*Article* **Synergistic Effects of the Jackfruit Seed Sourced Resistant Starch and** *Bifidobacterium pseudolongum* **subsp.** *globosum* **on Suppression of Hyperlipidemia in Mice**

**Zeng Zhang 1, Yuanyuan Wang 1, Yanjun Zhang 2, Kaining Chen 3, Haibo Chang 1, Chenchen Ma 1, Shuaiming Jiang 1, Dongxue Huo 1, Wenjun Liu 4, Rajesh Jha <sup>5</sup> and Jiachao Zhang 1,5,\***


**Abstract:** Approximately 17 million people suffer from cardiovascular diseases caused by hyperlipidemia, making it a serious global health concern. Among others, resistant starch (RS) has been widely used as a prebiotic in managing hyperlipidemia conditions. However, some studies have reported limited effects of RS on body weight and blood lipid profile of the host, suggesting further investigation on the synergistic effects of RS in combination with probiotics as gut microbes plays a role in lipid metabolism. This study evaluated the effects of jackfruit seed sourced resistant starch (JSRS) as a novel RS on mice gut microbes and hyperlipidemia by performing 16s rRNA and shotgun metagenomic sequencing. The results showed that 10% JSRS had a limited preventive effect on bodyweight and serum lipid levels. However, the JSRS promoted the growth of *Bifidobacterium pseudolongum*, which indicated the ability of *B. pseudolongum* for JSRS utilization. In the validation experiment, *B. pseudolongum* interacted with JSRS to significantly reduce bodyweight and serum lipid levels and had a therapeutic effect on hepatic steatosis in mice. Collectively, this study revealed the improvements of hyperlipidemia in mice by the synergistic effects of JSRS and *B. pseudolongum*, which will help in the development of "synbiotics" for the treatment of hyperlipidemia in the future.

**Keywords:** hyperlipidemia; resistant starch; *Bifidobacterium pseudolongum*; gut microbes; synbiotics
