Resilience of human gut microbiomes in autism spectrum disorder: measured using stiffness network analysis

ABSTRACT Autism spectrum disorder (ASD) affects an estimated 1%–2% of children worldwide, but its specific etiology remains unclear. In recent years, the gut microbiome’s role in ASD pathogenesis has garnered increasing attention. However, the exact relationship between microbiota and ASD—such as which microbial species significantly impact disease onset and progression—remains unresolved, and effective methods to measure microbial interactions are still lacking. In this study, we introduce an innovative stiffness network analysis (SNA) method to quantify changes in microbial network structure and identify disease-specific microbial bacteria theoretically. The SNA method was applied to reanalyze eight ASD gut microbiome data sets, encompassing 898 ASD samples and 467 healthy control (HC) samples from 16S-rRNA sequencing data. Key findings include the following: (i) an “allies” biomarker subgroup consisting of Bacteroides plebeius , Sutterella , Lachnospira , and Prevotella copri was identified; (ii) a profile monitoring score of 0.72 for the biomarker subgroup, indicating significant relationship changes between HC and ASD states, and (iii) a P/N ratio of biomarker subgroup in ASD-associated gut bacteria that was three times higher than that of HC microbiomes. Additionally, we discuss the non-monotonic relationship alterations within microbial sub-communities in the ASD gut microbiome. IMPORTANCE It is crucial to assess alterations in network structure in different biological states in order to promote health. The stiffness network allows for the exploration of species interactions and the measurement of resilience in complex microbial networks. The objective of this study was to develop a stiffness network analysis (SNA) method for evaluating the contribution of microbial bacteria in differentiating disease samples from healthy control samples by examining changes in network stiffness parameters. Furthermore, the SNA method was employed on both simulated and real autism spectrum disorder gut microbiome data sets to identify potential microbial biomarker subgroups, with a particular focus on the relationship alterations within microbial networks.