This is a quick post on the current COVID-19 pandemic. For those of you who still have unanswered questions about COVID-19, I highly recommend listening to a podcast interview with Dr. Eric Feigl-Ding. You can listen to the interview here. Dr. Ding is an epidemiologist at the Harvard Chan School of Public Health, a Senior Fellow at the Federation of American Scientists and an advisor to the World Health Organization.

The number one cause of death from the novel coronavirus is due to oxygen deprivation caused by pneumonia. Approximately 20% of those who are infected with this virus may develop a life-threatening form of pneumonia that requires being intubated and placed on a ventilator. From what we know of cases in China, the average length of time on a ventilator is four weeks. This makes ICU turnover very slow and will cause a huge burden on the health-care system. Given the finite number of ventilators currently available, many nations will soon face what Italy is facing by deciding who will or will not be saved.

For that reason, I want to link to several papers about the gut-lung axis and the importance of our microbiome in preventing secondary pneumonia infections. All of these papers are open access and can be downloaded in full at the links provided.

The first is an opinion paper published in 2016 titled Emerging pathogenic links between microbiota and the gut–lung axis. It’s fairly easy to read so I encourage all of you to download and share a copy.

As this paper makes clear,

“The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut–lung axis. Although the gut–lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.”

Furthermore:

“The gut microbiota is broadly protective against respiratory infection, as its depletion or absence in mice leads to impaired immune responses and worsens outcomes following bacterial or viral respiratory infection. Administration of SFB [segmented filamentous bacteria] improved resistance to Staphylococcus aureus pneumonia and Bifidobacterium spp. protected against both bacterial and viral pulmonary infection in mice. Lactobacillus spp. and Bifidobacterium spp.-based probiotics also improved the incidence and outcomes of respiratory infections in humans.”

One hypothesis for how this is done involves granulocyte–macrophage colony-stimulating factor or GM-CSF. This is how a 2017 paper described the mechanism:

“The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte–macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling. Increased pulmonary GM-CSF production in response to infection is primed by the microbiota through interleukin-17A. By combining models of commensal colonization in antibiotic-treated and germ-free mice, using cultured commensals from the Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla, we found that potent Nod-like receptor-stimulating bacteria in the upper airway (Staphylococcus aureus and Staphylococcus epidermidis) and intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens) promote resistance to lung infection through Nod2 and GM-CSF. Our data reveal the identity, location, and properties of bacteria within the microbiota that regulate lung immunity, and delineate the host signaling axis they activate to protect against respiratory infection.”

Further confirmation of the importance of gut flora to lung immunity was recently published in a paper titled Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production:

“Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.”

Please note that while the last two papers dealt with a bacterial pneumonia model, there is nothing to suggest that the same would not be true for viral pneumonia.

So now, more than ever, healthy gut flora may make the difference between being in the 80% of cases that are mild to moderate should you be unlucky enough to be infected with COVID-19 as opposed to the 20% of cases who go on to require intensive hospitalization. The fact that the unwell elderly, smokers, those with high blood pressure, type-2 diabetics, the obese and those with cardiovascular issues are most at risk suggests to me that pre-existing gut dysbiosis (and resulting endotoxemia and chronic immune activation) is at the heart of this unfortunate 20% cohort.

Therefore, I strongly advise my readers to begin taking prebiotics and probiotics twice daily to build up your colonies of healthy gut flora. The prebiotic I currently recommend is Jarrow Formulas Inulin FOS. As for a probiotic, I’m currently recommending Hyperbiotics Pro-15 because they are made by the same manufacturer that used to make my probiotic. Both are available for sale on Amazon.

Other recommendations include ceasing all smoking and vaping, and yes that includes marijuana. Smoking, and to a lesser extent vaping, alter oral flora which in turn alters gut flora for the worse. In fact, anything that irritates lung tissue like air pollution or wood fires should be avoided. Refrain from binge drinking alcohol as that will only lower your immunity and contribute to gut dysbiosis as detailed here. And it should go without saying that you must eat a healthy diet and get plenty of rest to keep your immune system in good shape.

Obviously none of this will prevent you from being infected if you come in contact with someone shedding coronavirus. Only social distancing can do that at this time. So please do us all a favor and self-isolate as much as you can so we can prevent overwhelming our health care providers. But should you become infected, current research strongly suggests that having a healthy gut flora is far more advantageous than not.

Stay safe everyone!

 

 

 

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