The gut microbiota influences blood-brain barrier permeability in mice

By V. Braniste, Maha Al-Asmakh, C. Kowal, F. Anuar, Afrouz Abbaspour, Miklós Tóth, Agata Korecka, N. Bakočević, Lai Guan Ng, Parag Kundu and 8 more. Science Translational Medicine, 2014

2,211 citations recorded by the source corpus.

The intestinal microbiota helps to maintain the integrity of the blood-brain barrier in fetal and adult mice. The Gut Microbiota and the Blood-Brain Barrier The blood-brain barrier is an important gateway that controls the passage of molecules and nutrients in and out of the brain. An intact blood-brain barrier is a crucial checkpoint for appropriate development and function of the brain. Braniste et al. now show that germ-free pregnant dams, devoid of maternal microbes, have offspring that show increased permeability of the blood-brain barrier. This elevated permeability was also observed in adult germ-free mice. However, fecal transplants from mice exposed to bacteria into adult germ-free mice reduced blood-brain barrier permeability, possibly through the regulation of tight junction proteins. These findings suggest that crosstalk between the gut microbiota and the brain, initiated during the intrauterine period, is perpetuated throughout life. Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota–BBB communication is initiated during gestation and propagated throughout life.

Subfields: Molecular Biology, Neurology, Oncology

View Paper: https://www.semanticscholar.org/paper/86a46ab08bb7d18aa6b594317814fe4903d50c81

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Citations in the corpus

The blood–brain barrier in systemic infection and inflammation (2021, background): “Since it was first noticed that germ-free mice have a leakier BBB than mice with an intact microbiome, investigations have shown that short‐chain fatty acids such as butyrate induce tight junction formation at the BBB [159].”
Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017, background): “Because the lethal irradiation used in transplantation experiments causes leakage in the BBB, it is unclear whether the myeloid cells responsible are brain-resident microglia, bone marrow–derived monocytes that engraft into the brains of recipient mice, or both.”
Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis (2019, background): “levels of butyrate, or by the administration of bacterial fermentation products to GF mice [104].”
The Host Shapes the Gut Microbiota via Fecal microRNA (2016, positive): “Cell H din-1, Claudin-1, Claudin-2, and Claudin-5) that were demonstrated to be regulated by symbiotic bacteria (Braniste et al., 2014).”
The Controversial Role of Human Gut Lachnospiraceae (2020, background): “Upregulate tight junction and proteins claudin-5 and restore the blood-brain barrier permeability [76].”
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “Comparatively, gut to CNS signaling has been studied for a short period, and Abbreviations: Aβ, amyloid-β peptide; AD, Alzheimer’s disease; ASD, autism spectrum disorder; αSyn, α-synuclein; BBB, blood-brain barrier; BDNF, brainderived neurotrophic factor; BHB, β-hydroxybutyrate; CNS, central nervous”
Short-chain fatty acids: linking diet, the microbiome and immunity (2024, positive): “Interestingly, germ-free mice have increased BBB permeability, and this can be reversed by colonization of the intestine with butyrogenic bacteria, which induce an increased expression of occludin 142 .”
The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology (2020, background): “Importantly, the BBB protects the brain from pathogens and unwanted immune reactions that could damage the neurons and their connections (34).”
The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “This could not be achieved by administration Bacteroides thetaiotaomicron, producing mainly acetate and propionate, suggesting that indeed fermentation-derived butyrate supported BBB permeability (Braniste et al., 2014).”
Kynurenine pathway metabolism and the microbiota‐gut‐brain axis (2017, background): “However, the integrity of the BBB may be contingent on the gut microbiota (Braniste et al., 2014) such that the brain appears more accessible in GF animals.”
Control of Brain Development, Function, and Behavior by the Microbiome (2015, positive): “Intriguingly, GF mice have significantly increased permeability of the BBB, both during fetal development and in adulthood (Braniste et al., 2014) (Figure 2).”