Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD.
View Article and Find Full Text PDFholds promise as a chassis for producing and secreting heterologous proteins. Used for thousands of years to ferment milk, this species has generally recognized as safe (GRAS) status in the USA and qualified presumption of safety (QPS) status in Europe. In addition, it can be easily genetically modified thanks to its natural competence, and it secretes very few endogenous proteins, which means less downstream processing is needed to purify target proteins, reducing costs.
View Article and Find Full Text PDFThe gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated.
View Article and Find Full Text PDFPrevious studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones.
View Article and Find Full Text PDFHuman microbiomes, particularly in the gut, could have a major impact on the efficacy and toxicity of drugs. However, gut microbial metabolism is often neglected in the drug discovery and development process. Medicen, a Paris-based human health innovation cluster, has gathered more than 30 international leading experts from pharma, academia, biotech, clinical research organizations, and regulatory science to develop proposals to facilitate the integration of microbiome science into drug discovery and development.
View Article and Find Full Text PDFThe effect of the microbiota-gut-brain axis on cognitive development in infancy is increasingly being scrutinized. In this issue of Cell Host & Microbe, Cerdó, Ruiz, and colleagues skillfully combine clinical and preclinical analyses, including a fecal transplantation experiment, to reveal associations between microbiota composition, cognitive scores, and histidine metabolism.
View Article and Find Full Text PDFThe effect of supplementation with strains to prevent the consequences of chronic stress on anxiety in mouse strains sensitive to stress and the consequences on gut microbiota have been relatively unexplored. Thus, we administered a LA205 and LA903 mix to male BALB/cByJrj mice two weeks before and during 21-day chronic restraint stress (CRS) (non-stressed/solvent (NS-PBS), non-stressed/probiotics (NS-Probio), CRS/solvent (S-PBS), CRS/probiotics (S-Probio)). CRS resulted in lower body weight and coat state alteration, which were attenuated by the probiotic mix.
View Article and Find Full Text PDFMetagenome analyses of the human microbiome suggest that horizontal gene transfer (HGT) is frequent in these rich and complex microbial communities. However, so far, only a few HGT studies have been conducted . In this work, three different systems mimicking the physiological conditions encountered in the human digestive tract were tested, including (i) the TNO gastro-Intestinal tract Model 1 (TIM-1) system (for the upper part of the intestine), (ii) the ARtificial COLon (ARCOL) system (to mimic the colon), and (iii) a mouse model.
View Article and Find Full Text PDFBacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the development of NEC lesions and confirm the enteropathogenicity of and in NEC. First, we produced and strains impaired in butyrate production by genetically inactivating the gene encoding β-hydroxybutyryl-CoA dehydrogenase that produces end-fermentation metabolites.
View Article and Find Full Text PDFStressed individuals tend to turn to calorie-rich food, also known as 'comfort food' for the temporary relief it provides. The emotional eating drive is highly variable among subjects. Using a rodent model, we explored the plasmatic and neurobiological differences between 'high and low emotional eaters' (HEE and LEE).
View Article and Find Full Text PDFBackground: Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting.
Results: Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity.
μ-opioid receptors (MOPr) play a critical role in social play, reward and pain, in a sex- and age-dependent manner. There is evidence to suggest that sex and age differences in brain MOPr density may be responsible for this variability; however, little is known about the factors driving these differences in cerebral MOPr density. Emerging evidence highlights gut microbiota's critical influence and its bidirectional interaction with the brain on neurodevelopment.
View Article and Find Full Text PDFAutism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging.
View Article and Find Full Text PDFAerobic bacteria are frequent primocolonizers of the human naive intestine. Their generally accepted role is to eliminate oxygen, which would allow colonization by anaerobes that subsequently dominate bacterial gut populations. In this hypothesis-based study, we revisited this dogma experimentally in a germfree mouse model as a mimic of the germfree newborn.
View Article and Find Full Text PDFGut microbiota metabolizes tryptophan into indole, which can influence brain and behavior. Indeed, some oxidized derivatives of indole, formed in the liver, have neuroactive properties, and indole overproduction by the gut microbiota induces an anxio-depressive phenotype in rodents. The aim of this study was to investigate in humans whether there was a relationship between recurrent depressive symptoms and indole production by the gut microbiota.
View Article and Find Full Text PDFThe number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.
View Article and Find Full Text PDFOxytocin (OT) is a developmentally important neuropeptide recognized to play a dominant role in social functioning and stress-related behaviors, in a sex-dependent manner. Nonetheless, the underlining factors driving OT and OT receptor (OTR) early brain development remain unclear. Recent evidence highlight the critical influence of gut microbiota and its bidirectional interaction with the brain on neurodevelopment via the gut microbiota-brain axis.
View Article and Find Full Text PDFA role of the gut microbiota in psychiatric disorders is supported by a growing body of literature. The effects of a probiotic mixture of four bacterial strains were studied in two models of anxiety and depression, naturally stress-sensitive Fischer rats and Long Evans rats subjected to maternal deprivation. Rats chronically received either the probiotic mixture (1.
View Article and Find Full Text PDFAutism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon.
View Article and Find Full Text PDFPurpose: Previous epidemiologic studies have provided some evidence of an inverse association between fruit and vegetables consumption and risk of developing recurrent depressive symptoms. This association could possibly be explained by the role of such dietary factors on the gut microbiota. Especially, indole, a metabolite of tryptophan produced by gut bacteria, may be associated with the development of mood disorders.
View Article and Find Full Text PDFBackground And Aims: The gut microbiota produces metabolites that are an integral part of the metabolome and, as such, of the host physiology. Changes in gut microbiota metabolism could therefore contribute to pathophysiological processes. We showed previously that a chronic and moderate overproduction of indole from tryptophan in male individuals of the highly stress-sensitive F344 rat strain induced anxiety-like and helplessness behaviors.
View Article and Find Full Text PDFSlowing down translation in either the cytosol or the mitochondria is a conserved longevity mechanism. Here, we found a non-interventional natural correlation of mitochondrial and cytosolic ribosomal proteins (RPs) in mouse population genetics, suggesting a translational balance. Inhibiting mitochondrial translation in C.
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