Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring

By Shelly A Buffington, Gonzalo Viana Di Prisco, T. Auchtung, N. Ajami, J. Petrosino, Mauro Costa-Mattioli. Cell, 2016

1,069 citations recorded by the source corpus.

SUMMARY Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here we report that maternal high fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity and behavior, and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders.

Subfields: Molecular Biology, Pharmacy, Social Psychology

View Paper: https://www.semanticscholar.org/paper/56b7b88fbdb2a4793fa2e99a49f8aa59d5b0279e

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Citations in the corpus

The Central Nervous System and the Gut Microbiome (2016, background): “The social deficit in these mice could be reversed by administration of Lactobacillus reuteri, found to be missing in the gut microbiome of high-fat-diet offspring (Buffington et al., 2016).”
Microbiota in health and diseases (2022, background): “Moreover, Buffington et al.62 reported that maternal high-fat diet induces gut microbiota shifts and physiological change in the offspring brain, such as fewer oxytocin immunoreactive neurons in the hypothalamus.”
The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology (2020, background): “In details, compared to colonized mice, GF mice showed exaggerated hypothalamic–pituitary–adrenal (HPA) restrain stress reaction (10), impared social behaviors (12, 15, 82), reduced anxiety-like behavior (7, 81–83) and increased motor and rearing activity (80, 84).”
Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration (2017, background): “These findings of social deficits in germ-free mice have recently been replicated (Buffington et al. 2016) but opposite findings have also been reported (Arentsen et al. 2015).”
Role of Lactobacillus reuteri in Human Health and Diseases (2018, background): “This regulatory function of L. reuteri was attributed to its capability to increase the level of oxytocin (Poutahidis et al., 2013a; Buffington et al., 2016).”
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “In a similar way, growing evidence has shown that alterations in maternal microbiome during pregnancy, such as use of antibiotics or probiotics (41, 42), variations in diet (43), immune activation (44, 45), and exposure to stress (46) can modulate the microbiome, neurodevelopment, and behavior of of”
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019, neutral): “, 2011), as well as in mouse models of ASD (Buffington et al., 2016; Coretti et al., 2017; Hsiao et al., 2013; Kim et al., 2017; Liu et al., 2018; de Theije et al., 2014).”
The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Conversely, an abundance of a mucin-degrading gut bacteria, Akkermansia muciniphila, is associated with increased metabolic health in obese patients (Dao et al., 2016) and in mice fed a HFD (Schneeberger et al., 2015).”
Mechanisms underlying microbial-mediated changes in social behavior in mouse models of Autism Spectrum Disorder (2018, positive): “As previously described, unlike conventionally colonized mice, GF mice displayed social deficits (Buffington et al., 2016; Desbonnet et al., 2014).”
Mechanisms of Action of Probiotics. (2019, background): “reuteri failed to mitigate anxiety but was able to restore oxytocin concentrations, the mesolimbic dopamine reward system, and social behaviors in the offspring that were fed a high-fat maternal diet (157).”
The gut microbiota mediates the anti-seizure effects of the ketogenic diet (2018, neutral): “Several diet-induced host pathologies are mediated by changes in the gut microbiota in mouse models, including symptoms of atherosclerosis in response to the carnitine-rich diet, undernutrition in response to the Malawian diet, and abnormal social behavior in response to maternal high-fat diet (Buff”
Factors affecting the composition of the gut microbiota, and its modulation (2019, background): “, 2015), and affecting the behavioral and neurological functions of the host (Buffington et al., 2016; Wahlström et al., 2016; Zheng et al., 2019).”