Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites' Identification, Network Pharmacology, and Experimental Validation.

Qin Wang,Yao Wang,Chang Li,He Zhuang,Nan Ma,Yue-Hu Pei,Xing-Hua Zhang,Ya-Jing Wang,Shu-Lin Liu,Yu-Jie Zhou

doi:10.3389/fphar.2021.706220

Qin Wang, Yao Wang + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2021.706220

Copy DOI

Abstract

Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K–Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.

Highlights

The human gut microbiota is composed of an enormous diversity of microorganisms, including bacteria, fungi, and other microbes, which together play important roles in maintaining the dynamic homeostatic and healthy micro-environment of the host (Johnson et al, 2016; Thomas et al, 2017; Liang et al, 2018)
We describe the anticancer activities of gut bacterial strain AD16, the isolation and structural elucidation of five new compounds, along with nine known ones via bioactivity-guided isolation, and the network analysis of the compounds from AD16
The Cell Counting Kit (CCK)-8 result of A549 cells incubated with AD16 demonstrated that the effects of AD16 were dose- and time-dependent against A549 as judged by cell proliferation percentages in comparison with the control (Figure 1B)

Summary

INTRODUCTION

The human gut microbiota is composed of an enormous diversity of microorganisms, including bacteria, fungi, and other microbes, which together play important roles in maintaining the dynamic homeostatic and healthy micro-environment of the host (Johnson et al, 2016; Thomas et al, 2017; Liang et al, 2018). Our previous research suggested that the composition of the gut microbiota in lung cancer patients was radically different from that of healthy individuals, which had a higher abundance of bacteria of phylum Actinobacteria compared to the lung cancer patients (Zhuang et al, 2019). This finding prompted us to isolate more Actinobacteria from the human gut (Zhou et al, 2017). We describe the anticancer activities of gut bacterial strain AD16, the isolation and structural elucidation of five new compounds, along with nine known ones via bioactivity-guided isolation, and the network analysis of the compounds from AD16. This work demonstrated that gut microbiota is a rich source of potential cancer therapeutics for further studies and future clinical applications

MATERIALS AND METHODS

RESULTS AND DISCUSSIONS

DATA AVAILABILITY STATEMENT

ETHICS STATEMENT