Dataset Information

N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

ABSTRACT:

Background

Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.

Methods and results

Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress.

Conclusions

In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.

SUBMITTER: Pusceddu MM

PROVIDER: S-EPMC4591340 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

Pusceddu Matteo M MM El Aidy Sahar S Crispie Fiona F O'Sullivan Orla O Cotter Paul P Stanton Catherine C Kelly Philip P Cryan John F JF Dinan Timothy G TG

PloS one 20151001 10

<h4>Background</h4>Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFA ...[more]

PMID: 26426902

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Project description:Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that a low dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as a determinant of long-term health, we here study the impact of ELS and dietary PUFAs on the gut microbiota and how this relates to the previously described cognitive, metabolic, and fatty acid profiles. Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 to P9 and to an early diet (P2 to P42) with an either high (15) or low (1) ω-6 linoleic acid to ω-3 alpha-linolenic acid ratio. 16S rRNA was sequenced and analyzed from fecal samples at P21, P42, and P180. Age impacted α- and β-diversity. ELS and diet together predicted variance in microbiota composition and affected the relative abundance of bacterial groups at several taxonomic levels in the short and long term. For example, age increased the abundance of the phyla Bacteroidetes, while it decreased Actinobacteria and Verrucomicrobia; ELS reduced the genera RC9 gut group and Rikenella, and the low ω-6/ω-3 diet reduced the abundance of the Firmicutes Erysipelotrichia. At P42, species abundance correlated with body fat mass and circulating leptin (e.g., Bacteroidetes and Proteobacteria taxa) and fatty acid profiles (e.g., Firmicutes taxa). This study gives novel insights into the impact of age, ELS, and dietary PUFAs on microbiota composition, providing potential targets for noninvasive (nutritional) modulation of ELS-induced deficits. IMPORTANCE Early-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders; however, the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as a determinant of long-term health and as a potential target for noninvasive nutritional strategies to protect against the negative impact of ELS. Here, we give novel insights into the complex interaction between ELS, early dietary ω-3 availability, and the gut microbiota across ages and provide new potential targets for (nutritional) modulation of the long-term effects of the early-life environment via the microbiota.

Project description:ObjectiveTo examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association.Research design and methodsWe evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota.ResultsOver 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P < 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes.ConclusionsRelative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.

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Dataset Information

N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

Background

Methods and results

Conclusions

Publications

N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

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