Ganoderma lucidum sporoderm-broken spore powder (GLSP) has been historically documented for its anti-aging and anti-tumor effects. Although several studies have reported that GLSP and related substance may improve physiological function by regulating the gut microbiota, the underlying mechanisms and their effect on intestinal function remains largely unknown. In this study, we comprehensively investigated the impact of dietary GLSP on intestinal epithelial dynamics and barrier function, assessed by single-cell RNA sequencing (scRNA-seq), using murine models spanning physiological homeostasis and DSS-induced intestinal injury. Our study reveals that GLSP protects intestinal epithelia against chemical and age-related barrier injury by promoting the coordinated expansion of stem/progenitor compartments and restoring both the mucus and physical barriers. Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). FMT from GLSP-diet donors successfully recapitulated the protective effects in gut microbiota-depleted recipient mice. Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified the enrichment of SCFA-producing genera, and previously unrecognized microbial metabolites, such as indole-2-carboxylic acid, 3-Methyloxindole, and 4-hydroxyindole. These microbial metabolites are likely to play an essential role in reprogramming the intestinal metabolome, particularly tryptophan–indole metabolic pathways, to mediate intestinal homeostasis. These findings provide novel insights and potential directions for the development of new drugs targeting intestinal injury.

Autism Spectrum Disorder (ASD) is a collective term for neurodevelopmental disorders with core features of social communication impairment, restricted and repetitive behaviors, and narrow interests. These include classic autism, Asperger’s syndrome, and pervasive developmental disorder not otherwise specified. ASD is currently managed with behavioral interventions, rehabilitation training, and family support, but there is no curative medication. Recent studies suggest that some patients with ASD may experience gastrointestinal symptoms. Perhaps this is associated with the disturbances of gut microbiota. Increasing evidence has demonstrated that the composition of gut microbiota in ASD individuals is different from that in normal population and may be associated with neurodevelopmental processes via the gut–brain axis. This article reviews the evidence for the association between gut microbiota and ASD, describes the characteristics of microbial changes, and analyzes the mechanism by which changes in the composition of the microbiota affect the occurrence and development of ASD. Finally, we review recent advances in microbiota-targeted therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation, which provide new approaches to alleviate and improve autism-related symptoms and point out the future research direction.