ILA Levels Define Divergent Gut Microbiome Networks and Metabolic Profiles

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ILA Levels Define Divergent Gut Microbiome Networks and Metabolic Profiles

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Co-author 1

Paik Seong Lim jamespslim@gmail.com Tungs’ Taichung MetroHarbor Hospital Division of Renal Medicine Taichung Taiwan * National Chung Hsing University Institute of Biomedical Science, College of Life Science Taichung Taiwan

Co-author 2

Ming Ying Wu ying5430@yahoo.com.tw Tungs’ Taichung MetroHarbor Hospital Division of Renal Medicine, Taichung Taiwan -

Co-author 3

Li Shu Chiu t0408@@ms3.sltung.com.tw Tungs’ Taichung MetroHarbor Hospital Division of Renal Medicine, Taichung Taiwan -

Co-author 4

Chi Ta Hsieh t13766@ms3.sltung.com.tw Tungs’ Taichung MetroHarbor Hospital Division of Renal Medicine, Taichung Taiwan -

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Introduction

Indole-3-lactic acid (ILA), a tryptophan-derived metabolite, is increasingly recognized as a marker of gut microbial homeostasis. However, its ecological and functional microbial correlates remain poorly defined.

Methods

We stratified samples into low vs. high ILA groups and analyzed gut microbiota composition, co-occurrence networks, correlation structures, and predicted microbial functions (PICRUSt2). LEfSe was applied to identify discriminant functional biomarkers.

Results

Low ILA was associated with expansion of Escherichia/Shigella and Klebsiella species, reduced network connectivity, and antagonistic ecological structure dominated by Proteobacteria. High ILA corresponded to enriched Clostridium and Bacteroides taxa, cooperative network structure, and balanced phylum-level correlations. Functional predictions showed enrichment of SCFA fermentation pathways in high ILA, whereas low ILA was enriched for stress response and nutrient scavenging functions. LEfSe analysis identified multiple COG, EC, KO, and MetaCyc biomarkers discriminating low ILA states, indicating a functionally simplified but opportunistic metabolic profile.

Conclusion

ILA levels stratify gut microbial communities into ecologically and functionally distinct states. High ILA reflects a stable, fermentative, commensal-dominated ecosystem, whereas low ILA is linked to network collapse and pathobiont-driven metabolism. ILA may thus serve as a marker and potential modulator of microbiome stability.

Kewords