Early-life exposure to gut microbiota from disease protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice

The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible non-obese diabetic (NOD) mice have been shown to harbour a distinct microbiota to disease protected mice. We hypothesised that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6 derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before birth, resulted in moderate changes to the gut microbiota, whereas initiating co-housing at weaning only led to minimal changes. Terminating cohousing at weaning reduced the changes in the microbiota composition. However, diabetes onset was not significantly delayed and there was no reduction in intestinal inflammation or the proportion of regulatory T cells in the co-housed NOD mice. However, insulin but not IGRP-specific CD8+ T cells were reduced by co-housing suggesting an epitope-specific modulation of the autoreactive response by the gut microbiota. These results suggest that the T1D susceptible genetic background of the NOD mouse was resistant to the introduction of a C57BL/6 derived microbiota. This article is protected by copyright. All rights reserved

A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space

Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space

Wasting Breath in Hamlet

This is the final version. Available on open access from Palgrave via the DOI in this recordThis chapter draws on instances of disordered breathing in Hamlet in order to examine the cultural signifcance of sighs in the early modern period, as well as in the context of current work in the feld of medical humanities. Tracing the medical history of sighing in ancient and early modern treatises of the passions, the chapter argues that sighs, in the text and the performance of the tragedy, exceed their conventional interpretation as symptoms of pain and disrupt meaning on the page and on stage. In the light of New Materialist theory, the air circulating in Hamlet is shown to dismantle narratives of representation, posing new questions for the future of medical humanities

Biotransformation of glucosinolates from a bacterial perspective

Epidemiological studies have shown an association between the consumption of cruciferous vegetables and a reduced risk of certain types of cancers, in particular, pancreatic, bladder and colorectal. This is thought to be the result of the conversion of glucosinolates (GSLs) present in the vegetables into bioactive isothiocyanates (ITCs) that in turn stimulate a host response involving detoxification pathways. Conversion of GSLs is catalysed by the enzyme myrosinase, co-produced by the plant but stored in separate tissue compartments and brought together when the tissue is damaged. Myrosinase activity can be lost during storage of vegetables and is often inactivated by cooking. In the absence of active plant myrosinase the host's gut bacteria are capable of carrying out a myrosinase-like activity on GSLs in the lower gut. Several micro-organisms are known to be capable of metabolizing GSLs leading to the production of ITCs and nitriles, and this review examines the bacterial biotransformation of GSLs and a role for the microbiota in their biotransformation

Lactic acid bacteria convert glucosinolates to nitriles efficiently yet differently from enterobacteriaceae

Glucosinolates from the genus Brassica can be converted into bioactive compounds known to induce phase II enzymes, which may decrease the risk of cancers. Conversion via hydrolysis is usually by the brassica enzyme myrosinase, which can be inactivated by cooking or storage. We examined the potential of three beneficial bacteria, Lactobacillus plantarum KW30, Lactococcus lactis subsp. lactis KF147, and Escherichia con Nissle 1917, and known myrosinase-producer Enterobacter cloacae to catalyze the conversion of glucosinolates in broccoli extract. Enterobacteriaceae consumed on average 65% glucoiberin and 78% glucoraphanin, transforming them into glucoiberverin and glucoerucin, respectively, and small amounts of iberverin nitrile and erucin nitrile. The lactic acid bacteria did not accumulate reduced glucosinolates, consuming all at 30-33% and transforming these into iberverin nitrile, erucin nitrile, sulforaphane nitrile, and further unidentified metabolites. Adding beneficial bacteria to a glucosinolate-rich diet may increase glucosinolate transformation, thereby increasing host exposure to bioactives

Correction to: Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota

Abstract Following publication of the original article [1] it came to the attention of the Production Editor that Figs. 1 and 2 had not been replaced with the newly revised figures supplied by the authors (the originals being unusable due to poor quality image and text)