The intestinal mucosal barrier is composed of epithelial cells that are protected by an overlying host-secreted mucous layer and functions as the first line of defence against pathogenic and non-pathogenic microorganisms. Some microorganisms have evolved strategies to either survive in the mucosal barrier or circumvent it to establish infection. In this Review, we discuss the current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier, and we discuss strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer, as well as the role of defects in mucus production in chronic disease.

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Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. Apart from migraine, the age of the participants was an important predictive variable of intensity dependence. Analysis of individual differences revealed low sensitivity and moderate specificity of intensity dependence for migraine. Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache.

BackgroundElevated intraocular pressure (IOP), as well as fluctuations in IOP, is a main risk factor for glaucoma, but its pathogenic effect has not yet been clarified. Beyond the multifactorial pathology of the disease, autoimmune mechanisms seem to be linked to retinal ganglion cell (RGC) death. This study aimed to identify if intermittent IOP elevations in vivo (i) elicit neurodegeneration, (ii) provokes an immune response and (iii) whether progression of RGC loss can be attenuated by the B lymphocyte inhibitor Belimumab.MethodsUsing an intermittent ocular hypertension model (iOHT), Long Evans rats (n = 21) underwent 27 unilateral simulations of a fluctuating pressure profile. Nine of these animals received Belimumab, and additional seven rats served as normotensive controls. Axonal density was analyzed in PPD-stained optic nerve cross-sections. Retinal cross-sections were immunostained against Brn3a, Iba1, and IgG autoantibody depositions. Serum IgG concentration and IgG reactivities were determined using ELISA and protein microarrays. Data was analyzed using ANOVA and Tukey HSD test (unequal N) or student’s independent t test by groups.ResultsA wavelike IOP profile led to a significant neurodegeneration of optic nerve axons (−10.6 %, p < 0.001) and RGC (−19.5 %, p = 0.02) in iOHT eyes compared with fellow eyes. Belimumab-treated animals only showed slightly higher axonal survival and reduced serum IgG concentration (−29 %) after iOHT. Neuroinflammatory events, indicated by significantly upregulated microglia activation and IgG autoantibody depositions, were shown in all injured retinas. Significantly elevated serum autoantibody immunoreactivities against glutathione-S-transferase, spectrin, and transferrin were observed after iOHT and were negatively correlated to the axon density.ConclusionsIntermittent IOP elevations are sufficient to provoke neurodegeneration in the optic nerve and the retina and elicit changes of IgG autoantibody reactivities. Although the inhibition of B lymphocyte activation failed to ameliorate axonal survival, the correlation between damage and changes in the autoantibody reactivity suggests that autoantibody profiling could be useful as a biomarker for glaucoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0542-6) contains supplementary material, which is available to authorized users.

The change of dietary habits in Western societies, including reduced consumption of fiber, is linked to alterations in gut microbial ecology. Nevertheless, mechanistic connections between diet-induced microbiota changes that affect colonization resistance and enteric pathogen susceptibility are still emerging. We sought to investigate how a diet devoid of soluble plant fibers impacts the structure and function of a conventional gut microbiota in specific-pathogen-free (SPF) mice and how such changes alter susceptibility to a rodent enteric pathogen. We show that absence of dietary fiber intake leads to shifts in the abundances of specific taxa, microbiome-mediated erosion of the colonic mucus barrier, a reduction of intestinal barrier-promoting short-chain fatty acids, and increases in markers of mucosal barrier integrity disruption. Importantly, our results highlight that these low-fiber diet-induced changes in the gut microbial ecology collectively contribute to a lethal colitis by the mucosal pathogen Citrobacter rodentium , which is used as a mouse model for enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Our study indicates that modern, low-fiber Western-style diets might make individuals more prone to infection by enteric pathogens via the disruption of mucosal barrier integrity by diet-driven changes in the gut microbiota, illustrating possible implications for EPEC and EHEC infections.

