Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota

Abstract

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

“…Previous studies have shown ( Yin et al, 2016 ; Qian et al, 2020 ) that nsPEF, as a local treatment, can stimulate a systemic immune activation effect and prevent HCC from metastasizing in the liver and developing in distant areas. There have been microecological studies suggesting that the microecology and metabolism of the digestive tract play an important role in this process ( Dong et al, 2021 ).…”

“…Our innovation is to confirm the effectiveness of nsPEFs as a new generation of minimally invasive ablation tools for HCC through gut microbiome and serum metabonomics analysis. In the study by Dong et al, pigs were treated with nsPEFs, and the effects of nsPEFs on serum metabolism and gut microbiome were observed by multiomics analysis ( Dong et al, 2021 ). However, their research focused on the metabolic changes associated with liver injury and the changes in microflora pre- and post-treatment, and there was no animal model of HCC.…”

“…As a substantial organ of the human body, the liver participates in a variety of metabolic reactions, and the destruction of hepatocytes is often accompanied by the abnormality of serum biochemical indexes. It has been reported that liver function will be enhanced temporarily within a few days after nsPEF ablation and return to normal after 7 days ( Dong et al, 2021 ). For the HCC mice, whether it will also cause transient liver injury after nsPEF ablation and the duration of liver injury remain to be explored.…”