Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.
Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and identified enrichment in functional KEGG pathway terms relevant to processes such as the biosynthesis of unsaturated fatty acids and antioxidant metabolism. These results indicate that DHA alters commensal community composition and produces beneficial effects on anxiety and depressive-like behaviors in a sex-specific manner. The present study provides insight into the mechanistic role that gut microbes may play in the regulation of anxiety and depressive-like behaviors and how dietary intervention can modulate these effects.
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, United States. Electronic address: davisdaniel@missouri.edu.
Daniel J
DJ
Davis
Interdisciplinary Neuroscience Program, University of Missouri-Columbia, Columbia, MO 65211, United States.
Patrick M
PM
Hecht
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Eldin
E
Jasarevic
Interdisciplinary Neuroscience Program, University of Missouri-Columbia, Columbia, MO 65211, United States; Department of Psychological Sciences, University of Missouri-Columbia, Columbia, MO 65211, United States; Department of Radiology, University of Missouri-Columbia, Columbia, MO 65212, United States; Department of Neurology, University of Missouri-Columbia, Columbia, MO 65212, United States; Thompson Center for Autism and Neurodevelopmental Disorders, William and Nancy Thompson Endowed Chair in Radiology, University of Missouri-Columbia, Columbia, MO 65212, United States.
David Q
DQ
Beversdorf
Interdisciplinary Neuroscience Program, University of Missouri-Columbia, Columbia, MO 65211, United States; Department of Psychological Sciences, University of Missouri-Columbia, Columbia, MO 65211, United States; Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, United States.
Matthew J
MJ
Will
Division of Animal Sciences, University of Missouri-Columbia, Columbia, MO 65211, United States; Department of Nutrition and Exercise Physiology, University of Missouri-Columbia, Columbia, MO 65211, United States.
Kevin
K
Fritsche
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, United States.
Catherine H
CH
Gillespie
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000523:psychology; D004032:Diet; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005243:Feces / Q000737:chemistry; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D000069196:Gastrointestinal Microbiome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D012727:Sex Characteristics; D012934:Social Isolation
D004281:Docosahexaenoic Acids
Anxiety; Depression; Docosahexaenoic acid; Microbiome; Sex difference