Yuguang He

Background: Natto, a well-known fermented soybean product beneficial for bone health, remains unclear in its mechanism. Methods: This study investigated its effect on secondary osteoporosis (OP) in mice. Results: Natto significantly inhibited weight loss, bone quality deterioration, and bone morphological damage, and regulated OPG/RANKL pathway protein expression (p < 0.05) in OP mice. Analysis of 16S rRNA revealed that natto increased gut microbiota α-diversity and the abundance of Sutterella, Roseburia, and Coprococcus, while reducing harmful bacteria such as Streptococcus, Shigella, and Helicobacter. These microbial changes positively correlated with body weight, bone size, and serum osteogenic metabolism in OP mice. Serum metabolomics showed differential metabolites of the natto group enriched in PPAR signaling and primary bile acid biosynthesis. Verification by mRNA and ELISA indicated that the upregulated liver and circulating PPARα by natto may regulate downstream bile acid pathways, linking gut microbiota to multi-organ metabolic functions. Conclusions: In summary, natto may act on gut microbiota to alleviate bone loss via the “gut microbiota–bile acid–OPG/RANKL” network, targeting multiple organs including gut, liver, and bone. This provides a theoretical basis for natto dietary intervention in osteoporosis prevention through the gut–bone axis.

Obesity is characterized by abnormal adipose tissue expansion and energy metabolism imbalance. Browning of white adipose tissue (WAT), wherein white adipocytes acquire thermogenic properties similar to brown adipose tissue, represents a key mechanism for increasing energy expenditure. Although ginseng (Panax ginseng C.A. Meyer) is widely recognized as a health-promoting botanical, its role in WAT browning has not been fully elucidated. This review summarizes evidence that ginseng and its bioactive components regulate major thermogenic pathways, including β-adrenergic/cyclic adenosine monophosphate-protein kinase (cAMP-PKA) signaling, AMP-activated protein kinase (AMPK), and the peroxisome proliferator-activated receptor γ (PPARγ)/coactivator 1α (PGC-1α) axis, thereby upregulating key markers such as uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and type II iodothyronine deiodinase (DIO2). These effects promote mitochondrial function and fatty acid oxidation, reduce lipogenesis, alleviate inflammation, and improve insulin sensitivity, collectively fostering a microenvironment conducive to browning. Furthermore, fermentation has been found to enhance the bioactivity and thermogenic efficacy of ginseng. Recent evidence indicates that gut microbiota and their metabolites—such as short-chain fatty acids, unsaturated fatty acids, and bile acids—play a notable role in ginseng-induced thermogenesis via receptors including G-protein-coupled receptor 41/43 (GPR41/43), takeda G-protein-coupled receptor 5 (TGR5), and farnesoid X receptor (FXR). These multi-organ interaction networks involving the gut–fat, gut–liver, and gut–brain axes reflect the role of ginseng in integrating systemic metabolism. In summary, this review discusses the multi-level regulatory network through which ginseng promotes WAT browning, providing a mechanistic basis for its potential application in body weight and metabolic health management.

As one of the few carotenoid-producing microorganisms, Rhodotorula mucilaginosa remains underexplored for its antioxidant activity. This study investigated the effects of R. mucilaginosa JAASSRY on D-galactose-induced aging mice. The high-dose JAASSRY (HR) significantly increased body weight by 9.89% compared to the model group (AM), while reducing organ indices of the spleen, liver, kidneys, and brain (p < 0.01). Compared with the AM group, the HR group exhibited increased serum activities of SOD (20.26%), GSH-Px (9.03%), and CAT (133.01%), with a 24.87% decrease in MDA level. In brain tissue, SOD, GSH-Px, and CAT activities increased by 79.49%, 8.45%, and 60.23%, respectively, while MDA decreased by 8.29%. R. mucilaginosa JAASSRY also dose-dependently alleviated structural damage in the hippocampus and spleen and improved motor strength and learning-memory capacity. Furthermore, R. mucilaginosa JAASSRY increased the abundance of Lactobacillus and reduced Proteobacteria, Helicobacter, and Oscillospira, while enhancing antioxidant capacity by modulating nucleotide, lipid, and carbohydrate metabolism. Lactobacillus and Pediococcus were positively correlated with memory latency and CAT/SOD activities (p < 0.05), whereas Actinormyces and Dehalobacterium showed negative correlations. Notably, HR performed comparably or superiorly to β-carotene in improving cerebral oxidative stress and beneficial microbiota, suggesting its potential in neuroprotection and gut–brain axis regulation. In conclusion, R. mucilaginosa JAASSRY mitigates aging-related oxidative damage and behavioral deficits by modulating gut microbiota structure and function, demonstrating its promise as a β-carotene alternative in animal husbandry and functional foods.