Published on in Vaccine Update for Healthcare Providers
The term “holobiont,” originally coined by Lynn Margulis, is increasingly used to describe organisms by taking into account not only the host but also their associated microbiome (Sherwin, 2019). Indeed, people have more commensal bacteria living on the surface of their bodies than they have cells in their bodies. And as the potential impact of this co-existence continues to be explored, it is becoming increasingly clear that these bacteria are not just along for the ride.
What health conditions are related to the microbiome?
The types of bacteria living in an individual’s intestine have effects throughout the body, including on the immune system, heart, brain and metabolism. Indeed, even our sense of smell has been found to be influenced by the bacteria living in our intestines. Health conditions including obesity, cardiovascular disease, and some socially based conditions, such as autism, have been correlated with the types of bacteria found in the intestine. Likewise, immune responses to treatments for HIV and cancer, as well as preventive measures, like vaccines, have been correlated with the microbiome.
What do we know about intestinal microbiota and health?
The precise mechanisms for several of these observations have not been worked out to date; therefore, we should consider these findings to be correlated, but not necessarily causal. Some observations are worth noting:
- Dysbiosis, the loss of microbial diversity, can be caused by antibiotics. While some types of bacteria return within a few weeks, other types may not reappear even six months after completion of the antibiotic regimen. Therefore, antibiotics may have effects beyond treating a primary infection.
- Babies born by caesarian section tend to have less diverse microbiota in the first few weeks of life compared with those born vaginally; however, the former tend to gain biodiversity within the first six weeks of life.
- Immune responses in the intestine tend to account for the resident bacteria; however, in some cases, a chronic low-grade inflammation can occur. Conditions like Crohn’s disease or ulcerative colitis, can result from the chronic inflammation.
- As people age, the likelihood of experiencing chronic low-grade inflammation increases; this is referred to as “inflammaging.”
A closer look at vaccines, immunity and the intestinal microbiome
A perspective article by Bali Pulendran in the Nov. 29, 2019, issue of Science, called “Immunology taught by vaccines,” was particularly interesting for its consideration of immunity to vaccination as related to the microbiome.
Pulendran described how differences in vaccine efficacy have been found when vaccines are evaluated in different countries, citing examples of lower efficacy against rotavirus and oral polio vaccines in some low- and middle-income countries. While acknowledging a variety of potential reasons for these observations, including environmental differences, parasitic infections, nutrition, and conditions affecting the intestine, such as tropical enteropathy, the author also entertained the potential role of diverse microbiomes.
In particular, Pulendran considered findings by Oh and colleagues, “TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination,” published in Immunity (2014). Following a study of immune responses generated in people immunized with trivalent influenza vaccine (TIV, Nakaya, 2011), Oh and colleagues used a mouse model to further evaluate a suggested role for Toll-like receptor 5 (TLR5). TLR5 is a component of the innate immune system that recognizes bacterial flagellin, the main protein found in the flagellum, or tail, of bacteria. When stimulated, TLR5 leads to an inflammatory immune response. Because TIV protects against a virus, the activation of a receptor associated with bacterial infection was of interest.
In a series of elegant experiments, Oh and colleagues found that stimulation of TLR5 early after vaccination was associated with stronger and more durable antibody responses against TIV, but TLR5 was not stimulated directly by components in the vaccine. To better understand whether the microbiome played a role in what they were observing, the researchers treated mice with antibiotics and found that when the microbiome was depleted, so, too, were antibody responses to TIV. Hypothesizing that the bacterial components were acting as adjuvants, the team tested a few additional vaccines, which supported this hypothesis. Specifically, responses to inactivated polio vaccine, another inactivated, non-adjuvanted vaccine, were diminished, but responses to a live, viral vaccine for yellow fever and two inactivated, alum-adjuvanted vaccines, Tdap and an HIV envelope protein, were not affected.
Pointing out that not all data support the findings of Oh and colleagues, Pulendran made the point that this idea is still important to consider from a public health perspective, particularly when related to antibiotic use.
So, what does this mean from a clinical standpoint?
Takeaway 1: Prescribe antibiotics judiciously.
We already understand the importance of antibiotic resistance, but if the microbiome also plays a role in immunologic responses to vaccines, or pathogens encountered in nature, we have even more reason to limit prescriptions.
Takeaway 2: Educate about risks and benefits.
While we are used to thinking about risks and benefits in the practice of medicine, often parents and the public are not. If they or a loved one are sick, they want to feel as though they are “doing something,” which often means requesting a prescription. It is important to educate parents and the public regularly about the risks and benefits of any action, so that when someone is sick, the framework for discussing risks and benefits is in place.
Takeaway 3: Consider the “holobiont.”
When treating patients, don’t just consider the potential effects on other body systems, also consider its effects on the microbiome, and whether that could mean anything for your patient’s health.
Resources and selected references
To find out more, check these additional resources:
- Margulis L. Symbiosis in Cell Evolution: Microbial Communities in the Archean and Proterozoic Eons. 2nd ed. W.H. Freeman and Co., New York,1993.
- Zilber-Rosenberg I, Rosenberg E. Role of microorganisms in the evolution of animals and plants: The hologenome theory of evolution. FEMS Microbiol Rev. 2008 Aug;32(5):723-735.
- Rosenberg E, Zilber-Rosenberg I. The hologenome concept of evolution after 10 years. Microbiome. 2018 Apr 25;6(1)78. doi:10.1186/s40168-018-0457-9
Microbiome and disease
- Forkosh E, Ilan Y. The heart-gut axis: New target for atherosclerosis and congestive heart failure therapy. Open Heart. 2019 Apr 23;6(1):e000993. doi:10.1136/openhrt-2018-000993
- Pulendran B. Immunology taught by vaccines. Science. 2019 Nov 29;366(6489):1074-1075.
- Sherwin E, Bordenstein SR, Quinn JL, et al. Microbiota and the social brain. Science. 2019 Nov 1;366(6465). doi: 10.1126/science.aar2016
Systems biology and vaccines
- Gaucher D, Therrien R, Kettaf N, et al. Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J Exp. Med. 2008 Dec 22;205(13):3119-3131.
- Querec TD, Akondy RS, Lee EK, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009 Jan;10(1):116-125.
- Nakaya HI, Wrammert J, Lee EK, et al. Systems biology of seasonal influenza vaccination in humans. Nat Immunol. 2012 Jul 10;12(8):786-795.
- Oh JZ, Ravindran R, Chassaing B, et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccine. Immunity. 2014 Sep 18;41(3):478-492.
Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.
You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. You should not use it to replace any relationship with a physician or other qualified healthcare professional. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult your physician or, in serious cases, seek immediate assistance from emergency personnel.