Probiotic Potential in a Pandemic

Armoring up against COVID-19 with beneficial bacteria

By Ana Santos, Neuroscience PhD student

Humans are no strangers to microbes and the world is grappling with one that has taken center stage, SARS-CoV-2. Commonly known as COVID-19, this actor is new on the scene and highly viral, making prevention and treatment difficult. COVID-19 is diverse in its acting techniques, a spectrum ranging from mildly cold-like or no symptoms, to
severe organ damage or death, with lots of variation in between. Interestingly, severe cases seem to be associated with more symptoms like diarrhea, vomiting, nausea, loss of appetite, bloody feces, and gut pain[1] and little is known yet about longer term effects.
​
​Most germs we interact with are friends and not foes. The gut microbiota is like a director, staging the immune system to be strong, and managing the good microbes to ward off pathogens. The current theater production is set in the gut and lungs (called the gut-lung axis), which foreshadows how dysfunction in one organ can influence the other. Here, we feature the immune system as the star of the play and cast probiotic microbes as supporting characters.

Terminology
Viral : Ability of a virus to infect, cause disease and spread from host to host.
Microbiota: Collection of microbes: bacteria, viruses, fungi, etc., specific to gut and lungs.
Leaky Gut: Increased permeability of the gut barrier, can contribute to cytokine storm by increasing viral & bacterial invasion into circulation and promoting inflammation.
Dysbiosis: General term for a microbiome characterized by
increases in pathogens and loss of beneficial bacteria. Promotes
inflammation and leaky gut.
Cytokine Storm: Release of many proinflammatory signals (cytokines). When prolonged it causes damage to cells and organs.
Genera, Species, & Strain:
The order that the tree of life categorizes organisms into groups starting from general shared genera to specific unique strains.

As the lead role, the immune system’s purpose is to kill the virus, but like superheroes who destroy the city in their epic battles, the immune system can leave a wreckage of damaged cells and tissues in its effort to fight off the villain, COVID-19.
This can lead to a sequel of persistent symptoms in the gut and lungs even after the infection has been resolved [2]. Early reports have found that COVID-19 infection is linked with a leaky gut and dysbiosis which promote gut inflammation [1]. A gut-lung axis implies signaling goes both ways between the lungs and gut. While the majority of our bodies’ immune cells reside in our gut, they don’t necessarily stay there, so gut inflammation can reach the lungs and vice versa, fueling a fire that is already occurring [3].

Enter left stage, friendly bacteria to help ‘boost’ the immune system. Probiotics are live microorganisms that provide a health benefit when enough are consumed. The most common bacterial genera used in products are Lactobacilli and Bifidobacterium, which are also beneficial members of our normal lung and gut microbiota. The term probiotic is actually very broad. When making conclusions about the influence of these actors, it really comes down to the specific species and strain of the bacteria and the amount needed to induce specific health effects [3].

General mechanisms of probiotics relevant to COVID-19 include [3]:

• Boosting anti-inflammatory cytokines, like interferons that ‘interfere’ with viruses
• Producing anti-viral substances to kill and prevent virus infection
• Supporting the gut barrier, reducing leaky gut
• Limiting dysbiosis by out-competing pathogens

Probiotic bacteria are dynamic in their actions and mechanisms; they don’t replace our microbes, but interact with the microbes already there to alter their host. It has been shown that certain probiotics influence the gut-lung axis, preventing infection, reducing severity and length of other viral lung infections [3]. Additionally, improving the body’s anti-viral response can reduce the stress of infection and organ damage.

