Composition for promoting intestinal development and application thereof

Abstract

The present invention relates to a composition for promoting intestinal development and its use. The composition comprises lactose-N-neotetraose and 3'-sialyllactose. The composition for promoting intestinal development according to the present invention can upregulate the transcription levels of intestinal glycocalyx development-related genes HAS1, HAS2, and HAS3, as well as the transcription level of EXT2, thereby synergistically promoting intestinal glycocalyx development.

Description

Technical Field

[0001] The present invention relates to the technical field of compositions containing human milk oligosaccharides, and in particular to a composition for promoting intestinal development and applications thereof. Background Art

[0002] The intestinal barrier is considered the gatekeeper of human health. While responsible for the passage and absorption of nutrients, it also prevents pathogens from entering the body. Furthermore, it regulates crosstalk between the intestinal luminal microbiota and macromolecules, maintaining tolerance and immune responses. After birth, this gatekeeping function of the intestinal barrier is not fully developed. Any disruption of the intestinal barrier function in neonates can have long-term consequences and may play a role in the development of gastrointestinal infections and inflammatory bowel disease (IBD). Furthermore, it influences the development of other diseases in childhood and adulthood, such as obesity and allergies.

[0003] Breast milk is the gold standard for infant nutrition, with human milk oligosaccharides (HMOs) being the primary component that distinguishes it from other mammalian milks. In infant formula, HMOs have the important function of stimulating microbial colonization of the gastrointestinal tract and promoting the development of intestinal barrier function. One possible way to achieve this is by stimulating the development of the epithelial glycocalyx on intestinal epithelial cells. The glycocalyx on neonatal intestinal epithelial cells provides binding sites for commensal microorganisms, and a well-developed glycocalyx prevents the adhesion of pathogens and acts as a barrier to luminal toxins and enzymes.

[0004] Currently, clinical intervention studies examining the direct regulatory effects of HMOs on intestinal cells and structure are limited. However, preclinical data suggest that HMOs have a positive impact on intestinal maturation. Intestinal cell lines such as Caco-2 are often used in vitro to investigate the mechanisms by which nutrients and microbial metabolites influence epithelial integrity. Studies have demonstrated that N-lactosylneotetraose (LNnT), 2'-fucosyllactose (2'-FL), and 3'-sialyllactose (3'-SL) can promote tight junction protein expression and increase cell differentiation along the crypt-villus axis. 2'-fucosyllactose and 3'-fucosyllactose also have positive effects on mucin glycoprotein expression. In vivo animal studies have shown that supplementation with 2'-FL significantly increases epithelial integrity and reduces the incidence of colitis. However, limited research has examined the effects of HMOs on the glycocalyx, particularly regarding their effects on glycocalyx function. Summary of the Invention

[0005] Technical issues

[0006] Therefore, the first object of the present invention is to provide an application of 3'-sialyllactose (3'-SL) and lacto-N-neotetraose (LNnT) in synergistically promoting glycocalyx development.

[0007] The second object of the present invention is to provide an application of a specific ratio of 3'-sialyllactose (3'-SL) and lacto-N-neotetraose (LNnT) in synergistically promoting glycocalyx development.

[0008] The third object of the present invention is to provide an application of a specific ratio of 3'-sialyllactose (3'-SL) and lacto-N-neotetraose (LNnT) to synergistically promote the transcription level of glycocalyx development-related genes, thereby promoting intestinal glycocalyx development.

[0009] Technical Solution

[0010] This application explored the effects of LNnT and 3'-SL on the development and function of Caco-2 glycocalyx in intestinal epithelial cells at the cellular level, laying a theoretical foundation for the application of LNnT and 3'-SL.

[0011] According to one aspect of the present invention, a composition is provided, comprising lacto-N-neotetraose and 3'-sialyllactose.

