Acetate supplementation rescues social deficits and alters transcriptional regulation in prefrontal cortex of Shank3 deficient mice

Osman, Aya; Mervosh, Nicholas L.; Strat, Ana N.; Euston, Tanner J.; Zipursky, Gillian; Pollak, Rebecca M.; Meckel, Katherine R.; Tyler, Scott R.; Chan, Kenny L.; Buxbaum Grice, Ariela; Drapeau, Elodie; Litichevskiy, Lev; Gill, Jasleen; Zeldin, Sharon M.; Thaiss, Christoph A.; Buxbaum, Joseph.D.; Breen, Michael S.; Kiraly, Drew D.

doi:10.1016/j.bbi.2023.08.020

Cited by 3 publications

(1 citation statement)

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“…Interestingly, increased valeric acid and decreased acetic acid concentrations have been measured in fecal samples from children with autism [45], suggesting a connection between the regulation of these metabolites and neurodevelopmental disorders. Acetate supplementation has also rescued social deficits in an autistic mouse model, implicating decreased central acetic acid levels with impaired social interaction in BD mice [46].…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation from individual with bipolar disorder and healthy control elicits distinct behaviors and metabolite profiles in mice

Bukowski-Thall,

Fellendorf,

Gorkiewicz

et al. 2023

Preprint

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Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes of depression and (hypo-) mania. The gut microbiome is a potential avenue through which metabolic signaling, inflammatory pathways, environmental factors, and genetics influence BD pathogenesis via the gut-brain axis. Fecal microbiota transplantation (FMT) is a powerful translational tool for investigating the connections between the gut microbiome and BD, and there is evidence FMT can transfer affective symptoms of BD from humans to mice. In this study, we compared the behavior, gut-brain metabolomic profiles, and inflammatory marker expression in two groups of adult female C57BL/6J mice, one receiving FMT from a human donor with BD in a mixed episode ( HAM-D = 20, YMRS = 14) and another receiving FMT from a mentally healthy weight and age-matched control donor without BD (HAM-D and YMRS = 0). Here, we demonstrate that mice receiving FMT from individuals with BD had an increased abundance of Bacteroidota and decreased abundances ofParabacteroides merdaeandAkkermansia muciniphilaassociated with altered levels of fecal metabolites, short-chain fatty acids, and related gut hormone expression relative to mice receiving control donor FMT. BD mice also exhibited differential regulation of several metabolites and inflammatory markers in the amygdala, with glycine being the most prominently affected. Furthermore, BD mice displayed increased anxiety-like behavior and decreased sociability, indicating that aspects of the behavioral phenotype of BD are transferable from humans to mice via FMT. Taken together, these findings implicate gut-brain signaling in the physiological and behavioral changes observed in our BD-FMT mouse model.

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Section: Discussionmentioning

confidence: 99%