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      Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms

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          Abstract

          The need for highly effective vaccines that induce robust and long-lasting immunity has never been more apparent. However, for reasons that are still poorly understood, immune responses to vaccination are highly variable between different individuals and different populations. Furthermore, vaccine immunogenicity is frequently suboptimal in the very populations who are at most risk from infectious disease, including infants, the elderly, and those living in low-income and middle-income countries. Although many factors have the potential to influence vaccine immunogenicity and therefore vaccine effectiveness, increasing evidence from clinical studies and animal models now suggests that the composition and function of the gut microbiota are crucial factors modulating immune responses to vaccination. In this Review, we synthesize this evidence, discuss the immunological mechanisms that potentially mediate these effects and consider the potential of microbiota-targeted interventions to optimize vaccine effectiveness.

          Abstract

          This Review discusses evidence from clinical studies and animal models regarding the effects of the gut microbiota on modulating immune responses to vaccination as well as the immunological mechanisms that potentially mediate these effects.

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          Most cited references104

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          Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.

          Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural African village of Burkina Faso (BF), where the diet, high in fiber content, is similar to that of early human settlements at the time of the birth of agriculture. By using high-throughput 16S rDNA sequencing and biochemical analyses, we found significant differences in gut microbiota between the two groups. BF children showed a significant enrichment in Bacteroidetes and depletion in Firmicutes (P < 0.001), with a unique abundance of bacteria from the genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for cellulose and xylan hydrolysis, completely lacking in the EU children. In addition, we found significantly more short-chain fatty acids (P < 0.001) in BF than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were significantly underrepresented in BF than in EU children (P < 0.05). We hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF individuals, allowing them to maximize energy intake from fibers while also protecting them from inflammations and noninfectious colonic diseases. This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide.
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            Is Open Access

            Global increase and geographic convergence in antibiotic consumption between 2000 and 2015

            Significance Antibiotic resistance, driven by antibiotic consumption, is a growing global health threat. Our report on antibiotic use in 76 countries over 16 years provides an up-to-date comprehensive assessment of global trends in antibiotic consumption. We find that the antibiotic consumption rate in low- and middle-income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries. However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.
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              Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

              The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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                Author and article information

                Contributors
                david.lynn@sahmri.com
                Journal
                Nat Rev Immunol
                Nat Rev Immunol
                Nature Reviews. Immunology
                Nature Publishing Group UK (London )
                1474-1733
                1474-1741
                17 May 2021
                : 1-14
                Affiliations
                [1 ]GRID grid.430453.5, ISNI 0000 0004 0565 2606, Precision Medicine Theme, South Australian Health and Medical Research Institute, ; Adelaide, South Australia Australia
                [2 ]GRID grid.1014.4, ISNI 0000 0004 0367 2697, Flinders Health and Medical Research Institute, , Flinders University, ; Bedford Park, South Australia Australia
                [3 ]GRID grid.168010.e, ISNI 0000000419368956, Stanford University School of Medicine, , Stanford University, ; Stanford, CA USA
                Author information
                http://orcid.org/0000-0003-4664-1404
                http://orcid.org/0000-0001-7345-6576
                http://orcid.org/0000-0003-4300-1380
                http://orcid.org/0000-0001-6517-4333
                Article
                554
                10.1038/s41577-021-00554-7
                8127454
                34002068
                446e95d7-24e2-44a6-9df6-04f74d622c76
                © Springer Nature Limited 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 12 April 2021
                Categories
                Review Article

                immunization,vaccines,microbiome
                immunization, vaccines, microbiome

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