Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism
Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without anti...
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| Veröffentlicht in: | Molecular psychiatry 2018-12, Vol.23 (12), p.2287-2301 |
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| creator | Soto, Marion Herzog, Clémence Pacheco, Julian A. Fujisaka, Shiho Bullock, Kevin Clish, Clary B. Kahn, C. Ronald |
| description | Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors. |
| doi_str_mv | 10.1038/s41380-018-0086-5 |
| format | Article |
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Ronald</creator><creatorcontrib>Soto, Marion ; Herzog, Clémence ; Pacheco, Julian A. ; Fujisaka, Shiho ; Bullock, Kevin ; Clish, Clary B. ; Kahn, C. Ronald</creatorcontrib><description>Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-018-0086-5</identifier><identifier>PMID: 29910467</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/58 ; 38/77 ; 631/378 ; 631/443 ; 631/45 ; 82/80 ; 96 ; Amygdala ; Animals ; Anti-Bacterial Agents ; Antibacterial agents ; Antibiotics ; Antiprotozoan agents ; Anxiety ; Behavioral Sciences ; Biological Psychology ; Brain ; Brain - metabolism ; Brain-derived neurotrophic factor ; Complications and side effects ; Depression (Mood disorder) ; Diabetes mellitus ; Diabetes therapy ; Diet, High-Fat ; GABA ; Gastrointestinal Microbiome - genetics ; Gastrointestinal Microbiome - physiology ; Germfree ; Glucose ; Health aspects ; Immediate Communication ; Inflammation ; Inflammation - metabolism ; Insulin ; Insulin - metabolism ; Insulin resistance ; Insulin Resistance - physiology ; Intestinal microflora ; Laboratory rats ; Male ; Medicine ; Medicine & Public Health ; Mental depression ; Metabolism ; Metabolites ; Metronidazole ; Metronidazole - pharmacology ; Mice ; Mice, Inbred C57BL ; Microbiomes ; Microbiota ; Microbiota (Symbiotic organisms) ; Neurosciences ; Nucleus accumbens ; Obesity ; Obesity - metabolism ; Obesity - microbiology ; Pharmacotherapy ; Psychiatry ; Psychological aspects ; Risk factors ; RNA, Ribosomal, 16S - drug effects ; RNA, Ribosomal, 16S - genetics ; Tryptophan ; Vancomycin ; Vancomycin - pharmacology ; γ-Aminobutyric acid</subject><ispartof>Molecular psychiatry, 2018-12, Vol.23 (12), p.2287-2301</ispartof><rights>The Author(s) 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>2018. 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Ronald</creatorcontrib><title>Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. 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This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29910467</pmid><doi>10.1038/s41380-018-0086-5</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 101/58 38/77 631/378 631/443 631/45 82/80 96 Amygdala Animals Anti-Bacterial Agents Antibacterial agents Antibiotics Antiprotozoan agents Anxiety Behavioral Sciences Biological Psychology Brain Brain - metabolism Brain-derived neurotrophic factor Complications and side effects Depression (Mood disorder) Diabetes mellitus Diabetes therapy Diet, High-Fat GABA Gastrointestinal Microbiome - genetics Gastrointestinal Microbiome - physiology Germfree Glucose Health aspects Immediate Communication Inflammation Inflammation - metabolism Insulin Insulin - metabolism Insulin resistance Insulin Resistance - physiology Intestinal microflora Laboratory rats Male Medicine Medicine & Public Health Mental depression Metabolism Metabolites Metronidazole Metronidazole - pharmacology Mice Mice, Inbred C57BL Microbiomes Microbiota Microbiota (Symbiotic organisms) Neurosciences Nucleus accumbens Obesity Obesity - metabolism Obesity - microbiology Pharmacotherapy Psychiatry Psychological aspects Risk factors RNA, Ribosomal, 16S - drug effects RNA, Ribosomal, 16S - genetics Tryptophan Vancomycin Vancomycin - pharmacology γ-Aminobutyric acid |
| title | Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism |
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