Gastrodia elata Blume, a famous top-class traditional Chinese medicine, was first recorded in Shennong’s Classic of Materia Medica which explained the “Bu-Yi” (improving the deficiency of the body and maintaining health) role of G. elata (Su et al., 2023). The Compendium of Materia Medica recorded that G. elata was the number one Chinese medicine in terms of the “Bu-Yi” effect. Similarly, in modern clinical practice, G. elata is used to protect the brain, liver, and kidneys, thereby regulating human health (Gong et al., 2024). Traditionally, water decoction is a commonly used form of G. elata to promote the dissolution of its active components (Huang et al., 2021; Lin et al., 2018). In the aqueous solution of G. elata, polysaccharides accounted for the largest proportion and were one of the main medicinal components (Li, N. et al., 2023). G. elata polysaccharide (GEP) was mainly composed of glucose and also contained galactose, galacturonic acid, glucuronic acid, and α-1,4-glucan, α-1,4,6-glucan, α-1, 3, 4-glucan, β-1,6-glucan as the backbone (Chen et al., 2011; Huo et al., 2021; Zhu, H.D. et al., 2019). As a highly active polysaccharide, GEP has been reported to have immunomodulatory, neuroprotective, and anti-aging effects (Li, N. et al., 2023; Zhu, H.D. et al., 2019), and is one of the main medicinal ingredients in G. elata for maintaining health.

Oral administration is the most common form of traditional medicine. However, digestive enzymes, bile salts, and pH in saliva, gastric, and intestinal conditions may affect the physicochemical properties of polysaccharides, such as the monosaccharide composition, molecular weight, and chain conformation (Guo et al., 2021; Liang et al., 2020; Liu et al., 2020). The function of polysaccharides is closely related to the changes in structure during digestion. After digestion, small molecules of sugars are easily absorbed in the small intestine, but most polysaccharides except starch cannot be completely digested in the digestive medium (Liang et al., 2020). These indigestible polysaccharides pass through the upper digestive tract to the colon where they are fermented and utilized by the gut microbiota (Ji, H.H. et al., 2022; Li, H.L. et al., 2022; Li et al., 2020). In this process, the composition of the gut microbiota and the secretion of metabolites such as short-chain fatty acids (SCFAs) were regulated, thereby regulating human health (Ding et al., 2019; Liu et al., 2021; Xu et al., 2020). The structural changes of polysaccharides during digestion and the prebiotic effect of indigestible polysaccharides played an important role in explaining the bioactivities of polysaccharides. However, it was not clear how GEP changed during digestion and whether it could play a role in improving human health through the “gut” axis.

Therefore, in vitro salivary, gastric, and intestinal digestion experiments and human fecal fermentation experiments were used to explore GEP. The experiments mainly investigated the changes of reducing sugars, free monosaccharides, and physicochemical properties such as structural configuration, thermal stability, and morphological characteristics of GEP during digestion. Moreover, polysaccharide consumption, pH value changes, SCFAs production, and changes in gut microbiota during fermentation were also discussed. The results of this study aim to explain the effect mechanism of GEP from the perspective of the digestive characteristics and the “gut” axis.