# Fermented Red Ginseng Restores Age-Associated Insulin Homeostasis and Gut Microbiome Balance in Mice

## TL;DR

Fermented red ginseng helps older mice by improving insulin balance and restoring gut bacteria balance.

## Contribution

FRG is shown to restore insulin homeostasis and gut microbiome balance in aged mice.

## Key findings

- FRG improved insulin homeostasis by activating AKT and PRAS40 in the liver.
- FRG reduced proinflammatory cytokines and liver inflammation in aged mice.
- FRG enriched beneficial gut bacteria and reduced harmful ones in aged mice.

## Abstract

The goal of this study was to investigate the potential role of fermented red ginseng (FRG) in mitigating age-associated disruptions in insulin homeostasis and gut microbiome composition using 19-month-old aged male mice. Together with the improved insulin homeostasis, FRG supplementation activated insulin-related signaling pathways and suppressed proinflammatory cytokines in the liver. In addition, we found that FRG showed a pronounced influence on the microbial community by restoring the balance between commensal and opportunistic bacteria that is compromised during aging. Taken together, our findings highlight that FRG positively impacts the aging process by preserving insulin homeostasis and gut microbiota compositional equilibrium.

Biological aging disrupts liver–gut intercommunication, resulting in the development of insulin resistance and type 2 diabetes, coupled with the imbalance of gut microbiome composition known as gut dysbiosis. Fermented red ginseng (FRG) is a renowned functional food substance showing its notable anti-inflammatory and anti-diabetic effects owing to its unique bioactive compounds known as ginsenosides. However, whether FRG could impact biological aging and age-related metabolic dysfunction is still unclear. The current study aimed to determine the health benefits of FRG in improving age-associated impaired insulin homeostasis and gut dysbiosis in 19-month-old male mice. Mice were fed with a normal chow diet (NCD) or NCD with FRG (300 mg/kg) for 14 weeks. FRG supplementation significantly improved insulin homeostasis by activating the hepatic protein kinase B (AKT) and proline-rich AKT substrate of 40 kDa (PRAS40). We also observed suppressed mRNA expression of proinflammatory cytokines and diminished inflammatory infiltrates in the liver of FRG-fed mice compared with NCD-only controls. Furthermore, alongside a decreased ratio of Firmicutes to Bacteroidetes, FRG administration enriched beneficial genera, including Muribaculaceae, Borkfalkiaceae, Parasutterella, and Clostridia vadin BB60 group, whereas FRG reduced the abundance of Erysipelotrichaceae and Dubosiella at the genus level. In summary, we suggest that FRG can be a potential anti-aging dietary supplement to manage age-driven dysregulation of insulin homeostasis and gut microbiota composition.