Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula

Shasha He; Chunxia Zhao; Yuhong Guo; Jingxia Zhao; Xiaolong Xu; Yahui Hu; Bo Lian; Haoran Ye; Ning Wang; Lianxiang Luo; Qingquan Liu

doi:10.3389/fmicb.2023.1111962

Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula

Front Microbiol. 2023 Mar 8:14:1111962. doi: 10.3389/fmicb.2023.1111962. eCollection 2023.

Authors

Shasha He^{1

2

3}, Chunxia Zhao^{1

2

3}, Yuhong Guo^{1

2

3}, Jingxia Zhao^{1

2

3}, Xiaolong Xu^{1

2

3}, Yahui Hu^{2

3

4}, Bo Lian⁵, Haoran Ye^{1

2

3}, Ning Wang^{1

2}, Lianxiang Luo⁶, Qingquan Liu^{1

2

3}

Affiliations

¹ Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
² Beijing Institute of Chinese Medicine, Beijing, China.
³ Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, China.
⁴ Tianjin University of Traditional Chinese Medicine, Tianjin, China.
⁵ Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
⁶ The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China.

Abstract

Sepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1β. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.

Keywords: Shen FuHuang formula; gut microbiome; metabonomics; sepsis; traditional Chinese medicine.