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Childhood vaccines and antibiotic use in low- and middle-income countries 期刊论文
NATURE, 2020, 581 (7806) : 94-+
作者:  Louca, Stilianos;  Pennell, Matthew W.
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics(1-4). However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest(5). Here we show that vaccines that have recently been implemented in the World Health Organization'  s Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens(6,7). Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance(8).


Pneumococcal and rotavirus vaccines have reduced antibiotic consumption substantially among children under five years old in low- and middle-income countries  however, this effect could be doubled if all countries were to implement vaccination programmes and meet universal vaccine coverage targets.


  
Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier 期刊论文
NATURE, 2020, 579 (7800) : 575-+
作者:  Bhaduri, Aparna;  Andrews, Madeline G.;  Mancia Leon, Walter;  Jung, Diane;  Shin, David;  Allen, Denise;  Jung, Dana;  Schmunk, Galina;  Haeussler, Maximilian;  Salma, Jahan;  Pollen, Alex A.;  Nowakowski, Tomasz J.;  Kriegstein, Arnold R.
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

The intestinal mucosa serves both as a conduit for the uptake of food-derived nutrients and microbiome-derived metabolites, and as a barrier that prevents tissue invasion by microorganisms and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here we show in mice how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses that are controlled by type-3 innate lymphoid cells (ILC3)(1-3). Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP)(4). Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2  also known as VPAC2). Production of interleukin (IL)-22 by ILC3, which is upregulated by the presence of commensal microorganisms such as segmented filamentous bacteria(5-7), is inhibited upon engagement of VIPR2. As a consequence, levels of antimicrobial peptide derived from epithelial cells are reduced but the expression of lipid-binding proteins and transporters is increased(8). During food consumption, the activation of VIPergic neurons thus enhances the growth of segmented filamentous bacteria associated with the epithelium, and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic neuroimmune circuit in the intestine that promotes a trade-off between innate immune protection mediated by IL-22 and the efficiency of nutrient absorption. Modulation of this pathway may therefore be effective for enhancing resistance to enteropathogens(2,3,9) and for the treatment of metabolic diseases.


Feeding controls a neuroimmune circuit comprising VIP-producing neurons and type-3 innate lymphoid cells that helps to regulate the efficiency of nutrient uptake and IL-22-mediated immune protection in the intestine.