Fermented Polygonatum kingianum polysaccharide exerts enhanced anti-obesity effects by modulating the gut microbiota-GDCA-TGR5 axis.

Abstract

Probiotic-fermented Polygonatum kingianum polysaccharide (FPKP0) was previously confirmed to exhibit enhanced anti-adipogenic activity in 3T3-L1 cells in vitro owing to altered structural, prompting an examination of whether this modified FPKP0 exerts superior anti-obesity effects in vivo via related mechanism in high-fat diet-fed mice. Physiological results showed that FPKP0 outperformed unfermented PKP0 accounting for reducing body weight, improving blood lipids, alongside alleviating hepatic steatosis and colonic damage. Correspondingly, FPKP0 reshaped the gut microbiota by boosting beneficial genera (especially Akkermansia muciniphila) and suppressing harmful bacteria (e.g., Dubosiella, Helicobacter). Integrated metagenomic and metabolomic analyses identified A. muciniphila and Glycodeoxycholic acid (GDCA) as the key microbial and metabolic factors with the in vivo effects of FPKP0. A strong positive correlation (ρ = 0.83) between A. muciniphila abundance and GDCA levels suggests a potential relationship between microbial remodeling and bile acid metabolism following FPKP0 intervention. Further mechanistic exploration suggested that TGR5 may serve as a downstream receptor associated with FPKP0-related changes in GDCA. Molecular docking and immunoblotting indicated a GDCA-TGR5 interaction and activation of the Gsα-PKA-CREB-UCP1 cascade to stimulate energy expenditure. This enhanced in vivo anti-obesity effect of FPKP0 may involve modulation of the gut microbiota (AKK)-bile acid (GDCA)-TGR5 axis, supporting the potential of FPKP0 as a functional food additive to combat obesity and related disorders.