Gut microbiota may influence COVID-19 vaccine efficacy and safety

Modulation of gut microbiota may help enhance efficacy and reduce side effects of coronavirus disease 2019 (COVID-19) vaccines, preliminary data from the Chinese University of Hong Kong (CUHK) have shown.

Blood samples from 10 individuals (age, 33–83 years; female, 60 percent) showed an almost 50 percent increase in proportion of B cells and 15–80 percent decreases in concentrations of inflammatory cytokines following COVID-19 vaccination in individuals who took a microbiome immunity formula for up to 2 months prior to vaccination (n=4), compared with those who did not take the formula (n=6).

The four participants had been taking a CUHK-developed microbiome immunity formula daily prior to receiving the mRNA COVID-19 vaccine (40 percent) or inactivated COVID-19 vaccine (60 percent).

“Most participants had received one dose of COVID-19 vaccine between January and March 2021,” said Professor Siew-Chien Ng of the Centre for Gut Microbiota Research, CUHK. “Several participants had hypertension, while one had diabetes.”

“The preliminary study in our laboratory also showed higher post-vaccination levels of immunoglobulin G [IgG] and IgM antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] in participants who took the microbiome immunity formula before vaccination,” Ng reported.

Based on these preliminary findings, the CUHK researchers will conduct a randomized controlled trial to evaluate the effect of the microbiome immunity formula on the efficacy and safety of COVID-19 vaccines in 500 individuals with diabetes or ≥65 years of age – populations that are at increased risk of gut dysbiosis.

“The participants will be randomized to take the microbiome immunity formula or placebo for 3 months, and followed up for 1 year. There will be no limitation on the type of COVID-19 vaccine they choose to receive,” said Dr Joyce Mak of the Department of Medicine and Therapeutics, CUHK.

“The gut microbiota influences immune response to vaccination,” said Professor Francis Chan of the Centre for Gut Microbiota Research, CUHK. [Front Microbiol 2019;10:1305; Nat Rev Immunol 2017;17:219-232] “Dysbiosis of gut commensals have been suggested to contribute to adverse reactions to COVID-19 vaccines.” [BMJ 2021;doi:https://doi.org/10.1136/bmj.n149] 

For example, dominance of a Bacteroides-driven enterotype has been found in the gut microbiome of individuals with high intakes of protein and animal fat. Some genera of Bacteroidetes stimulate secretion of proinflammatory cytokines and neurotoxins, resulting in aberrant immune responses that contribute to abnormal inflammatory reactions to COVID-19 vaccines due to cytokine storms. [BMJ 2021;doi:https://doi.org/10.1136/bmj.n149] 

“Rectifying gut microbiome dysbiosis with oral supplementation of prebiotics and probiotics during vaccination has been suggested as a solution for managing adverse reactions induced by COVID-19 vaccines,” said Chan. [BMJ 2021;doi:https://doi.org/10.1136/bmj.n149] 

In previous studies, gut microbiota was found to play a role in immune response to influenza vaccination. [Immunity 2014;41:478-492; Cell 2019;178:1313-1328.e13; Curr Opin Virol 2019;37:16-25] Another study showed significantly higher plasma levels of influenza vaccine–specific IgG following supplementation of probiotics vs placebo. [Br J Nutr 2012;107:876-884]