‘Important implications’ for COVID-19 vaccines: Review shows gut microbiota affects various vaccine efficacy
This could be because the gut microbiota plays an important role in modulating B cell and T cell responses; both of which are important in producing immune responses.
With infants as an example, it was found that an abundance of Bifidobacterium in their faecal microbiota is significantly associated with CD4+ T cell responses and antibody responses to non-orally administered vaccines.
CD4+ T cells are said to be the “orchestrators, regulators, and direct effectors” of antiviral immunity and could help generate stronger and longer-lived antibody responses.
A higher diversity of the microbiota in infants, on the other hand, was associated with poorer responses to vaccination.
The above observations were seen in studies comparing the efficacy of oral poliovirus vaccine in infants from China and Ghana.
Writing in the Nature Reviews Immunology, researchers from the South Australian Health and Medical Research Institute and Stanford University School of Medicine said there has been more evidence showing that the gut microbiota is “an important and targetable factor influencing the baseline immune status and the response to vaccination”.
They analysed several existing clinical cohort studies, interventional studies, and animal models and derived at this conclusion.
Consisting of microbiota composition, microbial metabolites, antibiotics, probiotics and prebiotics, the gut microbiota is highly variable amongst different individuals over the course of life.
Evidence from clinical cohort studies
In China, a study of oral poliovirus vaccine in over 100 infants found that the relative abundance of Bifidobacteria in the faecal microbiota was correlated with increased poliovirus-specific IgA responses.
Although another study in India did not yield similar findings, both studies showed that a higher diversity of the microbiota was associated with poorer responses to vaccination.
Effects of antibiotics
The researchers also found that antibiotic intake during early infancy can affect the gut microbiota and in turn, the efficacy of vaccines.
For example, a randomised controlled trial in India found that infants administered with the antibiotic azithromycin did not show improvement in vaccine immunogenicity. Poor immunogenicity is related to poorer vaccine efficacy.
Antibiotics intake also reduced the efficacy of vaccines in adults, but in some studies, the effect was not immediate.
One study found that there was no immediate significant difference in the anti-rotavirus lgA responses in adults who were randomised to take a cocktail of broad-spectrum antibiotics or only the antibiotic vancomycin 36 hours before receiving an oral rotavirus vaccine.
However, by day seven after vaccination, it was found that adults who took only the antibiotic vancomycin, had anti-rotavirus lgA responses that were at least two times greater than adults who took several other antibiotics.
Notably, adults who produced a greater lgA response to the vaccination had an increased ratio of Enterobacteriaceae to Bacteroides species. This was also seen in the faecal microbiota of Ghana infants who had better response to the oral rotavirus vaccination.
“Taken together, these results suggest that antibiotic-driven changes to the gut microbiota can induce major changes in the metabolome, alter inflammatory responses and impair antibody responses to vaccination.
“In summary, interventional studies carried out so far suggest that antibiotic-driven changes to the gut microbiota can influence responses to influenza vaccination and possibly to oral rotavirus vaccines, although all of the studies are limited by a small sample size and by the fact that antibiotics were typically administered shortly before immunization,” said the researchers.
Probiotics the solution?
Existing studies showed mixed results on whether probiotic supplementation could improve vaccine efficacy.
A number of trials on pre/probiotic supplementation involving the elderly found no or little improvement in their responses to influenza vaccine.
A recent systematic review also showed that only about half of the 26 randomised controlled trials studied showed that probiotics had a beneficial impact on vaccine response.
However, the researchers also pointed out that the trials had only small sample sizes.
Moreover, none of the trials specifically recruited participants with a disrupted microbiota. Therefore, the researchers said it would be highly unlikely that administering probiotics to participants with well-colonised, healthy gut, would cause their immune system to produce significant responses to vaccinations.
In addition, trials assessing the link between pre/probiotic supplementation and vaccine efficacy in the elderly mostly used probiotics containing the Lactobacillus strains, which are not commonly found in the adult gut, the researchers highlighted.
“Further research is needed to identify adult-adapted strains of probiotics that might be more beneficial as interventions in the elderly.”
In conclusion, the researchers said that existing interventional studies on the impact of probiotics or antibiotics on vaccine responses have been “significantly underpowered” and have provided evidence for “only relatively modest effects” of the microbiota on vaccine response.
Source: Nature Reviews Immunology
Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms.
https://doi.org/10.1038/s41577-021-00554-7
Authors: Lynn, D.J., Benson, S.C., Lynn, M.A. et al.
