The bodies of most animals are populated by highly complex and genetically diverse communities of microorganisms. The majority of these microbes reside within the intestines in largely stable but dynamically interactive climax communities that positively interact with their host. Studies from this laboratory have shown that stressor exposure impacts the stability of the microbiota and leads to bacterial translocation. The biological importance of these alterations, however, is not well understood. To determine whether the microbiome contributes to stressor-induced immunoenhancement, mice were exposed to a social stressor called social disruption (SDR), that increases circulating cytokines and primes the innate immune system for enhanced reactivity. Bacterial populations in the cecum were characterized using bacterial tag-encoded FLX amplicon pyrosequencing. Stressor exposure significantly changed the community structure of the microbiota, particularly when the microbiota were assessed immediately after stressor exposure. Most notably, stressor exposure decreased the relative abundance of bacteria in the genus Bacteroides, while increasing the relative abundance of bacteria in the genus Clostridium. The stressor also increased circulating levels of IL-6 and MCP-1, which were significantly correlated with stressor-induced changes to three bacterial genera (i.e., Coprococcus, Pseudobutyrivibrio, and Dorea). In follow up experiments, mice were treated with an antibiotic cocktail to determine whether reducing the microbiota would abrogate the stressor-induced increases in circulating cytokines. Exposure to SDR failed to increase IL-6 and MCP-1 in the antibiotic treated mice. These data show that exposure to SDR significantly affects bacterial populations in the intestines, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and remarkably also suggest that the microbiota are necessary for stressor-induced increases in circulating cytokines. NIH Public Access

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The paper aims to make a methodological contribution to the education segregation literature, providing a critique of previous measures of segregation used in the literature, as well as suggesting an alternative approach to measuring school segregation. It also provides new empirical evidence on changes in the extent of socio-economic segregation (measured by free school meals (FSM) entitlement) in English schools during the last fifteen years. Specifically, the paper examines Gorard et al.'s (2000aGorard et al.'s ( , 2003 finding that FSM segregation between schools fell significantly in the years following the 1988 Education Reform Act. Using Annual Schools Census data from 1989 to 2004, the paper challenges the magnitude of their findings, suggesting that the method used by Gorard et al. actually overstates the size of the fall in segregation by 100%. Our results show evidence of an increase in the index of dissimilarity in many Local Authorities, especially in London, although in the South-East as a whole we note that it falls. We also observe higher segregation in LEAs with higher proportions of pupils at voluntary-aided schools. We cannot confirm however, whether this is a causal relationship. It is not necessarily the case that the rise in the segregation index in these Local Authorities is attributable to the behaviour of VA schools. Much of this paper is a critique of previous methods used to measure segregation in schools. For example, we suggest that the GS index is not the optimal way of measuring changes in school segregation for the following reasons:1. GS is not bounded by 0 and 1: the upper boundary varies according to FSM eligibility, so GS is better described as an 'indicator' rather than an index of segregation; 2. GS is not symmetric, meaning that it is capable of showing that FSM segregation is rising and NONFSM segregation is falling simultaneously; and 3. GS is actually systematically variant to changes in overall FSM eligibility, except in the most stringent and unlikely of circumstances (the strict proportionate change in FSM); therefore we can properly describe it as composition variant. It had a tendency to fall as FSM eligibility rises, regardless of the change in the unevenness of school's shares of FSM and NONFSM pupils.In this paper we make the case for a segregation curve approach to measuring segregation and use one exemplar index, the index of Dissimilarity, to re-evaluate the extent of school segregation in England over the last fifteen years. What can we conclude?• There was no pervasive increase in segregation over the period.• There are a number of potential explanations for this. For example, it may be that de facto school choice did not in fact increase during this period due to capacity constraints.• The analysis does however provide clear evidence of an increase in segregation, as measured by the index of dissimilarity, in many Local Authorities, particularly in London. The index is also higher in LEAs with higher proportions of pupils educated at voluntary-aided schools...

This study examines the proposition that secondary school choice in England has produced a stratified education system, compared with a counterfactual world where pupils are allocated into schools based strictly on proximity via a simulation that exploits the availability of pupil postcodes in the National Pupil Database. The study finds current levels of sorting in the English secondary school system-defined as pupils who do not attend their proximity allocation school-to be around 50 per cent, but estimates that only one-in-five pupils are potentially active in sorting between non-faith comprehensive schools. School segregation is almost always lower in the proximity counterfactual than in the actual data, confirming that where pupils are sorting themselves into a non-proximity school, it does tend to increase social and ability segregation. The difference between school and residential segregation is greatest in urban areas and LEAs with many pupils in grammar and voluntary-aided schools.

The indigenous microbiota impact mucosal, as well as systemic, immune responses, but whether the microbiota are involved in stressor-induced immunomodulation has not been thoroughly tested. A well characterized murine stressor, called social disruption (SDR), was used to study whether the microbiota are involved in stressor-induced enhancement of macrophage reactivity. Exposure to the SDR stressor enhanced the ability of splenic macrophages to produce microbicidal mediators (e.g., inducible nitric oxide synthase (iNOS), superoxide anion, and peroxynitrite) and to kill target Escherichia coli. Exposure to the SDR stressor also increased cytokine production by LPS-stimulated splenic macrophages. These effects, however, were impacted by the microbiota. Microbicidal activity and cytokine mRNA in splenic macrophages from Swiss Webster germfree mice that lack any commensal microbiota were not enhanced by exposure to the SDR stressor. However, when germfree mice were conventionalized by colonizing them with microbiota from CD-1 conventional donor mice, exposure to the SDR stressor again increased microbicidal activity and cytokine mRNA. In follow up experiments, immunocompetent conventional CD-1 mice were treated with a cocktail of antibiotics to disrupt the intestinal microbiota. While exposure to the SDR stressor enhanced splenic macrophage microbicidal activity and cytokine production in vehicle-treated mice, treatment with antibiotics attenuated the SDR stressor-induced increases in splenic macrophage reactivity. Treatment with antibiotics also prevented the stressor-induced increase in circulating levels of bacterial peptidoglycan, suggesting that translocation of microbiota-derived peptidoglycan into the body primes the innate immune system for enhanced activity. This study demonstrates that the microbiota play a crucial role in stressor-induced immunoenhancement.