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Could baseline gut microbiota and metabolome help predict the durability of immune responses elicited by different COVID-19 vaccines?

In a prospective longitudinal study published in the Journal of Signal Transduction and Targeted Therapy, Researchers characterized the composition of gut microbiota associated with the durability of coronavirus disease 2019 (COVID-19) vaccine-induced immunity.

Additionally, they determined the impact of COVID-19 vaccines on long-term changes in gut microbiota.

To do this, they created two groups made up of people vaccinated with the CoronaVac and BNT162b2 COVID-19 vaccines. They then collected blood and stool samples to analyze their gut microbiome composition, serum antibody levels, and immunological and metabolomic data.

The study’s follow-up lasted more than six months and helped researchers evaluate the two-way interaction between gut microbiome composition and COVID-19 vaccination in both cohorts.

Study: Baseline gut microbiota and metabolome predict long-lasting immunogenicity of SARS-CoV-2 vaccines. Image credit: decor/


Studies have shown that the immunogenicity of COVID-19 vaccines is affected by multiple factors, including the basal composition of the gut microbiome, the gut metabolome, and an individual’s genetics, to name a few.

The authors themselves reported an association between the relative abundance of rosaburia manure and Adolescent Bifidobacterium and vaccine-elicited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels one month after a second dose of BNT162b2 and CoronaVac vaccination.

Likewise, another study by Lunken et al. documented negative correlations between receptor-binding domain (RBD) antibody levels at 12 weeks after the first vaccine dose and total intestinal concentrations of branched-chain fatty acids, isobutyric acid, and isovaleric acid at baseline. .

However, associations between baseline gut metabolome and immune responses to COVID-19 vaccines and how gut microbiome composition affects long-term COVID-19 vaccine-elicited immune protection are unclear.

About the study

In the present study, the investigators recruited healthy subjects aged ≥18 years from two vaccination centers in Hong Kong who received BNT162b2 (north = 121) or the CoronaVac vaccine (north= 40) between April 2021 and June 2021.

They collected their blood samples at baseline (T0), one month after the second dose of the vaccine (post-vaccination, pv) and six months pv.

Participants collected stool samples themselves and sent them to laboratories within 48 hours for deoxyribonucleic acid (DNA) extraction and subsequent analysis.

The researchers subjected plasma from blood samples to serological testing, including the SARS-CoV-2 surrogate virus neutralization test (sVNT) and measurements of cytokines and chemokines.

They presented sVNT levels at six months pv and relative decreases in sVNT levels between one and six months pv. Furthermore, they dichotomized sVNT levels into high and low at six months pv.

The team then subjected DNA from the stool samples to metagenomic and metabolomic analyses. They calculated alpha (and Shannon diversity) and beta (Bray-Curtis dissimilarity) diversity indices, identified gram-positive (+) and gram-negative (-) species according to the criteria specified by the JGI Genome Online Database (GOLD). and calculated the Gram+/Gram- Ratio.

Additionally, the team profiled fecal metabolomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeting 400 metabolites and ten short-chain fatty acids (C2-6) in fecal samples.


Study results showed that gut metabolome and microbiome composition at baseline could help predict SARS-CoV-2 neutralizing antibody (nAb) levels up to six months after receiving two doses of the COVID-19 vaccine. .

In the BNT162b2 group, the authors observed a positive correlation between the initial relative abundances of Feces of Bacillota bifidus, Roseburiaand B. adolescent with sVNT levels at six months pv

Perhaps at 1 month pv, its beneficial functions were masked by the greater immunogenicity of BNT162b2. Note that B. adolescent is a key producer of γ-aminobutyric acid (GABA) in the human intestine.

Furthermore, they observed relative abundances of R. intestinalis and R. faecis The species were positively associated with sVNT levels at six months pv. Therefore, supplementing these bacteria could help overcome the decline in immune responses triggered by BNT162b2.

In the CoronaVac group, the authors observed a correlation between a higher relative abundance of bacteroides and a lower relative abundance of Faecalibacterium prausnitzii at baseline with higher sVNT levels at six months pv

Specifically, a greater relative abundance of D. formicigenerans and lower relative abundances of E. massiliensis and colihominis in those vaccinated with CoronaVac generated higher levels of sVNT at six months pv

Therefore, targeted biotherapeutics colihominis species could help improve the durability of immunity caused by the CoronaVac vaccine.

At the time of enrollment in this study, participants had no history of COVID-19; therefore, its initial gut microbiota signature likely primed CoronaVac recipients for longer-lasting immune responses and did not appear to be related to viral infection.

Thus, fumaric acid, derived from dimethyl fumarate, showed a positive association with long-lasting immunity to BNT162b2 and could exert anti-inflammatory and neuroprotective effects.

Similarly, among CoronaVac vaccinees, fecal tryptophan levels showed a negative association with long-term vaccine immunity.

Another interesting observation was that the abundance of microbial species at one month pv was correlated with long-lasting immunogenicity to CoronaVac but not to BNT162b2. In fact, both vaccines had different mechanisms of action.

Therefore, the gut microbiota of BNT162b2 recipients recovered more rapidly in alpha diversity, but also had a higher proportion of species that did not recover to baseline levels at six months pv. facing CoronaVac recipients (58% vs. 21.6%).

Furthermore, among CoronaVac recipients, reduced gut microbial diversity coincided with markedly decreased gut viral diversity. For the same reasons, vaccine history differentially affected the long-lasting immunogenicity of the BNT162b2 and CoronaVac vaccines.

These findings suggested that alterations in gut microbiota composition due to CoronaVac vaccination mimicked those induced by COVID-19, but not changes related to BNT162b2 vaccination, partly attributable to cross-reactivity with microbial antigens.

CoronaVac is a inactivated vaccine with various viral components as epitopes, while BNT162b2 is a messenger ribonucleic acid (mRNA) vaccine that uses only the spike (S) of SARS-CoV-2 as an epitope.

Decrease and increase in the relative abundance of Bacillota/actinomycetote and Bacteroidota/Pseudomonadotarespectively, were similar in both vaccine groups and corresponded to a reduced Gram+/Gram- ratio pv, indicating intestinal inflammation.

This reduction in the Gram+/Gram- ratio occurred with the depletion of short-chain fatty acids (SCFA) producers. Bacillota species.


In short, greater B. adolescent relative abundance at baseline induced long-lasting immunity to BNT162b2, while a gut microbiota primed by prior vaccination (unrelated to SARS-CoV-2) elicited enhanced immunity to CoronaVac at six months pv

Long-term alterations in gut microbiota due to different COVID-19 vaccines warrant further investigation.

Researchers should also monitor the effects of increasing vaccine doses on gut microbiota composition, recovery, and long-term health in recipients of different COVID-19 vaccines.

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