The live biotherapeutic Blautia stercoris MRx0006 attenuates social deficits, repetitive behaviour, and anxiety-like behaviour in a mouse model relevant to autism

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential role for the gut microbiome in ASD, and consequently, the microbiota represents a potential target in the development of novel therapeutics for this neurodevelopmental disorder. In this study, we investigate the efficacy of the live biotherapeutic strain, Blautia stercoris MRx0006, in attenuating some of the behavioural deficits in the autism-relevant, genetic mouse model, BTBR T+ Itpr3tf/J (BTBR). We demonstrate that daily oral administration with MRx0006 attenuates social deficits while also decreasing repetitive and anxiety-like behaviour. MRx0006 administration increases the gene expression of oxytocin and its receptor in hypothalamic cells in vitro and increases the expression of hypothalamic arginine vasopressin and oxytocin mRNA in BTBR mice. Additionally at the microbiome level, we observed that MRx0006 administration decreases the abundance of Alistipes putredinis, and modulates the faecal microbial metabolite profile. This alteration in the metabolite profile possibly underlies the observed increase in expression of oxytocin, arginine vasopressin and its receptors, and the consequent improvements in behavioural outcomes. Taken together, these findings suggest that the live biotherapeutic MRx0006 may represent a viable and efficacious treatment option for the management of physiological and behavioural deficits associated with ASD.

Keywords: Autism; BTBR; Gut-brain axis; Live biotherapeutic; Microbiota.