# Profiling of the mycobiome and metabolome: a comparative study of benign pulmonary nodules and lung adenocarcinoma

## TL;DR

This study identifies fungal and metabolite biomarkers to distinguish benign lung nodules from lung cancer and explores their interactions.

## Contribution

A novel multi-omics network linking gut fungi, metabolites, and cytokines in lung adenocarcinoma differentiation.

## Key findings

- Gut fungal communities differ significantly between benign and cancerous lung nodules.
- Specific metabolites like DPAn-6 and IPA are elevated in lung adenocarcinoma patients.
- An integrated model combining fungi and metabolites effectively differentiates benign from malignant nodules.

## Abstract

Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer, is a form of malignant pulmonary nodule that requires clinical differentiation from benign pulmonary nodules (BPN). The mechanisms underlying the development of LUAD are complex, and effective non-invasive methods for differentiating BPN from LUAD are lacking. This study aimed not only to distinguish BPN from LUAD using gut fungi and serum metabolites, but also to establish an integrated network of gut fungi–metabolite–cytokine interactions.

Fecal and serum samples from individuals with BPN and patients with LUAD were subjected to internal transcribed spacer sequencing, ultra-performance liquid chromatography–tandem mass spectrometry, and multiplex Luminex assays to quantify gut fungi, metabolites, and cytokines, respectively.

A significant difference in gut fungal communities was observed between the BPN and LUAD groups. Multiple genera and species were more abundant in LUAD than in BPN. Docosapentaenoic acid n-6 (DPAn-6), indole-3-propionic acid (IPA), and interferon-γ-induced protein 10 (IP-10) were significantly elevated in the LUAD group. The integrated model established using a combination of gut fungi and metabolites demonstrated excellent performance in distinguishing BPN from LUAD. A network of interactions was established among differentially abundant gut fungi, serum metabolites, and cytokines.

Our study identifies a novel panel of fungal and metabolite biomarkers for differentiating between BPN and LUAD, and constructs a multi-omics network that provides new insights into investigating the mechanistic role of gut mycobiota dysbiosis in LUAD.