Integrated multi-omics analysis reveals gut dysbiosis and altered energy metabolism in Chinese ALS patients.

Overview

1. Department of Laboratory, Hangzhou Geriatric Hospital, Hangzhou, China
2. Department of Laboratory, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China
3. The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
4. Department of Ultrasonography, Hangzhou Geriatric Hospital, Hangzhou, China
5. Department of Ultrasonography, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a complex etiology. Emerging evidence implicates gut microbiota dysbiosis in ALS pathology via the gut-brain axis, yet the specific integrative profile of the gut microbiome, virome, and metabolome, particularly in Chinese patients, remains incompletely characterized. Although global diversity indices showed no significant differences, taxonomic analysis revealed distinct compositional shifts. The ALS microbiome was characterized by a significant depletion of beneficial anti-inflammatory genera, specifically Akkermansia and Faecalibacterium, and an expansion of opportunistic pathogens such as Escherichia and oral-associated taxa (e.g., Streptococcus). We also observed a specific alteration in the gut virome, with viral genera including Puppervirus and Donellivirus enriched in ALS patients. Functionally, the ALS microbiome exhibited a marked upregulation of pathways involved in L-ascorbate (vitamin C) degradation and fatty acid biosynthesis, suggesting a microbial contribution to systemic oxidative stress. Metabolomic analysis corroborated these findings, identifying 271 differentially expressed metabolites. ALS patients showed elevated levels of inflammatory lipids (e.g., LysoPC) and metabolic intermediates of the tricarboxylic acid (TCA) cycle, alongside a downregulation of antioxidants. Integrative analysis highlighted profound dysregulation in porphyrin metabolism, oxidative phosphorylation, and energy homeostasis. Our findings demonstrate that ALS is associated with a specific dysbiotic gut ecosystem characterized by the loss of protective commensals, unique viral signatures, and functional metabolic reprogramming that exacerbates host oxidative stress and energy deficits. These results provide new insights into gut-brain interactions and highlight microbial antioxidant depletion as a potential therapeutic target.

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a devastating disease with no cure. While gut bacteria are known to influence brain health, we still do not understand exactly how they contribute to ALS progression. In this study, we used advanced DNA sequencing and chemical analysis to deeply examine the gut ecosystem of ALS patients. Beyond just cataloging which bacteria are present, we discovered what they are doing: the ALS microbiome actively breaks down vitamin C (a critical antioxidant) and disrupts energy metabolism. We also found a loss of protective bacteria that maintain the gut barrier. These findings are significant because they suggest that the gut microbiome in ALS patients may be actively fueling the disease by depleting the body’s antioxidant reserves. This points to a new potential treatment strategy: targeting these specific bacterial functions or replenishing specific metabolites to protect motor neurons.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• bioproject:PRJNA1395841, at NCBI BioProject; found in “DATA AVAILABILITY”

Data availability

The sample and sequence data obtained in this study have been submitted to the NCBI BioSample and Sequence Read Archive (SRA) under BioProject accession number PRJNA1395841 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1395841).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 17 MeSH terms, 44 references.

Cite

This paper

Ma, X., Jiang, Z., Yang, T., Zhang, H., Lu, W., Liu, K., Fan, X., Yang, G., & Wu, S. (2026). Integrated multi-omics analysis reveals gut dysbiosis and altered energy metabolism in Chinese ALS patients. Microbiology spectrum, 14(6), e00609-26. https://doi.org/10.1128/spectrum.00609-26

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