[0012] In one embodiment, the ratio of lactose-N-neotetraose to 3'-sialyllactose is 1:1 to 3:1 by weight, preferably 1:1, 1:2, 2:1 and 3:1 by weight, more preferably 1:1 or 3:1 by weight, most preferably 3:1 by weight.

[0013] In one embodiment, in the composition, the concentration of lactose-N-neotetraose is 0.17-0.35 mg / mL, and the concentration of 3'-sialyllactose is 0.05-0.3 mg / mL.

[0014] Preferably, in the composition, the concentration of lactose-N-neotetraose is 0.2-0.3 mg / mL, preferably 0.2-0.27 mg / mL; the concentration of 3'-sialyllactose is 0.06-0.2 mg / mL, preferably 0.08-0.18 mg / mL.

[0015] In a specific embodiment of the present invention, when the above ratio of lacto-N-neotetraose to 3'-sialyllactose is satisfied, the concentrations of lacto-N-neotetraose and 3'-sialyllactose can be any value within the above concentration range.

[0016] In another aspect, the present invention provides use of the composition described above in preparing food or health care products.

[0017] In another aspect, the present invention provides use of the composition in preparing a product for promoting intestinal glycocalyx development.

[0018] In one embodiment, the composition is used to upregulate the transcription level of genes related to intestinal glycocalyx development, thereby promoting intestinal glycocalyx development.

[0019] In a specific embodiment, the composition is used to upregulate the transcription levels of has1, has2, and has3, promote the synthesis of hyaluronic acid synthase in the glycocalyx layer, and thus promote the secretion of hyaluronic acid in the glycocalyx layer.

[0020] Preferably, the composition is used to upregulate the transcription level of has2, promote the synthesis of hyaluronic acid synthase in the glycocalyx layer, and thus promote the secretion of hyaluronic acid in the glycocalyx layer.

[0021] In another specific embodiment, the composition is used to upregulate the transcription level of ext2, thereby promoting the synthesis of heparan sulfate in the glycocalyx layer.

[0022] Beneficial effects

[0023] The composition provided by the present invention, comprising lactose-N-neotetraose and 3'-sialyllactose, when combined in a specific ratio, can synergistically upregulate the transcription levels of glycocalyx development-related genes HAS1, HAS2, and HAS3, as well as the transcription level of EXT2, thereby synergistically promoting intestinal glycocalyx development. In particular, it significantly upregulates the transcription levels of HAS2 and EXT2, thereby synergistically promoting intestinal glycocalyx development. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Shown is the effect of LNnT on the transcription level of gpc1 in Caco-2 cells. Figure 2 Shown is the effect of 3'-SL on gpc1 transcription levels in Caco-2 cells;

[0025] Figure 3 、 Figure 4 、 Figure 5 The effects of LNnT on the transcriptional levels of has1, has2 and has3 in Caco-2 cells are shown respectively. Figure 6 、 Figure 7 、 Figure 8 The effects of 3'-SL on the transcription levels of has1, has2, and has3 in Caco-2 cells are shown respectively;

[0026] Figure 9 and Figure 10 The effects of LNnT on the transcriptional levels of ext1 and ext2 in Caco-2 cells are shown respectively. Figure 11 and Figure 12 The effects of 3′-SL on the transcription levels of ext1 and ext2 in Caco-2 cells are shown, respectively;

[0027] Figure 13Shown are the effects of LNnT and 3'-SL on gpc1 transcription levels in Caco-2 cells;

[0028] Figure 14 、 Figure 15 、 Figure 16 Shown are the effects of the combination of LNnT and 3'-SL on the transcriptional levels of has1, has2, and has3 in Caco-2 cells, respectively;

[0029] Figure 17 、 Figure 18 Shown are the effects of the combination of LNnT and 3'-SL on the transcriptional levels of ext1 and ext2 in Caco-2 cells, respectively. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be described in detail below with reference to specific embodiments. The described embodiments are only part of the embodiments of the present invention, but not all of them.

