Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

Abstract

Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut–brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.

Leaky gut biomarkers in casein- and gluten-rich diet fed rat model of autism

“…Recent studies suggest potential, but unconfirmed, associations between dietary, metabolic, infective, and GI influences and the behavioral improvements or exacerbations of ASDs. PPA as a metabolic end product of multiple ASD-associated bacteria, such as Desulfovibrio, Clostridia , and Bacteroidetes , is reasonably linked to ASDs and can induce widespread effects on gut, brain, and behavior [ 23 ].…”

“…Most recently, our team tested the application of two interventional treatments, Bifidobacterium probiotic treatment and fecal transplantation as two strategies to treat dysbiosis, and social interaction impairment in oral PPA-administered rats. Both treatments were effective in modulating the overgrowth of gut Clostridium bacteria and social impairment in PPA-rodent model of autism [ 23 ].…”

Maternal Immune Activation Causes Social Behavior Deficits and Hypomyelination in Male Rat Offspring with an Autism-Like Microbiota Profile

“…Compared with children without ASD, multiple microbiota species are elevated or reduced in children with ASD who have complex neurodevelopmental disorders involving disruptions in language and social behavior, restricted interests, and repetitive behaviors [9]. Microbiota transfer therapies have reported an improvement in ASD behavioral symptoms [32,33], suggesting that correcting the altered microbiota profile is a promising treatment strategy for ASD. Among the various changed microbiota species in MIA offspring, we demonstrated that the abundance of Alistipes and Actinobacteria was associated with the profile of social behavior, and Fusobacterium and Coprococcus was associated with the profile of anxietylike and repetitive behavior; this suggests that Alistipes, Actinobacteria, Fusobacterium, and Coprococcus may be microbiome biomarkers or treatment targets for ASD.…”

Neurogenic Inflammation: One of the Participants of Migraine and the Contribution of Translational Research

“…Developing animal models of human illnesses is a challenging task for translational research, but it is indispensable to understanding pathomechanism, searching for biomarkers, and engineering novel treatment [158,159,160,161,162,163,164,165,166]. Migraine research is no exception.…”