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Objective: To evaluate the therapeutic potential of human milk oligosaccharides (HMOs) in mitigating age-related intestinal barrier dysfunction using D-galactose-induced aging mouse model. Methods: Aging was induced in mice via chronic intraperitoneal administration of D-galactose (450 mg/kg body weight [BW]) for 8 weeks. Concurrently, mice were orally administered HMOs—2'-fucosyllactose (2'-FL), 3'-sialyllactose (3'-SL), and lacto-N-neotetraose (LNnT)—at a dose of 500 mg/kg BW daily. After 8 weeks, the body weight changes, intestinal organ indices, oxidative stress levels, intestinal permeability, colonic morphology, and the proliferation and differentiation capabilities of stem cells in mice were measured and analyzed. Results: Following HMOs intervention, aging model mice demonstrated a pronounced recovery of intestinal health, with organ indices exhibiting a significant increase of 27.16%~33.74% (P<0.05). Serum superoxide dismutase activity increased significantly by 34.82%~99.83% (P<0.001), while malondialdehyde content decreased by 46.21%~61.79% (P<0.05 or P<0.01). Intestinal barrier integrity was reinforced, with FITC-dextran permeability decreasing by 48.45~62.84% (P<0.05 or P<0.01). Histological analyses revealed remarkable regenerative effects on colonic architecture, including significant increased in crypt number, crypt depth, proliferating cell nuclear antigen (PCNA)-positive cell counts, and cell differentiation (P<0.05 or P<0.01). Conclusion: HMOs intervention, particularly with 2'-FL, significantly enhanced the proliferation and differentiation capabilities of intestinal stem cells in D-galactose-induced aging mice. It improved the atrophy of colonic crypt morphology, strengthened the intestinal mucus barrier, and reduced intestinal permeability, thereby ameliorating the aging intestinal barrier.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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