Dataset Information

Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

ABSTRACT: Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses. In addition, in both studies antibiotics treatment resulted in (1) enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (2) divergent metabolic trajectories, with a 1,000-fold reduction in serum secondary bile acids, which was highly correlated with AP-1/NR4A signaling and inflammasome activation. Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.

SUBMITTER: Hagan T

PROVIDER: S-EPMC6750738 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

Hagan Thomas T Cortese Mario M Rouphael Nadine N Boudreau Carolyn C Linde Caitlin C Maddur Mohan S MS Das Jishnu J Wang Hong H Guthmiller Jenna J Zheng Nai-Ying NY Huang Min M Uphadhyay Amit A AA Gardinassi Luiz L Petitdemange Caroline C McCullough Michele Paine MP Johnson Sara Jo SJ Gill Kiran K Cervasi Barbara B Zou Jun J Bretin Alexis A Hahn Megan M Gewirtz Andrew T AT Bosinger Steve E SE Wilson Patrick C PC Li Shuzhao S Alter Galit G Khurana Surender S Golding Hana H Pulendran Bali B

Cell 20190901 6

Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significan ...[more]

PMID: 31491384

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Project description:Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of these microbial communities, yet studying the spatial organization of microbial communities at the single-cell level has been technically challenging. Here, we use the recently developed high-phylogenetic-resolution microbiota mapping by fluorescence in situ hybridization technology to image the gut microbiota at the species and single-cell level. We simultaneously image 63 different bacterial species to spatially characterize the perturbation and recovery of the gut microbiota to ampicillin and vancomycin in the cecum and distal colon of mice. To decipher the biology in this complex imaging data, we developed an analytical framework to characterize the spatial changes of the gut microbiota to a perturbation. The three-tiered analytical approach includes image-level diversity, pairwise colocalization analysis, and hypothesis-driven neighborhood analysis. Through this workflow, we identify biogeographic and antibiotic-based differences in the spatial organization of the gut microbiota. We demonstrate that the cecal microbiota has increased micrometer-scale diversity than the colon at baseline and recovers better from perturbation. Also, we identify potential foundation and keystone species that have high baseline neighborhood richness and that are associated with recovery from antibiotics. Through this workflow, we add a spatial layer to the characterization of bacterial communities and progress toward a better understanding of bacterial interactions leading to improved microbiome modulation strategies.ImportanceAntibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.

Dataset Information

Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

Publications

Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

Similar Datasets

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