*Article* **Comparative Study of** *Sargassum fusiforme* **Polysaccharides in Regulating Cecal and Fecal Microbiota of High-Fat Diet-Fed Mice**

**Bin Wei 1,2,†, Qiao-Li Xu 2,†, Bo Zhang 2, Tao-Shun Zhou 2, Song-Ze Ke 2, Si-Jia Wang 2,3, Bin Wu 4, Xue-Wei Xu 1,\* and Hong Wang 2,\***


**Abstract:** Seaweed polysaccharides represent a kind of novel gu<sup>t</sup> microbiota regulator. The advantages and disadvantages of using cecal and fecal microbiota to represent gu<sup>t</sup> microbiota have been discussed, but the regulatory effects of seaweed polysaccharides on cecal and fecal microbiota, which would benefit the study of seaweed polysaccharide-based gu<sup>t</sup> microbiota regulator, have not been compared. Here, the effects of two *Sargassum fusiforme* polysaccharides prepared by water extraction (SfW) and acid extraction (SfA) on the cecal and fecal microbiota of high-fat diet (HFD) fed mice were investigated by 16S rRNA gene sequencing. The results indicated that 16 weeks of HFD dramatically impaired the homeostasis of both the cecal and fecal microbiota, including the dominant phyla Bacteroidetes and Actinobacteria, and genera *Coriobacteriaceae*, *S24-7*, and *Ruminococcus*, but did not affect the relative abundance of Firmicutes, *Clostridiales*, *Oscillospira*, and *Ruminococcaceae* in cecal microbiota and the Simpson's index of fecal microbiota. Co-treatments with SfW and SfA exacerbated body weight gain and partially reversed HFD-induced alterations of *Clostridiales* and *Ruminococcaceae*. Moreover, the administration of SfW and SfA also altered the abundance of genes encoding monosaccharide-transporting ATPase, α-galactosidase, β-fructofuranosidase, and β-glucosidase with the latter showing more significant potency. Our findings revealed the difference of cecal and fecal microbiota in HFD-fed mice and demonstrated that SfW and SfA could more significantly regulate the cecal microbiota and lay important foundations for the study of seaweed polysaccharide-based gu<sup>t</sup> microbiota regulators.

**Keywords:** *Sargassum fusiforme* polysaccharides; high-fat diet; cecal microbiota; fecal microbiota; 16S rRNA gene sequencing
