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

Supporting Information S1 File. Microbiota Data Set. NS.S, NS.LD, NS.HD stand for non-separated Saline, non-separated Low Dose, non-separated High Dose, respectively. MS.S, MS.LD, MS.HD stand for maternally separated Saline, maternally separated Low Dose, maternally separated High Dose, respectively. (ZIP)peer-reviewedBackground 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.Research was funded by Food Institutional Research Measure (FIRM) under Grant No. 10/RD/TMFRC/709, the APC Microbiome Institute under Grant No. 07/CE/B1368 and 12/RC/2273, Science Foundation Ireland (SFI) under Grant No. 12/IA/1537

Banking union in historical perspective: the initiative of the European Commission in the 1960s-1970s

This article shows that planning for the organization of EU banking regulation and supervision did not just appear on the agenda in recent years with discussions over the creation of the eurozone banking union. It unveils a hitherto neglected initiative of the European Commission in the 1960s and early 1970s. Drawing on extensive archival work, this article explains that this initiative, however, rested on a number of different assumptions, and emerged in a much different context. It first explains that the Commission's initial project was not crisis-driven; that it articulated the link between monetary integration and banking regulation; and finally that it did not set out to move the supervisory framework to the supranational level, unlike present-day developments

Estrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: Effects of early-life stress

Background: Early-life stress (ELS) is a recognized risk factor for chronic pain disorders, and females appear to be more sensitive to the negative effects of stress. Moreover, estrous cycle-related fluctuations in estrogen levels have been linked with alternating pain sensitivity. Aberrant central circuitry involving both the anterior cingulate cortex (ACC) and the lumbosacral spinal cord has also been implicated in the modulation of visceral pain in clinical and preclinical studies. Here we further investigate changes in visceral pain sensitivity and central glutamatergic systems in rats with respect to estrous cycle and ELS. Methods: We investigated visceral sensitivity in adult female Sprague-Dawley rats, which had undergone maternal separation (MS) in early life or remained non-separated (NS), by performing colorectal distension (CRD). We also assessed excitatory amino acid uptake through excitatory amino acid transporters (EAATs) in the lumbosacral spinal cord and ACC. Results: NS animals in proestrus and estrus exhibited reduced EAAT uptake and decreased threshold to CRD. Moreover, total pain behaviors were increased in these stages. MS rats exhibited lower pain thresholds and higher total pain behaviors to CRD across all stages of the estrous cycle. Interestingly, cortical EAAT function in MS rats was inhibited in the low estrogen state—an effect completely opposite to that seen in NS rats. Conclusions: This data confirms that estrous cycle and ELS are significant factors in visceral sensitivity and fluctuations in EAAT function may be a perpetuating factor mediating central sensitization

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

peer-reviewedThe aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.The authors and their work were supported by the APC Microbiome Institute. The APC Microbiome Institute is funded by Science Foundation Ireland (SFI). This publication has emanated from research supported by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2273

Effects of climate change and anthropogenic modification on a disturbance-dependent species in a large riverine system

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecosphere 8 (2017): e01653, doi:10.1002/ecs2.1653.Humans have altered nearly every natural disturbance regime on the planet through climate and land-use change, and in many instances, these processes may have interacting effects. For example, projected shifts in temperature and precipitation will likely influence disturbance regimes already affected by anthropogenic fire suppression or river impoundments. Understanding how disturbance-dependent species respond to complex and interacting environmental changes is important for conservation efforts. Using field-based demographic and movement rates, we conducted a metapopulation viability analysis for piping plovers (Charadrius melodus), a threatened disturbance-dependent species, along the Missouri and Platte rivers in the Great Plains of North America. Our aim was to better understand current and projected future metapopulation dynamics given that natural disturbances (flooding or high-flow events) have been greatly reduced by river impoundments and that climate change could further alter the disturbance regime. Although metapopulation abundance has been substantially reduced under the current suppressed disturbance regime (high-flow return interval ~ 20 yr), it could grow if the frequency of high-flow events increases as predicted under likely climate change scenarios. We found that a four-year return interval would maximize metapopulation abundance, and all subpopulations in the metapopulation would act as sources at a return interval of 15 yr or less. Regardless of disturbance frequency, the presence of even a small, stable source subpopulation buffered the metapopulation and sustained a low metapopulation extinction risk. Therefore, climate change could have positive effects in ecosystems where disturbances have been anthropogenically suppressed when climatic shifts move disturbance regimes toward more historical patterns. Furthermore, stable source populations, even if unintentionally maintained through anthropogenic activities, may be critical for the persistence of metapopulations of early-successional species under both suppressed disturbance regimes and disturbance regimes where climate change has further altered disturbance frequency or scope.Nebraska Environmental Trust Nebraska State Wildlife Grant Program; Nebraska Wildlife Conservation Fund; U.S. Army Corps of Engineers; U.S. Fish and Wildlife Service (USFWS); USFWS North Atlantic Landscape Conservation Cooperative; Virginia Tec

