• 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

September 7, 2019
: The normal human
gut microbiome is a flourishing community of microorganisms,
some of which can affect the human immune system. In a new paper (Antibiotics-driven gut microbiome
perturbation alters immunity to vaccines in humans) 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 (USA).

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.

Research
team was compiled with two Indian originated scientists Surender Khurana & Amit
A. Upadhyay.

Surender
Khurana is affiliated with Division of Viral Products, Center for Biologics
Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993,
USA.

And

Amit A. Uphadhyay is affiliated with Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA

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