Abstract

Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.

Highlights

  • In our recent publication [34], we illustrated that rats treated with PPA showed impaired social behavior exhibited by reduced time spent in the social chamber and time interacting with the social stimulus compared to normal saline (NS) control group

  • Microbiota Diversity Is Enriched upon BF and fecal microbiota transplantation (FT) Treatments

  • We evaluated the diversity of fecal microbiota between different groups through analyzing the V3–V4 hypervariable region of the 16S rRNA gene using next-generation sequencing

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Summary

Introduction

Autism spectrum disorders (ASD) are a group of conditions categorized by a variety of neurodevelopmental and behavioral malfunctions that have come to form archetypal features related to the disorder [1]. Changes in the gastrointestinal microbiota composition with links to the neuroimmune-gut brain axis are considered characteristic of people with autism [4]. Recent studies have suggested a relationship between gut microbiota and the commencement of emotional and behavioural traits indicating a relatively strong gut-brain axis link [5]. Anxiety and ASD were all associated with different patterns of variations in microbiota, indicating a link between these diseases and gut bacteria [6]. Gut microbiota has been associated with a range of neuro-related diseases, i.e., neuromyelitis optica, Guillain-Barré syndrome (GBS), and multiple sclerosis. Neuromyelitis patients had antibodies that cross react with Clostridium perfringens proteins [8] and cross reactivity between antibodies against campylobacter jejuni, the common cause agents for human enteritis, and the neural surface antigens is understood to be a key the risk factor for GBS [9]

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