[0031] Human milk oligosaccharides (HMOs) are diverse, mainly including neutral HMOs and acidic HMOs. Neutral HMOs include 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), N-lactotetraose (LNT) and lacto-N-neotetraose (LNnT); acidic HMOs include 3'-sialyllactose (3'-SL), 6'-sialyllactose (6'-SL) and sialyllactose-N-tetraose (LST).

[0032] The glycocalyx is composed of glycans and proteins. Proteoglycans are generally considered the most important component of the glycocalyx and form its backbone. Furthermore, the glycocalyx contains glycosaminoglycan chains linked to the proteoglycan core protein. Heparan sulfate (HS) and hyaluronic acid (HA) are the major glycosaminoglycan components of the glycocalyx.

[0033] Transcript levels of genes involved in glycocalyx development in Caco-2 cells were measured, including glypican 1 (gpc1), hyaluronan synthase 1 (has1, has2, has3), and exosome glycosyltransferase 1 (ext1, ext2). gpc1 encodes glypican 1 (GPC1), a protein backbone of the glycocalyx layer and a key carrier of glycosaminoglycan chains, including hyaluronan (HA) and heparan sulfate (HS). has1, has2, and has3 encode hyaluronan synthase (HAS), which is essential for the synthesis of HA, a highly viscous component of the intestinal mucus layer responsible for tissue repair, stability, and anti-inflammatory effects. Compared to HAS1 and HAS2, HAS3 synthesizes low-molecular-weight HA, which is essential for intestinal stem cell development. Furthermore, ext1 and ext2 are involved in the elongation of heparan sulfate (HS) chains and are responsible for integrating HS chains with nucleotide sugars in the Golgi apparatus. HS synthesis supports organogenesis, growth factor signaling, and bacterial adhesion.

[0034] Unless otherwise specified, the raw materials and equipment used in the present invention are commonly used raw materials and equipment in this field, and the methods used in the present invention are conventional methods in this field.

[0035] Unless otherwise indicated, parts are parts by weight, % are wt%, and temperatures are in degrees Celsius. In the following examples, the following materials and methods were used.

[0036] Example

[0037] Example 1: Caco-2 cell culture

[0038] Human colon adenocarcinoma cells Caco-2 were cultured in MEM complete medium (purchased from Nanjing Senbeijia Biotechnology Co., Ltd.) containing 20% ​​high-quality fetal bovine serum and grown at 25 cm 2 Culture cells in a flask in a CO2 incubator at 37°C, 5% CO2, and 95% relative humidity. Change the culture medium every other day or two. When cells reach 80% to 90% confluence, digest them with 0.25% trypsin and subculture at a 1:3 ratio.

[0039] Example 2: Effects of LNnT and 3'-SL on the Development of the Glycocalyx Layer in Caco-2 Cells

[0040] Adjust the Caco-2 cell density to 1 × 10 5 pieces / cm 2Cells were seeded in 24-well plates and the corresponding intervention substances, namely, LNnT and 3'-SL (both purchased from Suzhou Yixi Biotechnology Co., Ltd.) at specific ratios, were added to MEM complete medium according to group and incubated for 36 hours. MEM medium was used as a blank control and incubated for 36 hours (see Table 2 below).

[0041] After the incubation, total cell RNA was extracted and reverse transcribed, and the transcription levels of glycocalyx development-related genes glypican 1 (gpc1), hyaluronan synthase 1 (has1, has2, has3), and exosome glycosyltransferase 1 (ext1, ext2) in Caco-2 cells were measured by qPCR (Nanjing Novozymes Biotechnology Co., Ltd.).

[0042] Table 1 qPCR primer sequences

[0043]

[0044] Table 2 Combinations of LNnT and 3'-SL at specific ratios and co-incubation methods of LNnT and 3'-SL alone

[0045]

[0046] Examples 2-1 to 2-6 respectively verified the effects of different concentrations of LNnT alone and 3'-SL alone on the development of the glycocalyx layer of Caco-2 cells.

