Prevention of diet restriction induced hyperactivity but not body-weight reduction in rats co-treated with tryptophan: relationship with striatal serotonin and dopamine metabolism and serotonin-1A auto-receptor expression.
Nutritional neuroscience
Anorexia Nervosa (AN) is an eating and behavioral disorder characterized with anxiety/depression, hyperactivity, behavioral impulsivity and psychosis. Most of the associated symptoms are related to the deficiency of serotonin (5-hydroxytryptamine: 5-HT) stores. A deficiency of 5-HT can modulate dopamine neurotransmission in the striatum to elicit hyperactivity and psychosis in AN patients. Also, the release and availability of 5-HT are modulated by serotonin-1A (5-HT1A) auto-receptor. The present study investigates the role of striatal metabolism of 5-HT and dopamine in precipitating hyperactivity in the rat model of diet restriction (DR) induced AN. The role of tryptophan (Trp) in influencing the 5-HT metabolism and the mRNA expression of 5-HT1A auto-receptor is also investigated. We find that long-term DR for 38 days reduces body-weight in rats and produces hyperactivity, similar to AN. This hyperactivity is characterized by declined striatal metabolism of both, dopamine and 5-HT. The mRNA expression of 5-HT1A auto-receptor in the raphe nuclei is also decreased. Trp co-treatment improves these deficiencies in monoamine metabolism and alleviates hyperactivity. Interestingly, DR-induced changes in body-weights are not effected by Trp co-treatment. The study suggests that the striatal metabolism of 5-HT and dopamine and mRNA expression of 5-HT1A auto-receptor has an important role in the pathogenesis of AN. The finding suggests that co-use of Trp can prevent precipitation of AN by normalizing 5-HT metabolism.
10.1080/1028415X.2021.1901046
The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.
Chernikova Michelle A,Flores Genesis D,Kilroy Emily,Labus Jennifer S,Mayer Emeran A,Aziz-Zadeh Lisa
Nutrients
Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.
10.3390/nu13124497
Gut commensal alleviates inflammatory arthritis.
Gut
OBJECTIVE:Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA. DESIGN:Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal in RA. The effects of -derived microbial metabolites on the differentiation of CD4 T cells and macrophage polarisation were also investigated. RESULTS:The relative abundance of in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of . CONCLUSIONS: and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.
10.1136/gutjnl-2022-327756
Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.
Cell
Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.
10.1016/j.cell.2013.11.024
Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior.
Zhan Yang,Paolicelli Rosa C,Sforazzini Francesco,Weinhard Laetitia,Bolasco Giulia,Pagani Francesca,Vyssotski Alexei L,Bifone Angelo,Gozzi Alessandro,Ragozzino Davide,Gross Cornelius T
Nature neuroscience
Microglia are phagocytic cells that infiltrate the brain during development and have a role in the elimination of synapses during brain maturation. Changes in microglial morphology and gene expression have been associated with neurodevelopmental disorders. However, it remains unknown whether these changes are a primary cause or a secondary consequence of neuronal deficits. Here we tested whether a primary deficit in microglia was sufficient to induce some autism-related behavioral and functional connectivity deficits. Mice lacking the chemokine receptor Cx3cr1 exhibit a transient reduction of microglia during the early postnatal period and a consequent deficit in synaptic pruning. We show that deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes that have been previously associated with autism and other neurodevelopmental and neuropsychiatric disorders. These findings open the possibility that disruptions in microglia-mediated synaptic pruning could contribute to neurodevelopmental and neuropsychiatric disorders.
10.1038/nn.3641
Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions.
Ristori Maria Vittoria,Quagliariello Andrea,Reddel Sofia,Ianiro Gianluca,Vicari Stefano,Gasbarrini Antonio,Putignani Lorenza
Nutrients
Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are "picky eaters" and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.
10.3390/nu11112812
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice.
Cell
Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
10.1016/j.cell.2019.05.004