Can the gut microbiota help improve vaccine efficacy?

In theory, vaccines work on a simple (or fairly simple) principle: they train our immune system (composed of an army of antibodies) to react quickly to attacks by invading pathogens. (sidenote: To do this, a harmless fragment of the invader is inoculated into the host so that it develops targeted defenses. When the real pathogen subsequently appears, our defenses are ready to neutralize it.  https://www.who.int/news-room/feature-stories/detail/how-do-vaccines-work ) However, in practice, vaccines do not always work. They save millions of lives each year, especially among young children who are more vulnerable to infectious disease, but they are more effective in European children than in children from low- and middle-income countries (LMIC). Although treated with vaccines, many of these children fail to develop protective immunity. (sidenote: While nearly 100% of Finnish children develop protective immunity in response to rotavirus vaccines, this is the case for only 58% of children in Nicaragua and 46% of children in Bangladesh. Similarly, protection rates for the BCG vaccine range from 0%-51% in African children versus 88%-100% in European children. ) In other words, the army of antibodies that makes up their immune system (sidenote: Innate and adaptive immunity  The human body protects itself using two kinds of defense mechanisms: innate immunity and adaptive immunity. Innate immunity is the first line of defense against disease agents and is an immediate response, while adaptive immunity is delayed but provides lasting protection Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Principles of innate and adaptive immunity. ) fails to respond. Untrained to recognize and eradicate the enemy, they are unlikely to be able to defend the host in a real battle. But what causes this “immune inequality”?

Gut microbiota, an ally of immune response

The answer may involve a special third force allied with the immune army, the gut microbiota. The development and functioning of the gut microbiota and immune system are intimately linked; but the gut microbiota of European children differs significantly from that of children from LMIC. The researchers thus believe that differences in microbiota composition may explain variations in vaccine response. Accordingly, certain studies have sought to modify the gut microbiota in order to improve immune response. Trials in humans that used probiotics (live bacteria that strengthen the microbiota) to increase the proportion of patients who develop protective immunity have shown positive outcomes in half of cases. Two sentries of the gut microbiota, the bacterial genera Bifidobacterium (sidenote: Bifidobacterium A genus of Y-shaped bacteria, most species of which are beneficial to humans. They are found in the gut of humans, and in some yogurts.

They:
- Protect the gut barrier 
- Participate in the development of the immune system and help fight inflammation 
- Promote digestion and improve symptoms of gastrointestinal disorders Sung V, D'Amico F, Cabana MD, et al. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018 Jan;141(1):e20171811.  O'Callaghan A, van Sinderen D. Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Front Microbiol. 2016 Jun 15;7:925. Ruiz L, Delgado S, Ruas-Madiedo P, et al. Bifidobacteria and Their Molecular Communication with the Immune System. Front Microbiol. 2017 Dec 4;8:2345. ) and Bacteroides, seem particularly capable of rallying the immune system’s troops.

Improving vaccine response

Although further research is required, the researchers are already considering new vaccine strategies that involve the modulation of gut flora composition in the hope of stimulating responses to vaccines. This new approach may increase access to effective vaccines in low- and middle-income countries (LMIC). It may also make it possible to do without certain adjuvants that are added to boost immune responses, but which are thought to have adverse side effects that fuel vaccine hesitancy.