"Gut Microbiota's Role in Predicting Long-term Immune Responses to COVID-19 Vaccines"

In a prospective longitudinal study recently published in the Journal of Signal Transduction and Targeted Therapy, researchers explored the potential relationship between baseline gut microbiota and the immune responses triggered by COVID-19 vaccines. The study also aimed to investigate how COVID-19 vaccines might affect long-term changes in the gut microbiota.

Background: Prior research has demonstrated that various factors, including an individual’s baseline gut microbiome composition, gut metabolome, and genetics, can influence the effectiveness of COVID-19 vaccines. Some earlier studies have suggested associations between specific gut bacteria and antibody levels following COVID-19 vaccination. However, it remains unclear how the baseline gut metabolome influences immune responses to COVID-19 vaccines and how the composition of the gut microbiome affects long-term vaccine-induced immunity.

Study Details: For this study, researchers recruited healthy individuals aged 18 and older who received either the BNT162b2 or the CoronaVac COVID-19 vaccine between April and June 2021 in Hong Kong. They collected blood samples at three time points: at baseline (T0), one month after the second vaccine dose (post-vaccination or p.v.), and six months p.v. Participants also provided stool samples within 48 hours of collection for DNA extraction and analysis.

Blood samples were subjected to serological tests, including the SARS-CoV-2 surrogate virus neutralization test (sVNT), as well as cytokine and chemokine measurements. The researchers examined sVNT levels at six months p.v. and changes in these levels between one and six months p.v.

DNA extracted from stool samples was analyzed using metagenomic and metabolomic techniques. This analysis included computing alpha and beta diversity indices, identifying Gram-positive and Gram-negative species, and calculating the Gram+/Gram− ratio. Additionally, stool metabolomes were profiled using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to target 400 metabolites and ten short-chain fatty acids in fecal samples.

Results: The study found that the composition of the gut metabolome and microbiome at baseline could predict levels of neutralizing antibodies against SARS-CoV-2 up to six months after individuals received two doses of a COVID-19 vaccine.

In the BNT162b2 vaccine group, there was a positive correlation between the baseline relative abundances of specific bacteria (e.g., Bacillota bifidum, Roseburia faecis, and B. adolescentis) and sVNT levels at six months p.v. These bacteria may play a role in immune responses to the vaccine.

Conversely, in the CoronaVac vaccine group, a higher relative abundance of Bacteroides and lower relative abundances of Faecalibacterium prausnitzii at baseline were correlated with higher sVNT levels at six months p.v.

The study also found that microbial species present in the gut one month p.v. were correlated with long-lasting immune responses to CoronaVac but not BNT162b2. The recovery of gut microbiota diversity was faster in BNT162b2 recipients, but some species did not return to baseline levels at six months p.v.

Furthermore, the gut microbiota changes induced by CoronaVac vaccination resembled those seen in individuals who had contracted COVID-19, while the changes differed from those associated with BNT162b2 vaccination.

Conclusions: To summarize, the study suggests that the composition of the gut microbiome and metabolome at baseline can influence the durability of immune responses to COVID-19 vaccines. Specifically, certain bacteria at baseline were associated with higher antibody levels following vaccination.

These findings highlight the need for further research into the long-term effects of different COVID-19 vaccines on gut microbiota. Additionally, it is important to monitor how changes in vaccine dosing might impact gut microbiota composition and overall recipient health, particularly as more data becomes available.