Gut Lung Microbiota Axis: Scope of Probiotics in COVID-19 infections

It has been reported that COVID-19 virus is related to a group of SARS-like coronaviruses, with 89.1% nucleotide similarity. 2 This structural similarity is particularly noted in the domains binding to the angiotensin-converting enzyme-2 (ACE2) host receptor 3 - which are largely expressed in the epithelium of not just the lungs, but also the liver and intestine. Specifically, the expression of ACE2 receptor has also been identified on the luminal surface of differentiated epithelial cells located in the small intestine, colon and crypt cells 4

It is noteworthy that ACE2 mutants exhibit altered gut microbial composition, and patients who are affected with respiratory infections, including COVID-19, may generally have alterations in gut microbial flora, which in turn has led researchers to establish an interaction between COVID-19 to the gut microbiota 5

The involvement of gastrointestinal milieu in COVID-19 also sought substance through a series of small case series bringing out that certain infected patients had an altered gut microbiota composition, with depletion in bacterial species of Lactobacillus and Bifidobacterium. 6

Notably, gut–lung axis - the crosstalk between intestinal tract and lungs, involves continuous bidirectional communication via the blood system, which helps to modulate the local immunity of both; gut and lungs, as well as their respective microbial patterns and composition. 7 Since the role of microbiota is to maintain homeostasis and regulate local immune responses, it is quite logical to expect that microbial alteration, known as dysbiosis, could contribute to the onset of disease. 8

In a study conducted in 206 patients with low severity COVID-19 brought out interesting findings indicating the presence of a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to possess a longer delay before viral clearance, and to experience a delay in diagnosis compared to patients who had only respiratory symptoms 9

Probiotics along with higher intake of dietary fibre may constitute a valuable supportive medical treatment, promoting anti-inflammatory effects and augmenting immune response. Specifically, these modalities can be adopted in asymptomatic patients and patients with mild symptoms or in quarantine who can follow their own diet in order to prevent and reduce systemic inflammation and improve alveolar-capillary function and lung permeability. In addition, this strategy could be potentially considered in the acute phase of COVID-19 to prevent worsening of pulmonary interstitial lesions and to mitigate post-infection complications, including fibrotic outcomes 1

There is certainly acceptable scientific data with the use of various Lactobacillus strains in improving outcomes in respiratory infections. Studies have indicated that Lactobacillus based species helps to decrease the incidence of laboratory-confirmed respiratory viral infections in elderly individuals 10

A recent clinical trial which used a combination of multi-strain probiotics including Lactobacillus administered to hospitalised patients positive for COVID-19, resulted in an eightfold lower risk of developing respiratory failure compared to standard care, thus significantly improving clinical outcomes in COVID-19 infections 11

In conclusion, the most common therapeutic options for viral infections are directed at either blocking viral entry and replication or promoting durable cellular and humoral immunity for the uninfected population via vaccination. Since there is no vaccine or unanimously established clinically proven therapies available at this time, manipulation of microbial patterns through the use of probiotics may help to reduce cell inflammation, maintain a healthy gut microbial diversity and help strengthen the immune system. 1

Adapted from:

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2 Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579: 265–269.

3 Lu R, Zhao X, Li J, et al. Genomic characterisation, and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395: 565–574

4 Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012; 487: 477–481

5 Gao QY, Chen YX and Fang JY. 2019 novel coronavirus infection and gastrointestinal tract. J Dig Dis 2020; 21: 125–126. DOI: 10.1111/1751- 2980.12851.

6 Mak JWY, Chan FKL and Ng SC. Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol. Epub ahead of print 24 April 2020. DOI:10.1016/S2468-1253(20)30122-9.

7 Tulic MK, Piche T and Verhasselt V. Lung gut crosstalk: evidence, mechanisms, and implications for the mucosal inflammatory diseases. Clin Exp Allergy 2016; 46: 519–528.

8 Trompette A, Gollwitzer ES, Yadava K, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 2014; 20: 159–166

9 Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients with Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. 2020;115(6):916-923. doi:10.14309/ajg.0000000000000664

10 Wang B, Hylwka T, Smieja M, Surrette M, Bowdish DME, Loeb M. Probiotics to Prevent Respiratory Infections in Nursing Homes: A Pilot Randomized Controlled Trial. J Am Geriatr Soc. 2018;66(7):1346-1352. doi:10.1111/jgs.15396

11 d'Ettorre G, Ceccarelli G et al, (2020) Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19. Front. Med. 7:389. doi: 10.3389/fmed.2020.003