Lymphatic filariasis, caused by Brugia malayi, leads to chronic lymphatic dysfunction and lymphedema. The molecular mechanisms underlying interactions between filarial worms and their hosts remain poorly understood. Using untargeted metabolomics, we identify previously unknown acetylcholine analogs synthesized from leucine and isoleucine that are secreted by Brugia adult males. In the mammalian host, these metabolites selectively activate host M2 muscarinic acetylcholine receptors, alter lymphatic endothelial cell integrity, and trigger constriction of lymphatic vessels. These metabolites added to cultures also reduce microfilarial production in B. malayi and egg-laying in Caenorhabditis elegans, implying a role in regulating nematode reproduction. Their production is potently inhibited by ethacrynic acid, an existing FDA-approved drug. Our findings reveal a previously unexplored role for filarial-derived cholinergic signaling in parasite reproduction that impacts host lymphatic homeostasis. This work offers insights into the biochemical adaptations that function in the worm life cycle and reveals potential metabolic vulnerabilities in filarial worms.

Authors: Alexandra Grote, Lia Ficaro, Joseph Koussa, Rita A. Boateng, Daniela Chow, Johannes Morstein, Morgan E. Brisse, Jennifer Goldstein, Hongyu Wu, Yen-Chih Chen, Matthew Chung, Christopher Mederos, Niels Ringstad, Eric V. Dang, Alexander Aksenov, Heather D. Hickman, Denis Voronin, Dirk Trauner, Drew R. Jones & Elodie Ghedin

Publisher/Journal: Nature

Article Link: https://www.nature.com/articles/s41467-026-77090-2

Molecules in living systems are not random but are shaped by biological necessity. Mass spectrometry (MS) is a powerful tool for exploring these complex molecular landscapes. Molecular networking links metabolites by spectral similarity, but conventional methods leave many nodes disconnected. We introduce molecular community networking (MCN), which identifies natural molecular clusters and prunes them to keep the strongest links. The approach increases connectivity to about 95% of molecules and better captures structurally related compounds, including distinct ion forms and in-source fragmentation ions. MCN also improves the mapping of molecular space, helping distinguish true novel molecules from artifacts. Using MCN, we discovered dipeptide-conjugated bile acids associated with Bifidobacterium breve and proposed structures for previously unexplored N-acyl amides that interact with G protein-coupled receptors. We also built a global metabolome map from public GNPS/MassIVE data, covering about 8.4 million molecular features, creating a “roadmap” for molecular diversity.

 

Authors: Elizabeth A. Coler, Alexey Melnik, Ali Lotfi, Dana Moradi, Ben Ahiadu, Paulo Wender Portal Gomes, Abubaker Patan, Vincent Charron-Lamoureux, Pieter C. Dorrestein, Stephen Barnes, Vladimir Boginski, Alexander Semenov, Alexander A. Aksenov

Publisher/Journal: Cell Reports Method

Article Link: https://www.cell.com/cell-reports-methods/fulltext/S2667-2375(26)00168-2

 

The microbiome is increasingly recognized as a key factor in health. Intestinal microbiota modulates gut homeostasis via a range of diverse metabolites. In particular, molecules such as short-chain fatty acids (SCFAs), the microbial fermentation products of dietary fiber, have been established to be reflective of microbiome and/or dietary shifts, and SCFAs alterations have been linked to multiple gastrointestinal disorders, from cancer to colitis. Despite their potential as biomarkers, technical challenges in stool collection have limited clinical translation. Here, we present Stool Wipe (S’Wipe), an ultra-low-cost fecal collection method using lint-free, mass spectrometry (MS)-compatible cellulose wipes as toilet paper. Specimens are preserved in ethanol without refrigeration and can be shipped via regular mail. Mass spectrometry analysis demonstrated that S’Wipe captures both volatile and non-volatile metabolites with reproducibility and stability validated for diagnostically relevant molecules. We show that S’Wipe performs equivalently to direct stool collection, enabling interchangeable use and comparison with existing studies. This methodology is ideally suited for large-scale population studies, longitudinal tracking, and personalized medicine applications.

Authors: Dana Moradi, Ali Lotfi, Alexey V Melnik, Aleksandr Smirnov, Konstantin Pobozhev, Hannah Monahan, Evguenia Kopylova, Yanjiao Zhou, Alexander A Aksenov

Publisher/Journal: American Society for Microbiology — mSystems

Article Link: https://journals.asm.org/doi/full/10.1128/msystems.01459-25