The Bacterial Microbiome and Immune Response to Vaccines

I love it when one of my readers contacts me to talk about a post, to show me something new or just wants to introduce him or herself and say hi.  As I’ve pointed out recently on the Biome Buzz Facebook page, we are all here to learn, bearing mind, always, that science does not yet have all the answers.

Now an introductory side note, before I describe the research I read these past couple of days:

As the parent of a young man with autism – who had a horrendous physical and behavior regression in his 2^nd year of life – it would be all too easy for me to jump to conclusions regarding the cause.  After all, it feels good to have something to blame. However, I maintain scientific objectivity because that really is the only way to someday uncover the truth.  That there is a massive increase in the rates of autism, as well as allergy, autoimmunity and other immune-mediated diseases in our society is irrefutable.  No one disagrees with that. The WHY of it though, is simply not yet known.  And as I’ve written about before, it’s NOT going to be a simple solution:  undoubtedly, the answer will turn out to be a complex interplay of many factors.

So keeping our scientific objectivity in at the forefront, I am writing today about what we know – and mainly don’t know – about the relationship of the bacterial microbiome to vaccine response.

A couple of days ago, I got a message from a reader who runs a website devoted to increasing awareness of the importance of the bacterial microbiota to health.  One focus of The Gut Club is to forward real scientific research into the connection between adverse vaccine reaction and an altered gut microbiome. He wanted to know if I’d write about the subject, and my first reaction was…no way!  I am not touching that one with a 10-foot pole!  I have enough stress in my life and my blog is supposed to be one of my fun hobbies…not a source of aggravation. But science is science, so I still took the time to see what his site was about, and to read the short paper he recently co-authored with two scientists.[i]

As it turns out, scientists are starting to look at the effects of biome alterations on response to vaccines.  This is not controversial at all.  When you consider that at least 70% of your immune system is in your gut, and the crucial role we now know the gut flora plays in immunity, it makes perfectly logical sense that there may be a connection, especially considering the variability in immune responses to vaccines. Some people require only 1 to achieve a lifetime of immunity while other people need to be re-inoculated multiple times, while still others never gain immunity at all.  Why that is, no one knows, but scientists are starting to suspect that gut bacterial variability is a key factor.  And this is the crux of today’s post.

The short paper Keith co-authored simply asks the question, “Do gut microbiota mediate adverse vaccine reaction?” which is a fair question since, again, there is no argument that some people do react poorly to vaccines. The paper’s central hypothesis is, “…that gut microbiota have a significant effect on host response to vaccination where a reduced or absent population of commensal flora coupled with an overgrowth of pathogenic strains may become a microbial predisposition to adverse vaccine reaction.”  It goes on to give a brief summary of some of the science substantiating that idea.  For example, Dr. Lijuan Yuan, another co-author – who runs a lab at the Virginia-Maryland College of Veterinary Medicine – has developed a pig model that has been used to test the connection between vaccine reaction and biome alterations.  In one study, they found that “…vaccinated UHMG [unhealthy] pigs had higher viral shedding titres and more severe clinical signs compared to HHGM [healthy] pigs after virulent HRV [rotovirus vaccine] challenge.”

The paper is a call for more research: enough evidence currently exists to merit serious scientific inquiry into this connection.

In the interest of time, I selected to read just one of the papers listed in the bibliography, and found that indeed, there is research out there connecting biome alterations to vaccine response. By response, I mean whether or not the vaccine works to confer adequate immunity.  The paper I selected was authored in 2018 by a scientist from a major Australian University and one from Stanford University School of Medicine.[ii] They note from the start that vaccine response (i.e. the generation of antibodies by the individual) is “highly variable,” and that emerging science currently shows that the “…gut microbiome plays a key role in shaping systemic immune responses to both orally and parenterally [elsewhere in the body, besides the digestive tract – so via shot, in chis case] administered vaccines.”

To illustrate the first point, vaccine response variability, they provide several examples including: 1. the response to the yellow fever vaccine “…can vary by more than 10-fold” while, 2. response to the seasonal influenza vaccine “…can vary by more than 100-fold.”  Incredible, right?  A randomized trial of 1709 infants in the USA, vaccinated with the pneumococcal conjugate vaccine (PCV), indicated, “…considerable variation in the response between infants.”