Effects of climate change and anthropogenic modification on a disturbance-dependent species in a large riverine system

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecosphere 8 (2017): e01653, doi:10.1002/ecs2.1653.Humans have altered nearly every natural disturbance regime on the planet through climate and land-use change, and in many instances, these processes may have interacting effects. For example, projected shifts in temperature and precipitation will likely influence disturbance regimes already affected by anthropogenic fire suppression or river impoundments. Understanding how disturbance-dependent species respond to complex and interacting environmental changes is important for conservation efforts. Using field-based demographic and movement rates, we conducted a metapopulation viability analysis for piping plovers (Charadrius melodus), a threatened disturbance-dependent species, along the Missouri and Platte rivers in the Great Plains of North America. Our aim was to better understand current and projected future metapopulation dynamics given that natural disturbances (flooding or high-flow events) have been greatly reduced by river impoundments and that climate change could further alter the disturbance regime. Although metapopulation abundance has been substantially reduced under the current suppressed disturbance regime (high-flow return interval ~ 20 yr), it could grow if the frequency of high-flow events increases as predicted under likely climate change scenarios. We found that a four-year return interval would maximize metapopulation abundance, and all subpopulations in the metapopulation would act as sources at a return interval of 15 yr or less. Regardless of disturbance frequency, the presence of even a small, stable source subpopulation buffered the metapopulation and sustained a low metapopulation extinction risk. Therefore, climate change could have positive effects in ecosystems where disturbances have been anthropogenically suppressed when climatic shifts move disturbance regimes toward more historical patterns. Furthermore, stable source populations, even if unintentionally maintained through anthropogenic activities, may be critical for the persistence of metapopulations of early-successional species under both suppressed disturbance regimes and disturbance regimes where climate change has further altered disturbance frequency or scope.Nebraska Environmental Trust Nebraska State Wildlife Grant Program; Nebraska Wildlife Conservation Fund; U.S. Army Corps of Engineers; U.S. Fish and Wildlife Service (USFWS); USFWS North Atlantic Landscape Conservation Cooperative; Virginia Tec

Drunk bugs: chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice

The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N = 10) or air (Control, N = 9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p < 0.05) and beta (p < 0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p < 0.001) and significant reductions in genra Clostridium IV and XIVb (p < 0.001), Dorea (p < 0.01), and Coprococcus (p < 0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress

Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free mice highlight the extreme impact on brain health that results from life without commensal microbes, however the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male Sprague Dawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, increased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found change in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of BDNF, a hallmark of altered microbiota-gut-brain axis signaling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations

Revolving doors, accountability and transparency - emerging regulatory concerns and policy solutions in the financial crisis

It is a common phenomenon in all areas of regulation that regulators become captured by the industry they regulate, meaning that they take on the objectives of management in the firms they regulate. They may thereby lose sight of the ultimate objectives of regulation. Regulatory capture is particularly serious in industries such as banking where there is a conflict of interest between the firms‘ objectives (to maximise profits) and the objectives of the regulation

Analysis of the UK Government's 2011 tourism policy

This review considers the UK Government's 2011 tourism policy document. The policy was produced during a period of public sector restructuring in the UK and also during the global economic crisis, which began in 2008. The policy sets out a number of reforms to the governance of tourism at the national and local levels, which aim to increase the level of private sector involvement in leading and developing the tourism sector and to reduce the sector's dependence on public funding. During a period of economic slowdown in the UK, the tourism industry can make a significant contribution to growth, but it is not yet clear whether these proposed reforms will support or impede the future development of the tourism industry in the UK