Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach.

Yuying Chen,Yang Dai,Qiang Zhang,Yinwen Fan,Xin Ding,Junhong Wang,Yujia Chen,Mingming Zhang,Yougui Yang

doi:10.3389/fcimb.2021.781132

Abstract

Hookworm is one type of soil-transmitted helminth, which could exert an anti-inflammatory effect in human or animal host, which provides a beneficial possibility for the discovery of inflammatory-related disease interventions. The identification of hookworm-derived anti-inflammatory molecules is urgently needed for future translational research. The emergence of metabolomics has become a powerful approach to comprehensively characterize metabolic alterations in recent times. Herein, excretory and secretory products (ESPs) were collected from cultured adult worm, while small intestinal contents were obtained from Nippostrongylus brasiliensis (N. brasiliensis, Nb)-infected mice. Through ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) platform, metabolomics analysis was used to explore the identification of anti-inflammatory molecules. Out of 45 differential metabolites that were discovered from ESPs, 10 of them showed potential anti-inflammatory properties, which could be subclassed into amino acids, furanocoumarins, linear diarylheptanoids, gamma butyrolactones, and alpha-keto acids. In terms of intestinal contents that were derived from N. brasiliensis-infected mice, 14 out of 301 differential metabolites were discovered to demonstrate anti-inflammatory effects, with possible subclassification into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. Furthermore, nine of the differential metabolites appeared both in ESPs and infected intestinal contents, wherein four were proven to show anti-inflammation properties, namely, L-glutamine, glutamine (Gln), pyruvate, and alanine-Gln (Ala-Gln). In summary, we have provided a method for the identification and analysis of parasite-derived molecules with potential anti-inflammatory properties in the present study. This array of anti-inflammatory metabolites could provide clues for future evaluation and translational study of these anti-inflammatory molecules.

Highlights

As a soil-transmitted helminth, hookworm has been implicated in the incidence of several conditions, namely, iron deficiency anemia (IDA), malnutrition, and other chronic health problems, which are defined by intensity of infection in human host, wherein they can cause impaired physical and cognitive development as well as adverse outcome of pregnancy and lethargy (Loukas et al, 2016)
Analysis of peaks that were excerpted from the entire experimental and QC samples was performed using the principal component analysis (PCA) method with results shown in Supplementary Figure S1, wherein outliers were obviously seen in the samples of positive and negative ion modes, while those of the QC were clustered closely
Available evidence suggests that hookworm could exert an antiinflammation property for their long-term survival in human or animal host, which may in turn provide a beneficial effect against inflammatory-related diseases (Ferreira et al, 2017; Lothstein and Gause, 2021)

Summary

Introduction

As a soil-transmitted helminth, hookworm has been implicated in the incidence of several conditions, namely, iron deficiency anemia (IDA), malnutrition, and other chronic health problems, which are defined by intensity of infection in human host, wherein they can cause impaired physical and cognitive development as well as adverse outcome of pregnancy and lethargy (Loukas et al, 2016). With a major burden of hookworm infection in areas described above, epidemiological evidence showed that a negative correlation was observed between hookworm infection and occurrence/frequency of inflammatory diseases such as metabolic disorders, allergic conditions, and inflammatory bowel disease (IBD), which could be defined as “hygiene hypothesis” (Maizels et al, 2004; Briggs et al, 2016; Ryan et al, 2020) Guided by this hypothesis, numerous studies of helminthbased therapy for different inflammatory disease models have been explored in recent years, wherein it was found that derived products of helminths showed drug-like anti-inflammatory activities in human, mice, and other larger animals (Summers et al, 2005; McSorley et al, 2012; Scholmerich et al, 2017). Identification and evaluation of helminth-derived molecules as anti-inflammatory agents are urgently needed for future translational research

Methods

Results

Conclusion