These authors go on to point out that antibiotic exposure profoundly alters the composition of the microbiota and can “…lead to a long-lasting loss of diversity and dysregulation of the microbiome…” Dysbiosis very early in life, as you all know, is already associated with life-long inflammatory illnesses like allergy and obesity, and has profound impact on systemic immunity.  They go to say that, “Several lines of evidence now suggest that antibiotics can modulate vaccine responses.”

These 2 scientists explain that right now, the “…most convincing evidence in mice to date that the microbiota can influence vaccine responses is a study of mice immunized with the seasonal influenza vaccine that showed that germ-free or antibiotic-treated mice had significantly impaired IgG and IgM antibody responses to this vaccine.”

One of the most significant sentences in this paper, to my mind, is in a paragraph discussing the metabolites produced by gut bacteria, including pro-inflammatory LPS (lipopolysaccharides – which are often used in experimentation to induce inflammation in the intestines and which are known to contribute to autoimmunity in humans).  They state that while it is not currently known whether or not LPS can influence vaccine response, it is entirely possible:  “…the immunomodulatory activity of LPS produced by the microbiota may be particularly relevant if vaccines are administered after antibiotics.  Antibiotic exposure is commonly associated with a subsequent overgrowth of specific species of bacteria, such as members of the Enterobacteriacceae, which produce high levels of endotoxin (LPS).”  That is, antibiotics not only alter the gut microbiota, but in doing so, often lead to excessively high levels of proinflammatory LPS toxins, further altering the immune status of the individual.  The response to a vaccine at that point may subsequently be radically altered.  They go on to state:  “Further work is now necessary to determine whether immune responses to vaccines are altered in mice or people who have been recently exposed to antibiotics and have high levels of gut dysbiosis.”

One more key point in this article: a few studies in human “…suggest a potential role of the microbiota in determining optimal vaccine responses in humans.”  They provide a couple of examples:

1. “The relative abundance of several bacterial species in the stool microbiota of 48 Bangladeshi infants have been associated with vaccine-specific IgG and T cell proliferation responses to the oral polio, BCG [tuberculosis], tetanus toxoid, and HBV vaccines.  Increased abundance of Actinobacteria was positively associated with vaccine responses, whereas higher levels of several other species such as Enterobacter, were negatively associated.”
2. “The composition of the infant gut microbiome in infants from rural Ghana was also found to be correlated with rotavirus vaccine responses, where a higher abundance of Bacteroidetes was associated with impaired responses.”

Unfortunately, the few studies done have been done have been small in sample size and as yet, there “… is no human study that demonstrates a causal impact of the microbiota on immune responses to vaccination…”

I did some last minute snooping around and came across an article on Science Daily from 2013:  Gut Bacteria Play Key Role in Vaccination.[iii]  It summarizes two studies that had just been published in PLoS One, out of the University of Maryland, that looked at how biome diversity affected oral vaccine response.  To summarize:  “The scientists found that more diversity in the gut microbiota may enable more robust immune responses to the vaccine.”  Again though, this response was not measured in humans…yet.

To reiterate:  at this point, there is no definitive evidence that the microbiota affect human vaccine response, meaning, whether or not the vaccine is effective in providing immunity, let alone whether or not the bacterial microbiome is at fault in causing adverse vaccine reaction.  What we have right now is nothing more than “the question”:  since the human biome is such an integral part of the immune system, do alterations and/or depletion of the biome affect response – both positive (conferring lifelong immunity) and negative (adverse response and/or lack of immunity) – to vaccines?

 I’m very much looking forward to following this line of research in the future.  Thank you, Keith, for bringing it to my attention.

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[i] Yuan, L, Tsai, PCC, Bell, K.  Do gut microbiota mediate adverse vaccine reaction?  Ann Clin Trials Vaccines Res. 2018:2(2);11-12.

[ii] Lynn, DJ and Pulendran, B. The potential of the  microbiota to influence vaccine responses.  Journal of Leukocyte Biology. 2019:103(2);225-231.  doi: 10.1189/jlb.5MR0617-216R

[iii] https://www.sciencedaily.com/releases/2013/06/130605185931.htm