Gut microbial taxa trigger unique immune signaling pathways to combat viruses such as SARS-CoV-2 but the mechanisms are poorly understood. However, it is thought that alterations to the relative abundance of particular taxa within the gut, namely those that offer anti-viral immunity, play a critical role to future vaccine research success and susceptibility to infection. Disentangling the mechanisms driven by these taxa could be the key to developing a cure for potential solution for the SARS-CoV-2 virus.
Outnumbering our cells by ten to one, our gut microbiome plays a critical role in the modulation of our overall health. Specifically, during development and throughout our lives, the gut signals immune response to disease, infection, and vaccines. Across the globe, the microbiome varies highly by age, diet, environmental conditions and socioeconomic status. Due to the high variability of these factors and limited vaccination success in particular global populations, there is a need to understand how microbial disturbance or dysbiosis can affect human health, vaccine response and susceptibility to infection. In addition to the relative abundance of the gut microbiome altering immunomodulatory signaling pathways, studies illustrate that low diversity of the gut microbiome dampens immune response. However, the exact mechanisms of these phenomena are not fully understood.
To better address correlations between the microbiome and our immune system, next generation sequencing (NGS) has been utilized as a powerful research tool to evaluate the causal mechanisms of immune response related to changes in microbial relative abundance. NGS is advantageous as it is high throughput and culture independent allowing for a comprehensive snapshot of the microbial community under various biological conditions. By sequencing the microbiome in conjunction of metabolomic expression, researchers can better disentangle the mechanisms of dysbiosis and inference with immunoregulatory pathways allowing for more targeted vaccines research across global populations where microbiomes and environmental factors may vary.
In recent reviews, researchers synthesized data from experiments and clinical trials to demonstrate how alterations in gut microbiome relative abundance modulates viral vaccine immune response. The reviews illustrate that the relative abundance of particular commensal and probiotic gut bacteria are responsible for eliciting an antiviral response and act as a vaccine adjuvant within the Lactobacillus and Bifidobacterium genuses. Findings show that a low Firmicutes to Bacteroides ratio causes impaired immunity after vaccination as those microbes act as relative abundance mediated adjuvants triggering production of immune cells and antibodies via cell signaling pathways. As most vaccines are given early in human development, the early successional microbial taxa (facultative anaerobes) are very critical to the success of many vaccines research and development. Particularly, microbe localization and network interactions influence immune response, which is very dependent on nutritional availability and distribution. Particular focus of future research will hopefully tackle optimal microbial species, doses and timing of administration of these probiotics or key beneficial microbes.
In addition to poor anti-viral and vaccine responses, low abundance of key taxa can result in opportunistic infection by bacteria already present in the body. In a recent research paper, use of NGS showed translocation of gut microbes such as Bacteroides to the lung after sepsis, which resulted in a dominant relative abundance of gut microbes in the lung. Alteration of the relative abundance in turn triggered increased systemic inflammatory immunoregulatory factors. Again, by investigating how changes in relative abundance of particular taxa modifies immune signaling pathways, this enables more potential future vaccination and treatment development options that are more viable for infections such as SARS-CoV-2 across global populations.
Despite the plentiful data available from experiments and clinical trials, there is still a need to understand the causal relationships between microbial composition and vaccines as well as viruses. Utilizing targeted NGS with the new Ion AmpliSeq Microbiome Health Research Kit, we can characterize many key microbial species mentioned in the literature, particularly 73 gut microbial species, including all anti-viral and vaccine adjuvant taxa, allowing us to monitor changes in relative abundance and link this data to variation in immunoregulatory pathways. The kit is fully comprehensive with a highly sensitive workflow that utilizes eight of the nine hypervariable 16S rRNA gene regions to accurately detect microbial shifts impacting vaccine efficacy and antiviral immune responses. With better understanding of the causal relationships of microbially mediated anti-viral immunity and their underlying mechanisms, we can make more precise understanding of future treatment development options when finding a solution to SARS-CoV-2.
For more information on the latest microbiome panels for human research, please go to thermofisher.com/ngsmicrobiome.
Read the paper:
Vlasova AN, Takanashi S, Miyazaki A, Rajashekara G and Saif LJ. How the gut microbiome regulates host immune responses to viral vaccines. Current Opinion in Virology. 01 June 2019. https://doi.org/10.1016/j.coviro.2019.05.001
Ciabattini A, Olivieri R, Lazzeri E, and Medaglini D, Role of the Microbiota in the Modulation of Vaccine Immune Responses. Front. Microbiol., 03 July 2019. https://doi.org/10.3389/fmicb.2019.01305
Dickson RP, Singer BH, Newstead MW, Falkowski NR, Erb-Downward JR, Standiford TJ, and Huffnagle GB, Enrichment of the Lung Microbiome with Gut Bacteria in Sepsis and the Acute Respiratory Distress Syndrome. Nat Microbiol.; 1(10): 16113. https://doi.org/10.1038/nmicrobiol.2016.113