title: Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour.
abstract: OBJECTIVE
  Gut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM.
  
  
  METHODS
  The present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers.
  
  
  RESULTS
  It was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6.
  
  
  CONCLUSIONS
  In conclusion, we hypothesise that imbalances of the microbiota-gut-brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.
authors.affiliation: 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Skovagervej 2,DK-8240 Risskov,Denmark.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Winther
authors.affiliation: 2Section of Experimental Animal Models,Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,University of Copenhagen,Thorvaldsensvej 57,DK-1871 Frederiksberg C,Denmark.
authors.forename: Betina M
authors.initials: BM
authors.lastname: Pyndt Jørgensen
authors.affiliation: 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Skovagervej 2,DK-8240 Risskov,Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Elfving
authors.affiliation: 3Department of Food Science, Faculty of Science,University of Copenhagen,Denmark.
authors.forename: Denis Sandris
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: 2Section of Experimental Animal Models,Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,University of Copenhagen,Thorvaldsensvej 57,DK-1871 Frederiksberg C,Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Kihl
authors.affiliation: 4Medical Department MEA (Endocrinology and Diabetes),Aarhus University Hospital,8000 Aarhus C,Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.affiliation: 2Section of Experimental Animal Models,Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,University of Copenhagen,Thorvaldsensvej 57,DK-1871 Frederiksberg C,Denmark.
authors.forename: Dorte Bratbo
authors.initials: DB
authors.lastname: Sørensen
authors.affiliation: 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Skovagervej 2,DK-8240 Risskov,Denmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000178:diet therapy / Q000209:etiology* / Q000382:microbiology* / Q000523:psychology; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D005951:Glucose Tolerance Test; D006624:Hippocampus / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008274:Magnesium / Q000008:administration & dosage; D008275:Magnesium Deficiency / Q000178:diet therapy / Q000382:microbiology* / Q000523:psychology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D008274:Magnesium
keywords: animal models; behaviour; depression; gut microbiota; magnesium deficiency