The change of dietary habits in Western societies, including reduced consumption of fiber, is linked to alterations in gut microbial ecology. Nevertheless, mechanistic connections between diet-induced microbiota changes that affect colonization resistance and enteric pathogen susceptibility are still emerging. We sought to investigate how a diet devoid of soluble plant fibers impacts the structure and function of a conventional gut microbiota in specific-pathogen-free (SPF) mice and how such changes alter susceptibility to a rodent enteric pathogen. We show that absence of dietary fiber intake leads to shifts in the abundances of specific taxa, microbiome-mediated erosion of the colonic mucus barrier, a reduction of intestinal barrier-promoting short-chain fatty acids, and increases in markers of mucosal barrier integrity disruption. Importantly, our results highlight that these low fiber diet-induced changes in the gut microbial ecology collectively contribute to a lethal colitis by the mucosal pathogen Citrobacter rodentium, which is used as a mouse model for enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Our study indicates that modern, low-fiber Western diets might make individuals more prone to infection by enteric pathogens via the disruption of mucosal barrier integrity by diet-driven changes in the gut microbiota, illustrating possible implications for EPEC and EHEC infections.

Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy, yet little is known about how specific gut bacteria incite breakdown of oral tolerance. Here, we show that depriving specific-pathogen-free mice of dietary fiber leads to an increase of the mucolytic bacterium Akkermansia muciniphila, which is associated with a surge in the colonic type 2 immune cells and IgE-coated commensals, and microbiota-mediated gut mucosal barrier dysfunction. These changes manifest into exacerbated sensitization to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fiber deprivation, resulted in stronger anti-commensal IgE coating and type 2 immune responses, which worsened symptoms of food allergy. Our study supports a mechanistic link between diet and a mucolytic gut microbe in regulating food allergy.

Zusammenfassung: Die equine rezidivierende Uveitis (ERU) ist eine Entzündung der inneren, gefäßführenden Strukturen des Auges beim Pferd, die abwechselnd in akuten Schüben und entzündungsfreien Phasen oder als persistierende Entzündung verläuft. Als Ätiologie werden eine Infektion mit Leptospiren, eine Autoimmunerkrankung und eine genetische Komponente in der Literatur diskutiert. Neben der konservativen Therapie mit Medikamenten zur Behandlung der akuten Schübe, werden ein Ciclosporin-Implantat und eine Vitrektomie zur Vorbeugung weiterer Rezidive eingesetzt. Für die Vitrektomie sind Erfolgsraten von 73,6 % bis zu 100 % beschrieben. Seit 2005 wird alternativ eine intravitreale Injektion mit 4 mg Gentamicin als Therapieoption bei der ERU durchgeführt. Über die Wirkungsweise dieser intravitrealen Gentamicin-Injektion im Glaskörper sowie zur Elimination von Gentamicin aus dem Glaskörper von Pferden ist bisher wenig bekannt. Durch die Bindung von Gentamicin an Glaskörperproteine kann auch mit einer geringen Konzentration ein hoher und langanhaltender Wirkspiegel erreicht werden, der möglicherweise auch eine antibiotische Wirkung gegen noch vorhandene Leptospiren im Glaskörper einschließen könnte. Bisher liegen vier Studien über die Langzeit-Prognose in Bezug auf die Rezidivfreiheit nach Gentamicin-Injektion bei an ERU erkrankten Pferden vor. Die Erfolgsraten der intravitrealen Gentamicin-Injektion liegen zwischen 88,1 % und 98,6 % und sind mit denen nach einer Vitrektomie vergleichbar. Es wurden zwischen 18 und 86 Augen in einem Zeitintervall von einem bis 96 Monaten nach der Injektion ausgewertet. Die Sehkraft blieb nach intravitrealer Gentamicin-Injektion in Abhängigkeit von den Vorschädigungen in 33-78 % der Fälle erhalten. Es werden nur geringe Komplikationen während oder unmittelbar nach dem Eingriff beschrieben. Langfristig können Retina-Degenerationen ohne klinische Sehbeeinträchtigung, Phthisis bulbi und fortschreitende Kataraktformationen bis hin zur Erblindung beobachtet werden. Aufgrund diverser Vorteile für die Gentamicin-Injektion (Durchführbarkeit am stehenden, sedierten Pferd, Durchführbarkeit am stark vorgeschädigten Auge, geringer Kostenaufwand, geringe Komplikationsrate) kann diese Technik aufgrund der bisher vorliegenden Studienergebnissen neben der Vitrektomie als alternative Methode in der Behandlung der ERU gesehen werden.