[0047] The specific steps are as follows:

[0048] Adjust the Caco-2 cell density to 1 × 10 5 pieces / cm 2 , seeded in 24-well plates, and specific concentrations of LNnT and 3'-SL were added to the MEM complete medium according to the group, and incubated for 36 hours. The final concentrations of 3'-SL in the MEM complete medium were 0.05 mg / mL, 0.1 mg / mL, 0.2 mg / mL and 0.4 mg / mL, respectively. The final concentrations of LNnT in the MEM complete medium were 0.05 mg / mL, 0.3 mg / mL and 0.6 mg / mL, respectively. After the incubation, total cell RNA was extracted and reverse transcribed, and the transcription levels of glycocalyx development-related genes phosphatidylinositol protein glycan 1 (gpc1), hyaluronic acid synthase 1 (has1, has2, has3), and exosome glycosyltransferase 1 (ext1, ext2) in Caco-2 cells were measured by qPCR. The results are shown in the figure. Figures 1 to 12 .

[0049] Example 2-1 Effect of LNnT alone on the protein skeleton development of the glycocalyx layer

[0050] Figure 1 Shown is the effect of LNnT on the transcription level of gpc1 in Caco-2 cells.

[0051] Depend on Figure 1 It can be seen that only 0.05 mg / mL of LNnT can upregulate the transcription level of gpc1, but the difference is not significant compared with the control group. This shows that LNnT has a certain promoting effect on the protein skeleton development of the glycocalyx layer, but the effect is not obvious.

[0052] Example 2-2 Effect of 3'-SL alone on the protein skeleton development of the glycocalyx layer

[0053] Figure 2 Shown is the effect of 3'-SL on the transcription level of gpc1 in Caco-2 cells.

[0054] Depend on Figure 2 The results showed that all four intervention concentrations of 3'-SL upregulated the transcriptional level of gpc1, with 0.05 mg / mL, 0.1 mg / mL, and 0.2 mg / mL of 3'-SL significantly upregulating the transcriptional level of gpc1 (p < 0.01, p < 0.001). This suggests that 0.05 mg / mL, 0.1 mg / mL, and 0.2 mg / mL of 3'-SL promote the development of the protein skeleton of the glycocalyx layer.

[0055] Example 2-3 Effect of LNnT alone on glycocalyx hyaluronan synthase

[0056] Figure 3 、 Figure 4 、 Figure 5 The effects of LNnT on the transcriptional levels of has1, has2, and has3 in Caco-2 cells are shown respectively.

[0057] Depend on Figure 3 、 Figure 4 、 Figure 5 It can be seen that LNnT can upregulate the transcription levels of has1, has2, and has3, but the difference is not significant compared with the control group. This shows that only 0.05 mg / mL of LNnT has a certain promoting effect on hyaluronic acid secretion in the glycocalyx layer, but the difference is not significant compared with the control group.

[0058] Example 2-4 Effect of 3'-SL alone on glycocalyx hyaluronan synthase

[0059] Figure 6 、 Figure 7 、 Figure 8 The effects of 3'-SL on the transcriptional levels of has1, has2 and has3 in Caco-2 cells are shown respectively.

[0060] like Figure 6 、 Figure 7 、 Figure 8 As shown, all four intervention concentrations of 3'-SL upregulated the transcriptional levels of has1, has2, and has3. 0.05 mg / mL and 0.1 mg / mL of 3'-SL significantly upregulated the transcriptional level of has1 (p < 0.01), 0.1 mg / mL of 3'-SL significantly upregulated the transcriptional level of has2 (p < 0.01), and 0.05 mg / mL and 0.1 mg / mL of 3'-SL significantly upregulated the transcriptional level of has3 (p < 0.005, p < 0.001, respectively). This indicates that low concentrations of 3'-SL have a certain promoting effect on hyaluronic acid secretion in the glycocalyx layer. (Note: The significant difference here is significant compared with the control group. The absence of significance indicates that the difference is not significant. Even if some differences appear to be significant, it may be due to large errors, resulting in insignificant differences.)

