Article Summary
There is evidence on the microbiotas’ impact on the effectiveness of vaccines, suggesting a direct link between a high diversity of gut microbiota and a more reasonable response to vaccination. It is comprehended that HIV infection reduces the richness and diversity of the gut microbial population and depletes some of the genera associated with anti-inflammatory conditions. In addition, microbiota composition can predict immune status in HIV infection (Pastor-Ibáñez, 2021). However, the prospect of using transcriptomics and metagenomics as surrogate markers of vaccine response is not thoroughly researched. Therefore, the Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine objective is to correlate mRNA expression profiles. Moreover, it aims to evaluate the effect of gut microbiome profiles that may predict VL control after ATI in participants who received a DC-based HIV-1 vaccine trial.
Materials and Methods
All materials and tools used in the article have been certified and are reliable. All patients were with chronic HIV-1 infection, older than 18, with a baseline CD4+ T-cell count greater than 450 cells/mm3, a nadir CD4+ T-cell count more than 350 mm3 undetectable plasma VL levels (Pastor-Ibáñez, 2021). BMCs were gathered from study participants 1 week before each vaccine dose was administered. Monocytes were sequestered from them and incubated with granulocyte-macrophage colony-stimulating factor and interleukin to induce cells in MDDC that were manipulated for vaccine production. Patients were divided into responders and nonresponders based on the VL factor. Total RNA was isolated from 5 × 106 frozen monocytes removed from PBMC; they underwent quality control, then pooled into equimolar mixtures (Pastor-Ibáñez, 2021). Finally, the DNA sequence of each cluster on flow cells was determined using cycles of Sequencing-By-Synthesis technology.
The number of amplicon sequence variants was collapsed to the bacterial phylum and genus level using the GreenGenes database to assess the abundance of genera. As applicable, distinctions between groups were evaluated using multiple Mann-Whitney-Wilcoxon or Kruskal-Wallis tests with Bonferroni correction. Two separate approaches were also operated to examine the effects of the intervention between the vaccine and placebo groups, these being time point comparisons and estimates of mathematical changes between the groups. The microbiome samples were clustered by genus composition using nonmetric multivariate scaling based on environmental distance matrices calculated by Bray-Curtis dissimilarity and implemented in packages (Pastor-Ibáñez, 2021). To reach the articles aim, the normalized numbers of phylotypes were multiplied by the corresponding set of gene numbers estimated for each taxon to determine the gene content.
Results
The results revealed that no differential gene expression was detected in patients before or after vaccination compared with the placebo group, regardless of the cutoff for change multiplicity applied. Therefore, it can be suggested that the DC vaccine did not affect blood transcriptomes (Pastor-Ibáñez, 2021). The gut microbiota composition between baseline and postvaccine data was examined by LEfSe analysis, which revealed no differences in bacterial composition between the vaccine and control groups. These outcomes indicated that the DC vaccine did not affect the gut microbiota’s richness, diversity, or design.
The TSUT microbiota was analyzed using the relative abundance rates obtained at the phylum and genus levels. Responders showed enriched Bacteroides, Prevotella, Oribacterium, Methanosphaera, Bulleidia, Akkermansia, and Butyrivibrio. In contrast, according to Pastor-Ibáñez (2021), nonresponders had elevated Phascolarctobacterium, Mogibacterium, and Collinsella. PICRUSt2 analysis to predict the metagenomic functional content of the gut microbiota revealed significant differences between the responding and nonresponding groups at the KEGG III level. In particular, the predicted amino acid metabolic pathway for short-chain fatty acid production was significantly increased in responders.
Discussion
Although the transcriptomic regulation of the biological processes during HIV infection has been studied, much remains unclear. HIV-1 infection leads to a host immune response that is qualitatively and quantitatively distinct from other viral infections. The DC-based therapeutic vaccine induced a major transcriptomic shift in recipients by five weeks, unchanged after ATI and subsequent viral relapse. Vaccination-induced modifications in the gut bacteriome were also detected. This may reflect the remoteness of the lymph node from the gut and the short follow-up period after vaccination. Therefore, intranodal administration of the DC vaccine did not affect the composition of the core bacterial populations in the present study (Pastor-Ibáñez, 2021). Although the vaccine did not appear to affect BMC transcriptomes or the gut microbiome, both omics showed an appropriate association with the VL response after ATI.
Furthermore, the results underscore the importance of IFN pathways in the control of HIV, supporting studies claiming that HIV infection triggers IFN responses in acute conditions and contributes to the power of HIV replication. Evaluation of predicted metabolic functions revealed that several functional amino acid metabolic pathways were increased in respondents. Among these were fermentation of L-lysine to acetate and butanoate, degradation of ethyl malonyl-CoA, and degradation of L-tyrosine (Pastor-Ibáñez, 2021). These three pathways can produce SCFA, directly or indirectly, as acetate, acetoacetate, and butyrate. The end products of microbial fermentation, SCFAs, have been described as critical metabolites in the regulation of intestinal permeability and intestinal inflammation. It has also been investigated that SCFAs can be degraded to acetoacetate via β-oxidation in mitochondria.
In conclusion, there were no results indicating any effect of the DC vaccine on BMP transcriptomes and the gut microbiota in the present study. An alternative analysis revealed that responders who had more time to viral relapse had enrichment of genes related to the IFN type I signaling pathway and were involved in the host defense response. In addition, the gut microbiota of responders was more diverse, and more associated with metabolic SCFA production than nonresponders.
Reference
Pastor-Ibáñez, R., Díez-Fuertes, F., Sánchez-Palomino, S., Alcamí, J., Plana, M., Torrents, D., Leal, L.,and García, F. (2021). Impact of transcriptome and gut microbiome on the response of HIV-1 infected individuals to a dendritic cell-based HIV therapeutic vaccine. Vaccines, 9(7), 694.