Targeted fecal microbiota transplantation ameliorates autism-like behaviors via gut-brain axis and excitatory/inhibitory balance restoration in a propionic acid mouse model.

Scientists gave mice with autism-like behaviors a treatment called fecal microbiota transplantation (FMT) - transferring healthy gut bacteria from carefully chosen human donors. The treatment improved the mice's social behavior and reduced repetitive actions. It worked by restoring healthy gut bacteria and fixing chemical imbalances in the brain. The study suggests gut health might be connected to autism symptoms, but more research in humans is needed.

This preclinical study investigated targeted fecal microbiota transplantation (FMT) as a treatment for autism-like behaviors in a propionic acid-induced mouse model. Researchers selected human donors with high Lactobacillus levels and found that FMT from these donors improved social interaction deficits and reduced repetitive behaviors in mice. The intervention restored gut microbiota diversity, normalized neurotransmitter balance (glutamate/GABA ratio) in the prefrontal cortex, and corrected excitatory/inhibitory imbalances in brain neurons. The study demonstrates the gut-brain axis connection in autism and suggests that careful donor selection based on microbiota composition may enhance FMT effectiveness.

While promising, these findings require human clinical trials for validation.

Provides preliminary evidence that targeted FMT with careful donor selection may be a potential therapeutic approach for autism. The gut-brain axis mechanism suggests microbiome-based interventions warrant investigation. However, human clinical trials are essential before considering clinical application, particularly given safety considerations with FMT procedures.

This is an animal study using a propionic acid-induced autism model, which may not fully represent human autism spectrum disorder. Sample size not reported. Human clinical trials are needed to validate these preclinical findings and assess safety and efficacy in autistic individuals.

Autism spectrum disorder (ASD) is characterized by social interaction deficits, repetitive behaviors, and restricted interests. Emerging evidence suggests a role for the gut microbiota in ASD pathophysiology, with fecal microbiota transplantation (FMT) emerging as a potential therapeutic strategy. This study investigated the effects of targeted FMT using processed fecal suspensions from rigorously screened healthy human donors, selected by 16S rRNA sequencing for high Lactobacillus abundance, on a propionic acid (PPA)-induced ASD mouse model. PPA-exposed mice exhibited ASD-like behaviors, including anxiety, repetitive grooming, and social interaction deficits, along with alterations in gut microbiota composition, SCFA levels, and neurotransmitter profiles.

Donor selection based on 16S rRNA gene sequencing revealed that FMT from donors with high Lactobacillus abundance was more effective in improving social interaction deficits compared to donors with lower Lactobacillus levels. Targeted FMT intervention restored gut microbiota diversity and enriched beneficial taxa, such as Lactobacillus, Roseburia, and Blautia. Furthermore, targeted FMT reduced PPA levels in both feces and the prefrontal cortex (PFC), and normalized the Glu/GABA ratio in the PFC, suggesting a restoration of E/I balance. Electrophysiological recordings confirmed that FMT corrected the E/I imbalance in PFC pyramidal neurons by reducing sEPSC frequency and increasing sIPSC frequency.

These findings demonstrate that FMT can ameliorate ASD-like behaviors in a PPA-induced mouse model by modulating gut microbiota and restoring E/I balance in the brain. Our study provides foundational evidence for the potential of targeted FMT as a therapeutic strategy for ASD, highlighting the importance of donor selection based on gut microbiota composition.