News & Views: Considering Intestinal Microbiota in Practice
Published on in Vaccine Update for Healthcare Providers
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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.
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.
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:
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?
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.
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.
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.
To find out more, check these additional resources:
Contributed by: Charlotte A. Moser, MS, Paul A. Offit, MD
Categories: Vaccine Update January 2020, News and Views About Vaccines
Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.
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