Written by Gregory Govoni and Caroline McMahon
A healthy and diverse microbiome is important for many biological processes, including protection against pathogen colonization. This relationship between the gut microbiome and the immune response triggered by an infection has widespread implications, potentially leading to undesired disease outcomes.
How do respiratory pathogens affect the microbiome?
There is growing evidence that the respiratory tract and gut microbiotas can help regulate the body’s response to invading respiratory viruses, while in a similar fashion, invading respiratory viruses can induce immune responses that alter the composition of the microbiota. Frequently, the microbiota stimulate the immune system in such a way that limits or diminishes the respiratory virus infection as discussed in Ichinohe et al. However, it appears that is not always the case, since some microorganisms have been shown by DE Lastours et al. to increase viral replication in the respiratory tract.
According to Sencio et al. antiviral immune responses induced by respiratory pathogens, such as the influenza virus, can affect susceptibility to secondary infections by changing the microbial composition of the respiratory and gastrointestinal tracts. The resulting dysbiosis (loss of diversity), can alter host immune responses and allow bacterial pathogens to proliferate. For example, a 2010 publication by Shieh et al. showed that in the 2009 H1N1 pandemic, ~30% of cases were accompanied by a bacterial co-infection despite administration of antibiotics.
While many of the research findings about viral respiratory pathogens in general are likely to apply in the case of SARS-CoV-2, the theories need to be verified and modified. For instance, early studies, as described in Zhou et al. indicate similar co-infection rates for SARS-CoV-2 and influenza H1N1; however, the morbidity rate associated with co-infection with SARS-CoV-2 is much higher.
What technology is available for microbiome analysis?
Researching variation in disease susceptibility and outcome among individuals could be due to differences in their microbiota, which can be evaluated by several methods. Most of these methods rely on massively parallel high-throughput sequencing technologies to sequence a phylogenetically unique gene (usually the 16S ribosomal RNA (rRNA) gene) or random sequencing of all genes present at sampling site, and can be challenging since skilled library preparation and data analysis is required.
Recent advances have made it possible to perform microbiome profiling using fragment analysis by capillary electrophoresis (CE). inBiome, based in the Netherlands, utilizes fragment-analysis-based technology to identify microbial signatures associated with different disease phenotypes. Compared to next-generation sequencing (NGS), a fragment analysis–based approach performed on a CE instrument has a much shorter turnaround time (<5 hours per run). It also enables scaling to meet demand, has a relatively low per-sample cost, and does not require a skilled bioinformatician.
Using fragment analysis–based technology to identify microbial signatures associated with SARS-CoV-2 infection
Understanding the origin of person-to-person variability once infected by SARS-CoV-2 virus is an area of intense research. Evidence concerning other respiratory pathogens suggests that the pharyngeal microbiota may play a role.
Using that previous research as a foundation, inBiome used fragment analysis-based technology to identify pharyngeal microbiota signatures associated with the presence or absence of SARS-CoV-2 on a total of 46 positive and 89 negative samples. They found a signature in the pharyngeal microbiota samples associated with a two-fold lower SARS-CoV-2 positivity rate compared to all other profiles. Results of the 2020 study by Budding A et al. imply an association between pharyngeal microbiota, age, and the presence of SARS-CoV-2. Additional follow-up studies are needed to establish a causal relationship between microbiota and SARS-CoV-2 susceptibility.
The benefits of a diverse microbiota
Microbiota populations in the nose, throat, lungs, and gut have important influences on several disease outcomes, including respiratory infections. Evidence indicates more diverse microbiota are better able to prevent respiratory pathogens from colonizing the lungs while specific microbes have been shown to stimulate pro-inflammatory responses, which lead to more severe disease outcomes. Being able to detect and analyze the composition of these microbiota in research is vital to our understanding of disease outcomes, especially when it comes to critical diseases such as COVID-19.
Read the paper
- Budding A et al. (2020) “An Age Dependent Pharyngeal Microbiota Signature Associated with SARS-CoV-2 Infection.” Available at SSRN: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3582780
For Research Use Only. Not for use in diagnostic procedures