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Inflammaging refers to chronic, low-grade inflammation during aging, which contributes to the pathogenesis of age-related diseases. Studies have shown that probiotic intervention in the aging stage could delay aging-related disorders. However, whether the application of probiotics in early life could have antiaging effects on offspring was unknown. Here, we investigated the effects of  Lactobacillus rhamnosus GG  ( LGG ) colonization in early life on inflammaging of offspring. Pregnant mice with the same conception time were given  LGG  live bacteria (LC group) or  LGG  fixed bacteria (NC group) from the 18th day after pregnancy until natural birth. The progeny mice were treated with 10 7  cfu of live or fixed LGG for 0-5 days after birth, respectively.  LGG  colonization could be detected in the feces of 3-week offspring. The 16S rRNA sequencing analysis of 3-week-old offspring showed that colonization of  LGG  in early life could alter the composition and diversity of gut microbiota. Interestingly, the beneficial effects of  LGG  colonization in early life on the microbiota lasted to 8 months old. The abundance of longevity-related bacteria ( Lactobacillus ,  Bifidobacterium , and  Akkermansia muciniphila ) increased significantly in the  LGG  colonization group. In addition,  LGG  colonization increased the abundance of short-chain fatty acid- (SCFA-) producing bacteria and the production of cecal SCFAs.  LGG  colonization in early life protected the intestinal barrier, enhanced antioxidant defense, attenuated epithelial cell DNA damage, and inhibited intestinal low-grade inflammation in 8-month-old progeny mice. Mechanically,  LGG  could upregulate Sirtuin1 (SIRT1)/Adenosine 5′-monophosphate-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor  γ  coactivator 1- α  (PGC-1 α ) pathway and repress activation of nuclear factor-kappa B (NF- κ B), while the protective effect of  LGG  was blunted after SIRT1 gene silencing. Together,  LGG  colonization in early life could ameliorate inflammaging of offspring, which would provide a new strategy for the prevention of age-related diseases.

Lactobacillus rhamnosus GG Colonization in Early Life Ameliorates Inflammaging of Offspring by Activating SIRT1/AMPK/PGC-1α Pathway