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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 based on high-intensity electric voltage to achieve tumor-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys, and other organs with rich blood supply. When we were looking at the safety and feasibility of applying nsPEF on porcine livers, we found that the indicators of liver function after ablation fluctuated. To further study the influence of this technique in the treatment of liver, we collected serum and fecal specimens of the pigs pre-treatment and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analyzing 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Yeping Dong

PROVIDER: MTBLS2406 | MetaboLights | 2021-06-21

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS2406	Other
	FILES	Other
	a_MTBLS2406_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS2406_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt

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Project description:Background & Aims: Non-alcoholic fatty liver disease (NALFLD)-associated changes in gut microbiota are important drivers of disease progression toward fibrosis. Therefore, reversing microbiota alterations could ameliorate NAFLD progression. Oat beta-glucan, a non-digestible polysaccharides, has shown promising therapeutic effects on hyperlipidemia associated with NAFLD, but its impact on gut microbiota and most importantly NAFLD fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping including body composition, glucose tolerance, and lipid metabolism as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of NAFLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota was modulated using broad-spectrum antibiotic (Abx) treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened NAFLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon Abx treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of TLR ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced NAFLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing NAFLD progression and should be assessed in clinical studies.

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

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