This study aimed to explore the effect of 2′-Fucosyllactose (2′-FL) on the gut health of aged mice. The results revealed that 2′-FL intervention effectively improved the intestinal permeability and reduced the serum diamine oxidase (DAO) level in aged mice (
p < 0.05); in addition, 2′-FL increased the IgA level and decreased the IgG level (
p < 0.05). Meanwhile, 2′-FL reduced the serum levels of IL-6, IL-1β, TNF-α, and IFN-γ (
p < 0.05). Histopathological analysis indicated that 2′-FL successfully reversed intestinal damage in the jejunum and colon. Additionally, 2′-FL increased the expression of the tight-junction proteins ZO-1 and Claudin-1 both at mRNA and protein levels (
p < 0.05), and also down-regulated the expression of pro-inflammatory factors (IL-6, IL-1β) (
p < 0.05), and decreased aging-related markers P16
INK4α and P21
Cip1. Furthermore, 16S rRNA results showed that 2′-FL increased the relative abundance of beneficial bacteria in the gut, such as
Lachnospiraceae_UCG-006, norank_f__
Muribaculaceae and
Lachnospiraceae_NK4A136_group. In conclusion, 2′-FL effectively improved the intestinal immune health of the aged mice and provided a theoretical basis for its application as a functional component in the treatment of intestinal diseases.
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