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

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  • Cell: Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans

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

    Photo Credit - CDC PHIL


    One of the challenges with current flu vaccines is that the cohort most in need of its protection - those over the age of 65 - often generate a sub-optimal immune response from the shot (see PLoS One: Limited Effectiveness Of Flu Vaccines In The Elderly & Flu Shots And The Elderly).
    While that doesn't negate the value of getting the vaccine (see CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly), it does reduce its effectiveness.
    Over the years we've looked at research into reasons why those over 65 might be inclined to mount a lower immune response, and while physiological changes that come with ageing are at the top of the list, certain medications commonly taken by the elderly have been suspect as well.
    Today we've a new study published in Cell by researchers out of Stanford, funded by NIAID, that looked at two small groups of test subjects (n=22 & n=11) over two flu seasons, half of whom received a 5-day course of broad spectrum antibiotics prior to getting a flu vaccine.

    Most of those receiving the course of antibiotics saw a significant decrease in gut bacteria and immune changes that promoted a pro-inflammatory state (mimicking a condition commonly seen in the elderly).

    The first cohort had high baseline levels of neutralizing antibodies to the flu strain being tested, while the second cohort did not. The authors wrote:
    In subjects with high baseline titers, there was minimal impact on the antibody response, but in the second cohort of subjects with low baseline titers we observed a striking impact of antibiotics treatment on the amount of H1N1-specific IgG1 following vaccination
    While at first glance this may appear a cautionary tale about antibiotic use, it is really more about how our gut microbiome impacts our immune response as we age.

    First, a press release from the NIH, then a link to the full Cell research article.
    Friday, September 6, 2019
    Disrupting the gut microbiome may affect some immune responses to flu vaccination

    The normal human gut microbiome is a flourishing community of microorganisms, some of which can affect the human immune system. In a new paper published this week in Cell, researchers found that oral antibiotics, which can kill gut microorganisms, can alter the human immune response to seasonal influenza vaccination. The work was led by scientists at Stanford University and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

    The research team examined 33 healthy adult participants in their study. One group of 22 volunteers was studied during the 2014-2015 flu season, and the second group with 11 volunteers was studied during the 2015-2016 flu season. The group of 22 volunteers had high pre-existing immunity to the influenza virus strains contained in the 2014-2015 seasonal influenza vaccine. The group of 11 volunteers had low immunity to the 2015-2016 seasonal influenza vaccine’s virus strains.

    All study participants received a seasonal influenza vaccine. Half the participants in each group also received a five-day course of a broad-spectrum antibiotic regimen (consisting of neomycin, vancomycin, and metronidazole) by mouth before receiving the vaccine. By analyzing stool and blood serum samples taken at various times up to one year after vaccination, the researchers tracked the participants’ immune response to the influenza vaccines, as well as the diversity and abundance of the organisms in their gut microbiomes.

    As expected, most participants who received antibiotics experienced reduced levels of gut bacteria. In addition, among the 2015-2016 participants who had little prior immunity to the seasonal influenza virus vaccine strains, a course of antibiotics hindered their immune responses to one of the three influenza virus strains in the vaccine, an H1N1 A/California-specific virus. This likely indicates that should they be exposed to this H1N1 virus after vaccination, these participants would be less protected against infection with that strain than people who had not received antibiotics, according to the authors. This finding supports earlier research results in mice.

    The researchers also found that people who took antibiotics experienced changes to their immune systems that promoted a pro-inflammatory state, similar to a condition seen in older adults who have received influenza vaccines.
    The investigators believe this pro-inflammatory state is related to the process by which the microbiome regulates the metabolism of bile acid—with fewer microorganisms, this process is disrupted. Humans’ microbiomes change naturally as they age, and the researchers suggest that further research on these pathways could provide insights into why older adults respond differently to influenza vaccination and why they have weaker immune systems overall.
    T Hagan et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell DOI: 10.1016/j.cell.2019.08.010 (2019).
    (Continue . . . )

    The full, and quite detailed, article is available at the link below:
    Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans

    Thomas Hagan, Mario Cortese, Nadine Rouphael, Carolyn Boudreau, Caitlin Linde, Mohan S. Maddur, Jishnu Das, Hong Wang, Jenna Guthmiller, Nai-Ying Zheng, Min Huang, Amit A. Uphadhyay, Luiz Gardinassi, Caroline Petitdemange, Michele Paine McCullough, Sara Jo Johnson, Kiran Gill, Barbara Cervasi, Jun Zou, Alexis Bretin, Megan Hahn, Andrew T. Gewirtz, Steve E. Bosinger, Patrick C. Wilson, Shuzhao Li, Galit Alter, Surender Khurana, Hana Golding, Bali Pulendran


    •Microbiome loss impairs antibody response in subjects with low pre-existing immunity
    •Antibiotics treatment leads to enhanced inflammatory signatures in the blood
    •Loss of secondary bile acids is linked to AP-1/NR4A and inflammasome activation
    •Integrative analysis reveals divergent mechanisms of microbiome influence on immunity

    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.
    (Continue . . . )
    All medical discussions are for educational purposes. I am not a doctor, just a retired paramedic. Nothing I post should be construed as specific medical advice. If you have a medical problem, see your physician.