Tingting Liu ¹ Xiaodong Ge ² Lu Song ³ Huanhuan Wu ⁴ Xue Qian ¹ Bowen Jia ¹ Chao Zhao ^5* Yi Zhuang ^6*

• ¹ The Second People’s Hospital of Yancheng, Yancheng, China
• ² Yancheng Institute of Technology, Yancheng, Jiangsu, China
• ³ The First People’s Hospital of Yancheng, Yancheng, China
• ⁴ Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, Jiangsu Province, China
• ⁵ Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China
• ⁶ Nanjing Drum Tower Hospital, Nanjing, China

We would like to submit the enclosed manuscript entitled "Zingiber striolatum phytochemicals ameliorated hyperglycemia symptoms by modulating gut microbial communities in mice with type 2 diabetes mellitus", which we wish to be considered for publication in "Frontiers in Nutrition". I can confirm that all co-authors have seen and agreed with the contents of the manuscript and there is no financial interest to report. I also certify that the submission is not under review at any other publication.Zingiber striolatum is a common food ingredient, and contains bioactive compounds such as polysaccharides, volatile oils, flavonoids, and natural pigments. In our previous study, we found that Zingiber striolatum ethanol extract (ZSE) could inhibit the activity of α-glucosidase in vitro, which showed potential hypoglycemic activity. However, the regulatory influence of ZSE on the gut microbiota of T2DM mice or its potential relationship with T2DM pathology remains unexplored. In this study, a T2DM mouse model was employed to assess the effects of ZSE on hyperglycemia symptoms. After a 4-week intervention, ZSE significantly ameliorated fasting blood glucose (FBG), area under the curve of oral glucose tolerance test (AUC of OGTT) and glycated serum protein (GSP) in T2DM mice. Moreover, the high-dose (ZSE-H) treatment increased the relative abundance of beneficial bacteria such as Faecalibaculum, while reducing harmful bacteria such as Bilophila, thereby alleviating insulin resistance. Additionally, ZSE-H demonstrated superior efficacy over low-dose (ZSE-L) in improving FBG, AUC of OGTT, and other hypoglycemic parameters. Predictive analysis of the correlation between gut microbiota and hypoglycemic parameters identified Dubosiella, Bacillus, and Mailhella as potential microbial biomarkers for further investigation into the pathogenesis of T2DM. In summary, ZSE plays a pivotal role in mitigating hyperglycemia in T2DM mice through the modulation of intestinal microbiota communities. We believe that our findings could arouse the interest of Frontiers in Nutrition readers in the aspect of ethanol extract to improve hypoglycemic activity and gut microbiota.We deeply appreciate your consideration of our manuscript, and we look forward to receiving comments from the reviewers. Thank you very much.