[0061] Example 2-5 Effect of LNnT alone on heparan sulfate in the glycocalyx layer

[0062] Figure 9 and Figure 10 Shown are the effects of LNnT on the transcriptional levels of ext1 and ext2 in Caco-2 cells, respectively.

[0063] like Figure 9 and Figure 10 As shown, only 0.05 mg / mL of LNnT upregulated ext1 transcription, but the effect was not significant (p>0.05). The three intervention concentrations of LNnT had no effect on ext2 transcription, indicating that LNnT alone has a very weak effect on promoting heparan sulfate synthesis in the glycocalyx.

[0064] Example 2-6 Effect of 3'-SL alone on heparan sulfate in the glycocalyx layer

[0065] Figure 11 and Figure 12 Shown are the effects of 3'-SL on the transcription levels of ext1 and ext2 in Caco-2 cells, respectively.

[0066] like Figure 11 and Figure 12As shown, of the four selected intervention concentrations of 3'-SL, except for 0.4 mg / mL, which had no effect on ext1 transcription, the remaining concentrations all upregulated the transcription levels of ext1 and ext2. However, only 0.1 mg / mL of 3'-SL significantly upregulated the transcription level of ext1 (p < 0.01), while 0.05 mg / mL, 0.1 mg / mL, and 0.2 mg / mL of 3'-SL all significantly upregulated the transcription level of ext2 (p < 0.05, p < 0.01). This suggests that 3'-SL has a certain promoting effect on heparan sulfate synthesis in the glycocalyx layer.

[0067] Example 3 Effect of the Combination of LNnT and 3'-SL on the Development of the Glycocalyx Layer in Caco-2 Cells

[0068] Examples 3-1 to 3-3 respectively verified the effects of a combination of LNnT and 3'-SL in a specific ratio on the development of the glycocalyx layer of Caco-2 cells.

[0069] The specific steps are as follows:

[0070] Adjust the Caco-2 cell density to 1 × 10 5 pieces / cm 2 Cells were seeded in 24-well plates and incubated for 36 h using MEM complete medium as a blank control. A combination of LNnT and 3'-SL at a specific ratio, as well as LNnT and 3'-SL alone, was added to the plates according to the grouping.

[0071] The ratios of LNnT to 3'-SL added and the final concentrations in MEM complete medium were 1:1 (0.175 mg / mL LNnT + 0.175 mg / mL 3'-SL), 2:1 (0.235 mg / mL LNnT + 0.115 mg / mL 3'-SL), 1:2 (0.115 mg / mL LNnT + 0.235 mg / mL 3'-SL), and 3:1 (0.263 mg / mL LNnT + 0.088 mg / mL 3'-SL). The final concentration of LNnT or 3'-SL alone in MEM complete medium was 0.35 mg / mL. After incubation for 36 hours, total RNA was extracted from the cells and reverse transcribed. The transcription levels of glycocalyx development-related genes such as glypican 1 (gpc1), hyaluronan synthase 1 (has1, has2, has3), and exosome glycosyltransferase 1 (ext1, ext2) in Caco-2 cells were measured by qPCR. Figures 13 to 18 .

[0072] Example 3-1 Effect of the Combination of LNnT and 3'-SL on the Protein Skeleton of the Glycocalyx Layer

[0073] Figure 13 Shown are the effects of LNnT and 3'-SL on the transcription level of gpc1 in Caco-2 cells.

[0074] Depend on Figure 13 It can be seen that the selected LNnT and 3'-SL ratio combinations and 0.35 mg / mL LNnT and 3'-SL had no significant effect on the gpc1 transcription level, indicating that the LNnT and 3'-SL combination and high concentrations of LNnT and 3'-SL had no significant promoting effect on the development of the glycocalyx protein skeleton (Note: the significance here is the difference between groups).

