2'-Fucosyllactose Ameliorates Oxidative Stress Damage in d-Galactose-Induced Aging Mice by Regulating Gut Microbiota and AMPK/SIRT1/FOXO1 Pathway

Abstract

The imbalance of reactive oxygen species is the main cause in aging, accompanied by oxidative stress. As the most abundant in human milk oligosaccharides (HMOs), 2'-Fucosyllactose (2'-FL) has been confirmed to have great properties in immunity regulation and anti-inflammatory. The research on 2'-FL is focused on infants currently, while there is no related report of 2'-FL for the elderly. A d-galactose-induced accelerated aging model was established to explore the protective effect of 2'-FL on the intestines and brain in mice. In this study, 2'-FL significantly reduced oxidative stress damage and inflammation in the intestines of aging mice, potentially by regulating the sirtuin1 (SIRT1)-related and nuclear factor E2-related factor 2 (Nrf2) pathways. In addition, 2'-FL significantly improved the gut mucosal barrier function and increased the content of short-chain fatty acids (SCFAs) in the intestine. The gut microbiota analysis indicated that 2'-FL mainly increased the abundance of probiotics like Akkermansia in aging mice. Moreover, 2'-FL significantly inhibited apoptosis in the brains of aging mice, also increasing the expression of SIRT1. These findings provided a basis for learning the benefits of 2'-FL in the aging process.

Keywords: 2′-fucosyllactose; SIRT1; aging; gut microbiota.

Figure 1

Effects of 2′-fucosyllactose (2′-FL) on oxidative stress. Letters a, b, and c indicated significant differences between groups (p < 0.05).

Figure 2

Effects of 2′-FL on the gut mucosal barrier. (a) Immunohistochemistry of the mucous layer (MUC2, zoom in 100×; circles indicate the expression of MUC2). (b) Expression of mucoprotein and tight junction proteins at the gene level. Letters a, b, and c indicated significant differences between groups (p < 0.05).

Figure 3

Effects of 2′-FL on inflammation and the nuclear factor E2-related factor 2 (Nrf2) signaling pathway in the colon. (a) Expression of inflammatory cytokines at the gene level. (b) Expression of the Nrf2 signaling pathway at the gene level. Letters a, b, and c indicated significant differences between groups (p < 0.05).

Figure 4

Effects of 2′-FL on longevity pathways. (a) Gene and protein expressions of the AMPK/SIRT1/FOXO1 pathway in the colon. (b) Expression of G-protein-coupled receptors (GPRs) in the colon at the gene level. (c) Content of short-chain fatty acids (SCFAs) in the colon contents. Letters a and b indicated significant differences between groups (p < 0.05).

Figure 5

Analysis of the gut microbiota in all three groups. (a) The level of phylum. (b) The level of genus. (c) Dilution curve. (d) Tax4Fun analysis in level 2 based on the SILVA database. (e) Pearson analysis at the genus level. * p < 0.05, ** p < 0.01, and *** p < 0.001. (f) Pearson analysis at the species level. * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 6

Effects of 2′-FL on inflammation, longevity, and apoptosis in the brain. (a) H&E staining of the hippocampus (zoom in 100×; arrows indicate inflammatory infiltration). (b) Expression of apoptosis at the gene level. (c) Expression of the SIRT1/FOXO1 pathway at the gene level. Letters a and b indicated significant differences between groups (p < 0.05).