Serum-based untargeted metabolomics to investigate possible indicators of asymptomatic Lymphatic Filariasis

Abstract

Introduction

Lymphatic filariasis (LF), a devastating tropical disease caused by the parasitic filarial worms Wuchereria bancrofti, Brugia malayi, and Brugia timori, continues to pose a substantial public health challenge in endemic tropical and subtropical regions. After malaria, it is the second most prevalent vector-borne illness. A wide range of clinical manifestations are associated with LF. The clinical symptoms of LF are varied, ranging from asymptomatic or subclinical infections with circulating microfilariae to pronounced pathologies such as lymphedema, elephantiasis, and hydrocele. The diagnosis of asymptomatic LF infections can be challenging since microscopy, serological tests, and antigen detection tests may exhibit decreased sensitivity in certain instances.

Methods

Serum samples were collected from 84 microfilaremic individuals and 48 healthy volunteers residing in the endemic districts of Eastern Uttar Pradesh. The serum samples were processed, and the metabolites were extracted and identified via High-Resolution Accurate Mass Spectrometry (HRAMS)-based metabolomics. Metabolomic data analysis was conducted using the default parameters of "Compound Discoverer 3.3.3.20" software. A two-tailed Student's t-test was employed to assess feature differences between healthy and microfilaremic groups. The p-value was adjusted using the Benjamini–Hochberg correction for false discovery rate (FDR). A p-value of <0.05 was regarded as statistically significant. The "MetaboAnalyst 6.0" platform was utilized for pathway and network analyses.

Results

A total of 161 metabolites were uncovered, with 24 exhibiting significant upregulation and 137 exhibiting significant downregulation. Multivariate and univariate statistical analysis demonstrated significant metabolic differences distinguishing microfilaremic individuals from healthy controls. Additionally, pathway analysis of the metabolites showed changes in the metabolism of arachidonic acid and unsaturated fatty acid synthesis. Network analysis identified metabolites that had significant clinical implications.

Conclusions

The findings indicate an alteration in the host serum metabolome during the microfilaremic stage of lymphatic filariasis, which could function as possible biomarkers for early disease detection, surveillance, and therapeutic intervention.