Probiotics and COVID-19.

We read with interest Joyce Mak and colleagues' Correspondence in The Lancet Gastroenterology & Hepatology on the role of probiotics in illnesses related to COVID-19. Although we largely agree with the authors' conclusions, we believe that use of probiotics in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has wider implications.

SARS-CoV-2 has been postulated to affect gut inflammation both directly and indirectly, infecting intestinal epithelial cells through the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2, and inducing pro-inflammatory chemokine and cytokine release.2, 3 Recent studies suggest that SARS-CoV-2 instigates an acute intestinal inflammatory response, highlighted in laboratory tests by elevated levels of faecal calprotectin and serum interleukin-6, and clinically evidenced by diarrhoea.

Although gastrointestinal disorders are frequent in COVID-19, nothing is known regarding the ability of SARS-CoV-2 to affect the host microbial flora. However, previous studies have shown that ACE2 expressed in the intestinal epithelium regulates the ecology of the gut microbiome through intestinal amino acid homoeostasis and that ACE2 receptors are markedly downregulated by the entry of SARS-CoV-2 into cells through membrane fusion. The intestinal downregulation of ACE2 can consequently lead to an altered microbiota that confers susceptibility to inflammation of the gut.4, 5, 6 Moreover, other coronaviruses, such as the porcine epidemic diarrhoea virus, are able to directly cause microbial dysbiosis, with decreases in the proportion of beneficial bacteria and increases in harmful bacteria.

Given this evidence, bacteriotherapy could represent a complementary resource for the prevention and restoration of SARS-CoV-2 intestinal mucosa damage through the modulation of gut microbiota and decreasing related inflammation. In other infections, such as HIV, in which intestinal inflammation and related microbiota impairment can affect gut epithelial barrier function, bacteriotherapy (through microbiota surface compounds and metabolites) has been shown to inhibit apoptosis, regulate signalling pathways to produce cytokines, maintain intestinal epithelial homoeostasis, and allow recovery of gut mucosal health, thereby attenuating inflammation.8, 9 We believe that studies of bacteriotherapy in SARS-CoV-2 are needed to evaluate the potential effects on intestinal mucosal inflammation and microbiome homoeostasis.

Finally, products available for bacteriotherapy are not the same and have different potential effects. Thus, the conclusions of each study must be considered separately, and the results of meta-analyses that collate data obtained from studies done with different products can be misleading.