[0075] Example 3-2 Effect of the Combination of LNnT and 3'-SL on Glycocalyx Hyaluronic Acid Synthase

[0076] Figure 14 、 Figure 15 、 Figure 16 Shown are the effects of the combination of LNnT and 3'-SL on the transcriptional levels of has1, has2, and has3 in Caco-2 cells, respectively.

[0077] Depend on Figure 14 It can be seen that the selected LNnT and 3'-SL ratios of 1:1 and 3:1 significantly upregulated the transcription level of has1, and the upregulation effect on the transcription level of has1 was significantly higher than that of using 0.35 mg / mL LNnT and 3'-SL alone.

[0078] Depend on Figure 15 It can be seen that the selected LNnT and 3'-SL ratios of 2:1 and 3:1 compositions significantly upregulated the transcription level of has2, and the composition with a ratio of 3:1 had a significantly higher upregulation effect on the has2 transcription level than using 0.35 mg / mL LNnT and 3'-SL alone.

[0079] Depend on Figure 16 It can be seen that the selected LNnT and 3'-SL ratios of 1:2 and 3:1 compositions significantly upregulated the transcription level of has3, and the 3:1 composition had a significantly higher upregulation effect on has3 transcription level than using 0.35 mg / mL LNnT alone.

[0080] In summary, the composition of LNnT and 3'-SL in a specific ratio has a significant promoting effect on the synthesis of hyaluronic acid in the glycocalyx layer. When the ratio of LNnT to 3'-SL is 3:1, the up-regulation effect on has1 and has2 is significantly higher than that of 0.35 mg / mL LNnT and 3'-SL, and the up-regulation effect on has3 is significantly higher than that of 0.35 mg / mL LNnT, indicating that when the ratio of LNnT to 3'-SL is 3:1, it has a significant synergistic promoting effect on the synthesis of hyaluronic acid in the glycocalyx layer.

[0081] Example 3-3 Effect of the Combination of LNnT and 3'-SL on Heparan Sulfate in the Glycocalyx Layer

[0082] Figure 17 、 Figure 18 Shown are the effects of the combination of LNnT and 3'-SL on the transcriptional levels of ext1 and ext2 in Caco-2 cells, respectively.

[0083] like Figure 17 As shown, the selected LNnT and 3'-SL ratio combinations and 0.35 mg / mL LNnT and 3'-SL had no significant effect on the ext1 transcription level, indicating that the LNnT and 3'-SL combination and high concentrations of LNnT and 3'-SL had no significant promoting effect on the development of the glycocalyx layer protein skeleton.

[0084] like Figure 18 As shown, the selected LNnT and 3'-SL ratio of 3:1 significantly upregulated the transcription level of ext2, and the upregulation effect of the 3:1 ratio composition on the transcription level of ext2 was significantly greater than that of 0.35 mg / mL LNnT alone. This indicates that the LNnT and 3'-SL ratio of 3:1 composition can promote the synthesis of heparan sulfate in the glycocalyx layer by synergistically promoting the transcription level of ext2.

[0085] The above experimental results show that only 0.05 mg / mL of LNnT upregulated the transcription levels of has1, has2, and has3, indicating that LNnT alone has a certain effect on promoting hyaluronic acid secretion in the glycocalyx layer, but the difference was not significant compared with the control group. Only 0.05 mg / mL of 3'-SL significantly upregulated the transcription levels of has1 and has3, indicating that low concentrations of 3'-SL have a certain effect on promoting hyaluronic acid secretion in the glycocalyx layer. However, after the present invention combines LNnT and 3'-SL in a certain ratio, the specific ratio of LNnT and 3'-SL composition has a significant promoting effect on the synthesis of hyaluronic acid in the glycocalyx layer. When the ratio of LNnT and 3'-SL is 3:1, the up-regulation effect on has1 and has2 is significantly higher than that of 0.35 mg / mL LNnT and 3'-SL, and the up-regulation effect on has3 is significantly higher than that of 0.35 mg / mL LNnT, indicating that when the ratio of LNnT and 3'-SL is 3:1, it has a significant synergistic promoting effect on the synthesis of hyaluronic acid in the glycocalyx layer.

