Image credit: “Petri dishes with cultures of bacteria grown on agar jelly.” by M. J. Richardson is under a CC BY-SA 2.0 License.
This post was reviewed by Dr. Brett Finlay, one of our subject matter experts.
This study was conducted by researchers from The Chinese University of Hong Kong.
The paper we’ll be demystifying can be found here, if you’d like to follow along!
TL;DR: Researchers examined differences between the microbiomes of SARS-CoV-2 patients, pneumonia patients, and healthy individuals. They found lasting changes to the fecal microbiome, with an increase in pathogenic bacteria and a decrease in beneficial bacteria. Many species were correlated with severity and viral load in SARS-CoV-2 patients.
You can’t define a human being without defining the human microbiome; after all, microbes make up more than half of our total cell count. These bacteria, fungi, and archaea can shape our health in a huge variety of ways. While there are more obvious connections such as gut health and nutrition, the microbiome also effects the incidence and progression of diseases like asthma, obesity, and Parkinson’s.
Being so influential, it makes sense that the opposite also occurs. Changes in lifestyle, environment, and health can all change the content of the microbiome. Cooperating with your microbiome can in turn improve your own health. However, a shock to the system like SARS-CoV-2 could throw both you and your microbial partners for a loop.
Researchers from The Chinese University of Hong Kong tackled this question with a study involving 15 hospital patients confirmed to have SARS-CoV-2 infection. They also used an equal number of healthy individuals as healthy controls, and 6 pneumonia patients as controls with similar symptoms. Other researchers had already found evidence of inflammatory responses in the gut of SARS-COV-2 patients, which contains the highest numbers of microbes. ACE2, the receptor of which is vital for SARS-CoV-2 infection, is also known to be important in the gut microbiome and intestinal inflammation.
Their methods were not for the easily squeamish. Stool samples from the SARS-COV-2 patients were taken 2-3 times per week until they were discharged from the hospital. These types of samples provide an excellent window into the state of the microbiome, as they are incredibly rich in microbes. Viral load of these samples was measured by RT-PCR, a technique which quantifies the amount of the viral genetic material, or RNA, present in a sample. For more on how RT-PCR works, check out this previous article.
To find the microbial content, the researchers looked at DNA, the genetic material of microorganisms. Due to DNA being unique between each species, they were able to not only find the types of bacteria present, but also the population levels of each, using a technique named metagenomics. Unlike more selective approaches, like 16S RNA sequencing, which copies out a specific section of a genome, metagenomics can give the holistic picture of microbial content that this study required.
They began by comparing the bacterial population of samples from SARS-COV-2 patients with the two controls. In SARS-COV-2 patients who hadn’t received antibiotics, there were higher levels of pathogenic bacteria such as Clostridium hathewayi, Actinomyces viscosus, and Bacteroides nordii. These three have been known to enter the bloodstream in a process known as bacteremia. The SARS-COV-2 patients that received antibiotics had lower levels of helpful bacteria that assist immunity, such as Faecalibacterium prausnitzii and Ruminococcus obeum. In fact, these levels were extremely low in SARS-COV-2 regardless of their exposure to antibiotics, even after symptoms and viral load cleared up, indicating lasting changes.
The researchers followed up on this by examining the overall population of the microbiome after recovery. While the microbiome of 5 of the SARS-COV-2 patients began to return to the healthy configuration, another 5 patients diverged further from normality. By the end of the study, these 10 patients continued to have markedly different microbial communities.
Next, the team investigated if there was a correlation between a patient’s microbiome and the severity of their SARS-COV-2 infection, using a sample of 7 SARS-COV-2 patients that hadn’t received any antibiotic treatment. Of the 23 types of bacteria related to severity, 15 of them were from the phylum Firmicutes. This lines up with a mouse study that found Firmicutes influences gut expression of ACE2. On a lighter note, Firmicutes also causes fermented drinks like beer and wine to spoil.
Image credit: “Bacillus subtilis Gram” by Y tambe is under a CC BY-SA 3.0 License.
Of the Firmicutes members implicated in severity, three that rose significantly were of particular interest. Coprobacillus bacterium increases ACE2 expression in the mouse colon; the other two, Clostridium ramosum and C. hathewayi, are linked to bacteremia. Additionally, two important species in the Firmicutes phylum fell in number: Alistipes onderdonkii helped to break down amino acids and maintain the immune response in the gut, and Faecalibacterium prausnitzii lowered inflammation.
The final aspects compared were the levels of SARS-CoV-2 in the samples relative to bacterial levels. 14 species were correlated with viral load, with 6 of these were from the Bacteroidetes phylum, with 4 known for lowering ACE2 expression in the mouse colon. This could indicate that the Bacteroidetes help to protect us against SARS-COV-2 infection by disrupting the virus’ means of entry. On the other hand, one of the Firmicutes, Erysipelotrichaceae, was strongly correlated with high viral load. Due to its implicated role is gastrointestinal inflammation, this species of bacteria could be working with SARS-CoV-2 to aid in infection.
It’s important to note that this study can’t designate these bacteria to any concrete role in defending or exacerbating SARS-COV-2 in patients. All that can be gathered are possible roles based on prior knowledge and bacteria populations. More importantly, this study has a low sample size of only 15 with a small timeframe of sampling. While it’s fascinating that a mostly respiratory disease can cause such profound changes to the digestive tract, this may be due to pre-existing gastrointestinal problems in such a small group, instead of gastrointestinal ACE2 directly interacting with SARS-CoV-2. To get a better idea of changes in the general microbiome over time, a longer-term study with a larger number of patients is required.
This team from Chinese University of Hong Kong have laid the groundwork for examining a new angle of looking at SARS-COV-2. Tapping into the microbiome could open new means of treatment or prevention, depending on the findings of future studies.
Take care of yourselves out there, both you and your microbes.
