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

Pusceddu MM, El Aidy S, Crispie F, O'Sullivan O, Cotter P, Stanton C, Kelly P, Cryan JF, Dinan TG - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of maternal separation (MS) and EPA/DHA administration on rat gut microbiota.Relative abundance of significantly altered microbial genera in the MS-saline and EPA/DHA treated groups (A) and NS-saline and EPA/DHA treated groups (B). Median with interquartile ranges is depicted. Significant difference indicated by *, p<0.05; **, p<0.01; ***, p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4591340&req=5

pone.0139721.g004: Effects of maternal separation (MS) and EPA/DHA administration on rat gut microbiota.Relative abundance of significantly altered microbial genera in the MS-saline and EPA/DHA treated groups (A) and NS-saline and EPA/DHA treated groups (B). Median with interquartile ranges is depicted. Significant difference indicated by *, p<0.05; **, p<0.01; ***, p<0.001.

Mentions: Long-term EPA/DHA supplementation has a strong impact on the composition of the gut microbiota in MS rats (Fig 4A). In particular, high dose administration of EPA/DHA was associated with higher levels of the butyrate producing bacteria; Butyrivibrio. Moreover, high dose supplementation of EPA/DHA elevated the levels of several members Actinobacteria (such as Aerococcus), with a concomitant reduction of the abundance of members of Proteobacteria (such as Undibacterium). The results are in agreement with a recent study on maternal prenatal stress, which reported lower quantities of lactic acid bacteria such as Lactobacillus, Lactococcus, Aerococcus and Bifidobacteria and significantly higher relative abundance of Proteobacterial members [17]. Altogether, this pattern of altered gut microbiota in MS rats support the existence of a potentially increased level of inflammation, which could be reversed by long-term supplementation of high dose of n-3 PUFAs. In fact, diets rich in PUFAs have been shown to positively influence immune function [42]. The possible underlying mechanisms by which PUFAs exert their beneficial effects on health were shown to involve the inhibition of pro-inflammatory cytokine synthesis (tumor necrosis factor alpha and interleukin-1), modulation of the hypothalamic-pituitary-adrenal anti-inflammatory responses, and induction of the release of acetylcholine [43].


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

Pusceddu MM, El Aidy S, Crispie F, O'Sullivan O, Cotter P, Stanton C, Kelly P, Cryan JF, Dinan TG - PLoS ONE (2015)

Effects of maternal separation (MS) and EPA/DHA administration on rat gut microbiota.Relative abundance of significantly altered microbial genera in the MS-saline and EPA/DHA treated groups (A) and NS-saline and EPA/DHA treated groups (B). Median with interquartile ranges is depicted. Significant difference indicated by *, p<0.05; **, p<0.01; ***, p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591340&req=5

pone.0139721.g004: Effects of maternal separation (MS) and EPA/DHA administration on rat gut microbiota.Relative abundance of significantly altered microbial genera in the MS-saline and EPA/DHA treated groups (A) and NS-saline and EPA/DHA treated groups (B). Median with interquartile ranges is depicted. Significant difference indicated by *, p<0.05; **, p<0.01; ***, p<0.001.
Mentions: Long-term EPA/DHA supplementation has a strong impact on the composition of the gut microbiota in MS rats (Fig 4A). In particular, high dose administration of EPA/DHA was associated with higher levels of the butyrate producing bacteria; Butyrivibrio. Moreover, high dose supplementation of EPA/DHA elevated the levels of several members Actinobacteria (such as Aerococcus), with a concomitant reduction of the abundance of members of Proteobacteria (such as Undibacterium). The results are in agreement with a recent study on maternal prenatal stress, which reported lower quantities of lactic acid bacteria such as Lactobacillus, Lactococcus, Aerococcus and Bifidobacteria and significantly higher relative abundance of Proteobacterial members [17]. Altogether, this pattern of altered gut microbiota in MS rats support the existence of a potentially increased level of inflammation, which could be reversed by long-term supplementation of high dose of n-3 PUFAs. In fact, diets rich in PUFAs have been shown to positively influence immune function [42]. The possible underlying mechanisms by which PUFAs exert their beneficial effects on health were shown to involve the inhibition of pro-inflammatory cytokine synthesis (tumor necrosis factor alpha and interleukin-1), modulation of the hypothalamic-pituitary-adrenal anti-inflammatory responses, and induction of the release of acetylcholine [43].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.

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.

No MeSH data available.


Related in: MedlinePlus