Gut Microbiome Ecological Network Destabilization in Amyotrophic Lateral Sclerosis: Insights from In tegrated Oral–Gut Analysis

The pathogenesis of amyotrophic lateral sclerosis (ALS) involves multiple systems, among which the "gut-brain axis" has been extensively studied. However, the characteristics of intestinal microbiota alterations and their potential association with the oral microbiota remain unclear. This cohort study aims to characterize the ecological destabilization of intestinal microbiota in ALS patients. On this basis, this study further explored the potential association between the intestinal and oral microbiotas. In this study, paired oral and fecal samples from ALS patients and fecal samples from healthy controls were collected and subjected to 16S rRNA amplicon sequencing. The results showed that the intestinal microbiota in ALS patients exhibited significant compositional shifts, characterized by enrichment of pro-inflammatory genera and depletion of butyrate-producing genera, along with reduced alpha diversity. Critically, quantitative analysis using a potential landscape model revealed that this altered community was in a metastable state (comprehensive stability index: HC + 0.00110 vs. ALS − 0.0118), indicating ecological destabilization. this study examined oral-gut microbial interactions and identified 20 significant correlations (|r| ≥ 0.6), with the strongest between oral Prevotella salivae and intestinal Dorea (r = 0.937). Notably, the intestinal genera involved in these associations ( Dorea , Ruminococcus , and Blautia ) were also differentially abundant in ALS patients, suggesting that oral-gut microbial interactions may contribute to intestinal dysbiosis. This study demonstrates that the intestinal microecosystem in ALS patients exhibits features of ecological destabilization, and identifies oral-gut microbial interactions may as potential drivers of intestinal dysbiosis.