Stress is a catch-all term, including emotional or social stress like isolation, and physical stressors such as infection or disrupted sleep. Extreme and/or accumulating stressors, like many have experienced through the pandemic, can significantly impact our health and also induce dysbiosis, making us more susceptible to infection. This highlights another role probiotics may play, as certain probiotics help buffer the effects of stress and reduce symptoms of anxiety and depression [4]. This is especially important for an aging population who are the most vulnerable to severe COVID-19 infections and the negative effects of stress. Except in certain cases (like severely immunocompromised patients), probiotics are generally safe and well tolerated even in intensive care settings (ICU) and vulnerable populations, like the elderly. Probiotics have been shown to prevent ventilator-associated pneumonia in patients in the ICU, and ventilator support is necessary when individuals with COVID-19 have severe respiratory distress [3]. Therefore, the idea of preventatively boosting our defenses to help reduce the severity of COVID-19 infection is highly attractive.

---

The virality of COVID-19 requires researchers to be creative in their treatment methods. However, a script for treatment and prevention may not lie in killing the virus. Remembering that COVID-19 enters our cells by binding spike proteins at our ACE2 receptors, blocking this mechanism may essentially stop the virus from entering cells and replicating in the first place. 

There are drugs that bind to this receptor and block COVID-19 from doing so; however, blocking the ACE2 receptor can also lead to a pro-inflammatory response [2]. So what is to be done about this paradox? Well, microbes are not easily outshined. One specific cast member, Lactobacillus plantarum, produces chemicals called plantaricins. These products can actually bind to COVID-19’s spike proteins, preventing the virus from binding to ACE2 without blocking the receptor and negatively impacting the immune system [5], an exciting twist in this story! When we understand probiotic mechanisms, it highlights the potential for more bacteria to be screened for the production of substances that could neutralize COVID-19 and combat infection.

Stagehands are often overlooked, like the natural probiotics occurring in fermented foods. Common ferments include yogurt, fermented vegetables, sour cream, some cheeses, kefir, kombucha, sourdough bread and of course, beer and wine. Lactobacillus plantarum is even found in cabbage ferments like sauerkraut and kimchi. There are many species of microbes in varying amounts within these products, but they are readily accessible and when eaten regularly are believed to promote a healthy gut. You can hear more about fermented foods and health here [3].

There are still gaps in our knowledge about probiotics, and it is strongly encouraged that individuals listen to their gut (pun intended). Some symptoms are mild (and gassy) but tend to go away with continued use. However, if a probiotic causes an adverse reaction, like significant gut distress, know that personal response trumps any other suggestions. 

In addition, the market for probiotics is admittedly a mixed bag; some products are properly evaluated in controlled human studies, while others have unsubstantiated claims or are poorly manufactured. Others are simply too expensive, costing from $0.50 - $4/dose. While people can review online whether specific brands test their product’s quality in a lab, there are also websites to help consumers make informed choices by performing independent lab-based evaluation of products on the market such as: Lab Door, Consumer Health Report, and Consumer Lab Report (not free).

A housekeeping note: while probiotic therapies may contribute to viral protection, the suggestions in this post draw from currently available clinical studies on probiotic bacteria and other viral respiratory tract infections, not COVID-19. This information is in no way meant to replace advice or treatments from medical doctors.

Although the curtains have closed on this post, the potential of probiotics to boost our health is information we can use in this pandemic and beyond. But as we continue to deal with COVID-19 and the accompanying isolation, at least with trillions of microbes we are never truly alone.
 
Podcast link on the science of fermented food

References:

1. Zuo T, Liu Q, Zhang F, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021; 70(2):276-284. doi:10.1136/gutjnl-2020-322294 
2. Behl T, Kaur I, Bungau S, et al. The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions. Life Sci. 2020; 257:118075. doi:10.1016/j.lfs.2020.118075 
3. Olaimat AN, Aolymat I, Al-Holy M, et al. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. Nat Part J Sci Food. 2020; 4:17. doi:10.1038/s41538-020-00078-9 
4. Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019; 102:13-23. doi:10.1016/j.neubiorev.2019.03.023. 
5. Anwar F, Altayb HN, Al-Abbasi FA, Al-Malki AL, Kamal MA, Kumar V. Antiviral effects of probiotic metabolites on COVID-19. J Biomol Struct Dyn. 2020; 1-10. doi:10.1080/07391102.2020.1775123