of both oral intake and topical application of prebiotic oligosaccharides, including well-established prebiotics (e.g., human milk oligosaccharides, galacto- and fructo-oligosaccharides) and emerging prebiotic candidates (e.g., gluco-oligosaccharides, chitosan-oligosaccharides, agaro-oligosaccharides). First, cutting-edge synthetic processes for producing diverse oligosaccharides and their structural chemistry are introduced. Then, we discuss in vitro studies demonstrating their efficacy in promoting skin commensals, inhibiting pathogens, and conferring protective effects, such as antioxidant, anti-inflammatory, anti-melanogenic, and wound-healing properties. Furthermore, we emphasize in vivo animal studies and clinical trials revealing that prebiotic oligosaccharides, administered orally or topically, alleviate atopic dermatitis, enhance skin hydration, attenuate acne, and protect against photo-aging by modulating skin-gut microbiota and immune responses. Mechanistically, we integrate genetic and molecular insights to elucidate how oligosaccharides mediate these benefits, including gut-skin axis crosstalk, immune regulation, and microbial metabolite signaling. Finally, we highlight current commercial applications of oligosaccharides in cosmetic formulations while addressing scientific and practical challenges, such as structure-function relationships, clinical scalability, and regulatory considerations. This review bridges mechanistic understanding with practical applications, offering a comprehensive resource for advancing prebiotic oligosaccharides-based skincare therapies.

Keywords: commercial cosmetics; non-digestible oligosaccharides; pathogen inhibition; skin barrier function; skin diseases.

Figure 1

Illustration of prebiotic oligosaccharides through oral administration or topical application to confer health benefits to the skin and application in cosmetic formulations.

Figure 2

Industrial enzymatic production of human milk oligosaccharides. Biosynthetic pathway of (a) 3′-sialylactose/6′-sialylactose and (b) 2′-fucosyllactose from glucose and lactose (Lac). Sugar nucleotides, such as cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-NeuAc) and guanosine diphosphate fucose (GDP-Fuc), are biosynthesized internally from glucose, and glycosyltransferases transfer the sugar moiety of the nucleotide sugar to lactose. (Reproduced with permission from [31]). Notes: GlcNAc: N-acetylglucosamine; ManNAc: N-acetylmannosamine; NeuNAc: N-acetylneuraminic acid; Man-6P: mannose 6-phosphate; Man-1P: mannose 1-phosphate; GDP-Man: guanosine pyrophosphate mannose.

Figure 3

Illustration of the enzymatic production of galacto-oligosaccharides (GOSs) from lactose via hydrolysis and transgalactosylation reactions catalyzed by β-galactosidase (lactase). Note: DP—degree of polymerization.

Figure 4

Chemical structures of two commercial fructo-oligosaccharides (FOSs) from different production methods. (A) S-FOSs produced from the enzymatic transglycosylation of sucrose; (B) H-FOSs produced from the controlled enzymatic hydrolysis of inulin (G and F denote glucose and fructose units, respectively. (Reproduced with permission from [56].)

Figure 5

Mechanisms of pathogen colonization resistance mediated by the skin microbiota (reproduced with permission from [3]).

Figure 6

Human milk oligosaccharide 2′-fucosyllactose (2′-FL) promotes melanin degradation via the autophagic AMPK–ULK1 signaling axis. 2′-FL activates AMPK, which, in turn, phosphorylates ULK1 at Ser555 and inhibits Ser757-mediated inactivation, with consequent autophagy initiation (reproduced with permission from [89]).

Figure 7

General action mechanisms of prebiotics (oligosaccharides and polysaccharides) of antioxidant and anti-inflammatory effects (reproduced with permission from [104]). Notes: XOSs: xylo-oligosaccharides; MOSs: mannan oligosaccharides; ROS: reactive oxygen species; IL-10: interleukin-10; GLP-1: glucagon-like peptide-1.

Figure 8

Role of thiolated poly- and oligosaccharide-based (e.g., oligosaccharides from chitosan, hyaluronic acid) hydrogels for different stages of wound healing applications (reproduced with permission from [96]).

Figure 9

Metabolism of human milk oligosaccharide (HMO)-induced immunological effects and protection of skin from atopic dermatitis development (reproduced with permission from [17]). Notes: SCFAs: short-chain fatty acids; IL: interleukin; TGF-β: transforming growth factor-β; T-reg: regulatory T cells; TNF-α: tumor necrosis factor α; ROS: reactive oxygen species.

Figure 10

Possible mechanisms of human milk oligosaccharides (HMOs) in the prevention of allergic diseases (reproduced with permission from [122]). Notes: SCFAs: short-chain fatty acids; DCs: dendritic cells; TLRs: toll-like receptors.