Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial

Harris, Vanessa; Haak, Bastiaan W.; Handley, Scott A.; Jiang, Baoming; Velásquez, Daniel E.; Hykes, Barry L.; Droit, Lindsay; Berbers, Guy A. M.; Kemper, E. Marleen; Leeuwen, Ester M. M. van; Hensbroek, Michaël Boele van; Wiersinga, W. Joost

doi:10.1016/j.chom.2018.07.005

Cited by 98 publications

(108 citation statements)

References 34 publications

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“…Furthermore, it has been indicated that early-life gut microbiota dysbiosis damages vaccine immune responses [49,50]. In this study, we found that early-life intervention with FMT-CS can reduce the risk of gut microbiota dysbiosis, as well as improve the antibody levels of M.hyo and PCV2.…”

Section: Early-life Intervention With Fmt-cs Promotes the Developmentmentioning

confidence: 60%

Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

Xiang

Pan

et al. 2020

IJMS

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Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a "window of opportunity" for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.

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Section: Early-life Intervention With Fmt-cs Promotes the Developmentmentioning

confidence: 60%

Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

Xiang

Pan

et al. 2020

IJMS

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“…While there is evidence for a beneficial effect of probiotics on vaccine responses, to date, only one study has investigated the effect of antibiotics on vaccine responses in humans. This study reported that administration of antibiotics before vaccination did not alter serum immunoglobulin (Ig) A concentrations to oral rotavirus vaccine (ORV) in adults …”

Section: Introductionmentioning

confidence: 99%

“…This study reported that administration of antibiotics before vaccination did not alter serum immunoglobulin (Ig) A concentrations to oral rotavirus vaccine (ORV) in adults. 5 Determining the influence of intrinsic and extrinsic factors on vaccine antibody responses has implications for optimising vaccine recommendations and individualising vaccine schedules.…”

Section: Introductionmentioning

confidence: 99%

Biological sex influences antibody responses to routine vaccinations in the first year of life

et al. 2019

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Aim We investigated the effect of early‐life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. Methods One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early‐life factor. Results Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. Conclusion There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.

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“…Our data demonstrate that pathogen-specific MAbs do not reduce the absolute abundance, diversity, or taxonomic composition of the gut microbiome compared to those with the effects of antibiotic treatment. Such effects observed in the antibiotic treatment groups are indicative of a reduced bacterial burden in the gut and diminished capacity to prevent infection by opportunistic pathogens (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function

Jones-Nelson

Tovchigrechko

Glover

et al. 2020

Antimicrob Agents Chemother

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Antibiotics revolutionized the treatment of infectious diseases; however, it is now clear that broad-spectrum antibiotics alter the composition and function of the host’s microbiome. The microbiome plays a key role in human health, and its perturbation is increasingly recognized as contributing to many human diseases. Widespread broad-spectrum antibiotic use has also resulted in the emergence of multidrug-resistant pathogens, spurring the development of pathogen-specific strategies such as monoclonal antibodies (MAbs) to combat bacterial infection. Not only are pathogen-specific approaches not expected to induce resistance in nontargeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen-specific MAbs, and their controls (saline or control IgG [c-IgG]) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites, including short-chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific MAbs, was no different from that with animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha and beta diversity, of the fecal microbiome and bacterial metabolites in the feces of all antibiotic-treated mice. Taken together, these results indicate that pathogen-specific MAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more-targeted approach to antibacterial therapy.

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Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial

Cited by 98 publications

References 34 publications

Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

Biological sex influences antibody responses to routine vaccinations in the first year of life

Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function

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