Morus alba L. fruit, a medicinal and edible fruit in East Asia, showed potential health-promoting effects against metabolic syndrome (MetS). However, both the protective effects and mechanisms of different fractions extracted from Morus alba L. fruit against MetS remain unclear. Additionally, the gut microbiota and its metabolites are regarded as key factors in the development of MetS. This study aimed to investigate the potential role of polyphenols and polysaccharides derived from Morus alba L. fruit against MetS in high-fat diet (HFD)-fed mice, individually and in combination, focusing on remodeling effects on gut microbiota and metabolite profiles. In the study, polyphenols and polysaccharides derived from Morus alba L. fruit improved the traditional pharmacodynamic parameters of MetS, including reductions in body weight (BW) and fat accumulation, improvement in insulin resistance, regulation of dyslipidemia, prevention of pathological changes in liver, kidney and proximal colon tissue, and suppressive actions against oxidative stress. In particular, the group treated with polyphenols and polysaccharides in combination showed better efficacy. The relative abundance of beneficial bacterial genera Muribaculum and Lachnospiraceae_NK4A136_group were increased to various degrees, while opportunistic pathogens such as Prevotella_2, Bacteroides, Faecalibacterium and Fusobacterium were markedly decreased after treatments. Moreover, fecal metabolite profiles revealed 23 differential metabolites related to treatments with polyphenols and polysaccharides derived from Morus alba L. fruit, individually and in combination. Altogether, these results demonstrated that polyphenols and polysaccharides derived from Morus alba L. fruit attenuated MetS in HFD-fed mice, and improved the gut microbiota composition and fecal metabolite profiles.

Mori Fructus, rich in polysaccharides and polyphenols, has long been used in East Asia as a functional food and medicinal agent. In traditional Chinese medicine, it is used to treat various ailments like wasting-thirst syndrome and constipation. Studies suggest its extract fractions may alleviate metabolic syndrome symptoms by affecting gut microbiota. To explore this, fecal microbiota transplantation (FMT) was used in an experiment. Pseudo-germ-free mice were created with antibiotics and given a high-fat, high-sugar diet (HFD) to induce metabolic syndrome. Then, fecal bacterial infusions were transplanted. Results showed significant improvement in metabolic syndrome parameters in the FMT-MFPS(fecal microbiota transplantation-Mori Fructus polyphenols plus polysaccharides) group. Dyslipidemia, liver, and kidney injuries were modulated in treated mice. The PPARα/PGC-1α signaling pathway was activated. These findings indicate Mori Fructus extract fractions prevent metabolic syndrome via gut microbiota modulation, with effects sustained through FMT, providing a reference for prevention.