Interconnected microbiomes and resistomes in low-income human habitats

Pehrsson, Erica C.; Tsukayama, Pablo; Patel, Sanket; Mejía-Bautista, Melissa; Sosa-Soto, Giordano; Navarrete, Karla Margarita; Calderón, Maritza; Cabrera, Lilia; Hoyos-Arango, William; Bértoli, Marta; Berg, Douglas E.; Gilman, Robert H.; Dantas, Gautam

doi:10.1038/nature17672

Cited by 442 publications

(421 citation statements)

References 46 publications

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“…The composition of the bacterial microbiota displays considerable variation by geographic setting [150][151][152], lifestyle [153] and season [154]. As such, the ecological landscape into which an oral vaccine is introduced is likely to vary considerably between infants in high-and low-income countries.…”

Section: The Commensal Microbiotamentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

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Section: The Commensal Microbiotamentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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“…Our endemic microbiome can mitigate pathogens and pathogenicity by ecological niche exclusion and pro-inflammatory or proliferation signal inhibitions [118, 126]. In doing so, our microbiome also acts as a cohesive unit by exchanging genetic elements such as antibiotic resistance genes (ARGs) [56•, 104, 127, 128•, 129–131] or by metabolic cross-feeding to influence community structure and mitigate ecological collapse. Increasingly, we realize that our modern behaviors have changed the selective environment and transmission of our microbiome through sanitization and a lack of exposure to environmental or infectious agents, a concept embedded in the now classic ‘hygiene hypothesis’ [132, 133].…”

Section: Role Of the Microbiome In Human Biology And Evolutionmentioning

confidence: 99%

“…( d ) The placenta harbors an oral-like microbiome [32]; oral and vaginal dysbioses increase risk for preterm labor and stillbirth [33, 34]. ( e ) Human microbiota are hotspots for horizontal gene transfer [128•, 129–131]; antibiotic resistance genes in oral and gut microbiota predate the use of therapeutic antibiotics [56•, 104, 127]. ( f ) Ecological structure of the vaginal microbiome influences risk for contracting sexually transmitted infections [137••].…”

Section: Figurementioning

confidence: 99%

Insights into human evolution from ancient and contemporary microbiome studies

Schnorr

Sankaranarayanan

Lewis

et al. 2016

Current Opinion in Genetics & Development

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Over the past decade, human microbiome research has energized the study of human evolution through a complete shift in our understanding of what it means to be human. The microbiome plays a pivotal role in human biology, performing key functions in digestion, mood and behavior, development and immunity, and a range of acute and chronic diseases. It is therefore critical to understand its evolution and changing ecology through time. Here we review recent findings on the microbiota of diverse human populations, non-human primates, and past human populations and discuss the implications of this research in formulating a deeper evolutionary understanding of the human holobiont.

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“…Many resistance genes were found, were widely disseminated, and were often tightly associated with transposase-or phage integrase-like sequences. 73 This points once again to a likely role of mobile DNA elements in dissemination of resistance in bacterial populations. 73 Would I have studied drug resistance in H. pylori and/or embraced a study with Gautam on developing country resistomes had I not worked with and learned so much from Julian?…”

Section: Drug Resistance In H Pylorimentioning

confidence: 97%

Julian Davies and the discovery of kanamycin resistance transposon Tn5

Berg

2016

J Antibiot

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This paper recounts some of my fond memories of a collaboration between Julian Davies and myself that started in 1974 in Geneva and that led to our serendipitous discovery of the bacterial kanamycin resistance transposon Tn5, and aspects of the lasting positive impact of our interaction and discovery on me and the community. Tn5 was one of the first antibiotic resistance transposons to be found. Its analysis over the ensuing decades provided valuable insights into mechanisms and control of transposition, and led to its use as a much-valued tool in diverse areas of molecular genetics, as also will be discussed here. The Journal of Antibiotics (2017) 70, 339-346; doi:10.1038/ja.2016.120; published online 12 October 2016 BACKGROUND It was wonderfully educational, productive and exciting for me to work with Julian Davies for a few years in the mid 1970s, doing experiments that led to the serendipitous discovery and initial characterizations of kanamycin resistance transposon Tn5 1 -one of the first and most useful of the many bacterial antibiotic resistance (AR) transposons that have been found. 2 I was inspired by Julian's knowledge of mechanisms of antibiotic action and resistance mechanisms, his creativity and clarity of thought and expression, as illustrated in his numerous papers, 3-6 and by his high energy, kindness and inventive good humor-traits that have enriched the lives and careers of many people over the years. Described here, in tribute to Julian and his special character, are my memories of a collaboration that led to Tn5's unexpected discovery, Tn5's properties, and some lasting impacts of our collaboration on the field and on me personally.We began interacting in 1974, soon after Julian arrived in Geneva to begin his sabbatical with Pierre Francois Spahr (Department of Molecular Biology of the University). 7 I was then in my fourth (final) year as Chargé de Recherche (senior postdoc) in Lucien Caro's group in the same department, studying λdv plasmids, often in collaboration with Grete Kellenberger-Gujer, also in Lucien's group 8-13 -and during these years, also hugely enjoying features in and out of the lab that have drawn researchers to Geneva for decades: a superb scientific atmosphere, year-round easy access to the exquisite Alps and Jura mountains, and the language, cuisine and culture of Geneva and vicinity. I had become intrigued the year before by Julian's ideas about origins and evolution of resistance genes, as described in his paper with Raoul Benveniste. 14 They advanced the then-novel theory that the types of bacteria that had provided life saving antibiotics were also the ancestral sources of AR genes that were becoming increasingly common in human and veterinary pathogens. Their inferences were

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Interconnected microbiomes and resistomes in low-income human habitats

Cited by 442 publications

References 46 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Insights into human evolution from ancient and contemporary microbiome studies

Julian Davies and the discovery of kanamycin resistance transposon Tn5

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