Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

Xiaoqing Fan; Chutian Mai; Ling Zuo; Jumin Huang; Chun Xie; Zebo Jiang; Runze Li; Xiaojun Yao; Xingxing Fan; Qibiao Wu; Peiyu Yan; Liang Liu; Jianxin Chen; Ying Xie; Elaine Lai-Han Leung

doi:10.1016/j.apsb.2022.10.016

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

Acta Pharm Sin B. 2023 Mar;13(3):1164-1179. doi: 10.1016/j.apsb.2022.10.016. Epub 2022 Oct 22.

Authors

Xiaoqing Fan¹, Chutian Mai¹, Ling Zuo², Jumin Huang¹, Chun Xie³, Zebo Jiang⁴, Runze Li⁵, Xiaojun Yao¹, Xingxing Fan¹, Qibiao Wu¹, Peiyu Yan¹, Liang Liu⁵, Jianxin Chen², Ying Xie⁵, Elaine Lai-Han Leung³

Affiliations

¹ Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China.
² Beijing University of Chinese Medicine, Beijing 100029, China.
³ Cancer Center, Faculty of Health Science; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau 999078, China.
⁴ Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
⁵ State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China.

Abstract

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10⁺ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10⁺ M2 macrophage production.

Keywords: 16S PacBio SMRT sequencing; BaWeiBaiDuSan; Interleukin-10; Lactobacillus johnsonii; Macrophages; Network pharmacology; Sepsis-induced liver injury.