[0086] The three selected intervention concentrations of LNnT (used alone) had no significant effect on the transcription levels of ext1 and ext2 (p>0.05), indicating that LNnT alone has a weak effect on promoting heparan sulfate synthesis in the glycocalyx. The three selected intervention concentrations of 3'-SL (used alone) all increased the transcription levels of ext1 and ext2, except for 0.4 mg / mL, which had no effect on ext1 transcription. However, the other concentrations did increase the transcription levels of ext1 and ext2, but the effect was not significant (p>0.05). This suggests that 3'-SL has a weak effect on promoting heparan sulfate synthesis in the glycocalyx. However, the present invention combined LNnT and 3'-SL in a specific ratio. The selected combination of LNnT and 3'-SL at a ratio of 3:1 significantly increased the transcription level of ext2, and the upregulation of ext2 transcription by this combination was significantly greater than that of 0.35 mg / mL LNnT alone. These results indicate that a combination of LNnT and 3'-SL at a ratio of 3:1 can promote the synthesis of heparan sulfate in the glycocalyx layer by synergistically promoting the transcription level of ext2.

[0087] In conclusion, the present invention can synergistically upregulate the transcription levels of has1, has2, has3, and ext2 by combining LNnT and 3'-SL in a certain ratio.

[0088] Adding 3'-SL to Caco-2 cells during non-adherent growth simulates the maturation phase of the intestine. Under these conditions, 3'-SL significantly promotes the development of the Caco-2 cell glycocalyx layer. Furthermore, the combination of LNnT and 3'-SL at specific ratios exhibits a significant synergistic effect on glycocalyx development. This suggests that supplementing a specific ratio of LNnT and 3'-SL during the maturation phase of the intestine can significantly promote the development of the intestinal glycocalyx layer, thereby promoting overall healthy intestinal development.

Claims

1. A composition, characterized in that The composition consists of lactose-N-neotetraose and 3'-sialyllactose, and the ratio of the lactose-N-neotetraose to the 3'-sialyllactose is 1:1 to 3:1 by weight.

2. The composition according to claim 1, wherein In the composition, the concentration of lactose-N-neotetraose is 0.17-0.35 mg / mL, and the concentration of 3'-sialyllactose is 0.05-0.3 mg / mL.

3. The composition according to claim 1, wherein In the composition, the concentration of lactose-N-neotetraose is 0.2-0.3 mg / mL, and the concentration of 3'-sialyllactose is 0.06-0.2 mg / mL.

4. Use of the composition according to any one of claims 1 to 3 in the preparation of food or health products.

5. Use of a composition in the preparation of a product for promoting intestinal glycocalyx development, characterized in that: The composition consists of lactose-N-neotetraose and 3'-sialyllactose, and the ratio of lactose-N-neotetraose to 3'-sialyllactose is 1:1 to 3:1 by weight.

6. The use according to claim 5, characterized in that The composition is used for up-regulating the transcription level of genes related to intestinal glycocalyx development, thereby promoting intestinal glycocalyx development.

7. The use according to claim 5 or 6, characterized in that The composition is used to upregulate has1, has2, has3 The transcription level of hyaluronan synthase in the glycocalyx layer is increased, thereby promoting the secretion of hyaluronan in the glycocalyx layer.

8. The use according to claim 7, characterized in that The composition is used to upregulate has2 The transcription level of hyaluronan synthase in the glycocalyx layer is increased, thereby promoting the secretion of hyaluronan in the glycocalyx layer.

9. The use according to claim 5 or 6, characterized in that: The composition is used to upregulate ext2 The transcriptional level of β-actin is increased, thereby promoting the synthesis of heparan sulfate in the glycocalyx layer.

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