Probiotics and COVID-19 – Authors' reply
Authors: Joyce W Y Mak, Francis K L Chan, Siew C Ng
Journal: The Lancet. Gastroenterology & hepatology (2020)

We thank Eric Giannoni and colleagues and Giancarlo Ceccarelli and colleagues for their comments on our Correspondence.1Mak JWY Chan FKL Ng SC Probiotics and COVID-19: one size does not fit all.Lancet Gastroenterol Hepatol. 2020; 5: 644-645Summary Full Text Full Text PDF PubMed Scopus (134) Google Scholar New data have since highlighted that patients with COVID-19 have an altered gut microbiome with depletion of beneficial commensals (Eubacterium ventriosum, Faecalibacterium prausnitzii, Roseburia and Lachnospiraceae taxa) and enrichment of opportunistic pathogens (Clostridium hathewayi, Actinomyces viscosus, Bacteroides nordii) during hospitalisation.2Zuo T Zhang F Lui GCY et al.Alterations in gut microbiota of patients with COVID-19 during time of hospitalization.Gastroenterology. 2020; (available online May 20.)DOI: 10.1053/j.gastro.2020.05.048Google Scholar Importantly, gut microbiome configuration was associated with COVID-19 disease severity, and altered gut microbiota persisted even after clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suggesting that the virus might inflict prolonged harm to human microbiome homoeostasis.2Zuo T Zhang F Lui GCY et al.Alterations in gut microbiota of patients with COVID-19 during time of hospitalization.Gastroenterology. 2020; (available online May 20.)DOI: 10.1053/j.gastro.2020.05.048Google Scholar Other risk factors for severe COVID-19, including old age, obesity, and diabetes mellitus,3Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death.BMJ. 2020; 368m1198Crossref PubMed Scopus (1107) Google Scholar have been shown to be associated with gut dysbiosis, which might contribute to the poor prognosis of COVID-19.4Qin J Li Y Cai Z et al.A metagenome-wide association study of gut microbiota in type 2 diabetes.Nature. 2012; 490: 55-60Crossref PubMed Scopus (4731) Google Scholar During this crucial moment, with more than 6 million confirmed cases of COVID-19 globally, we understand that the situation is desperate, and it is not uncommon to try all alternative measures. In the absence of a vaccine or effective therapy for COVID-19, we agree that probiotics represent a complementary approach for the prevention and restoration of SARS-CoV-2-induced mucosal damage or inflammation through the modulation of gut microbiota. Probiotics exert their beneficial effects through several different mechanisms, and substantial differences appear to exist between different probiotic bacterial species and strains. Organisms therefore need to be selected in a rational manner to treat different diseases.5Ng SC Hart AL Kamm MA Stagg AJ Knight SC Mechanisms of action of probiotics: recent advances.Inflamm Bowel Dis. 2009; 15: 300-310Crossref PubMed Scopus (460) Google Scholar Currently, questions remain concerning which patients should receive probiotics, what is the best way to deliver probiotics, how to ensure optimal delivery, and whether there is variation in efficacy among different populations. As the world waits in semi-lockdown mode, continued scientific progress for COVID-19 prevention or treatment is highly important, and probiotics represent one option. We call for robust and well planned studies that can facilitate the identification of probiotic strains, including both well documented probiotics and novel COVID-19-specific probiotics, that might result in reduced susceptibility to COVID-19 or less severe disease. JWYM reports grants from Janssen, the Hong Kong College of Physicians, and the Hong Kong Society of Gastroenterology, outside the submitted work. FKLC reports grants from Olympus Hong Kong and China, Pfizer, AstraZeneca, Takeda Pharmaceuticals, Takeda (China) Holdings, and Given Imaging, and personal fees from the American Gastroenterological Association, Medical Association of Guangdong Province, Olympus Hong Kong and China, Pfizer, AstraZeneca, Takeda Pharmaceuticals, EA Pharma, Takeda (China) Holdings, Associação dos Médicos Hospitalares da Função Pública de Macau, Pfizer Upjohn Korea, Fujifilm, Ministry of Health Singapore, and Japanese Gastroenterological Endoscopy Society. FKLC is also an advisor and commentator for evidence-based medicine for the Ministry of Health of the People's Republic of China, Pfizer, AstraZeneca, Ministry of Health Singapore, American College of Physicians Journal Club, and Nature Reviews Gastroenterology & Hepatology, outside the submitted work. SCN reports grants from Ferring and personal fees from Takeda, AbbVie, Janssen, and Tillotts, outside the submitted work. Probiotics and COVID-19: one size does not fit allAs of April 20, 2020, coronavirus disease 2019 (COVID-19) has affected more than 2 million people globally. In February, 2020, China's National Health Commission and National Administration of Traditional Chinese Medicine suggested the use of probiotics in patients with severe COVID-19.1 We reviewed the evidence for the role of probiotics in COVID-19-related illnesses (appendix). Full-Text PDF Probiotics and COVID-19We read with interest Joyce Mak and colleagues' Correspondence1 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. Full-Text PDF Probiotics and COVID-19We appreciate the interest in probiotics to assist with the management of COVID-19 in Joyce Mak and colleagues' recent Correspondence1 in The Lancet Gastroenterology & Hepatology, but we would like to propose a more balanced and optimistic view on this topic. Further to our recent review,2 we feel that physicians now appreciate that although COVID-19 is mainly a respiratory disease, the gut can act as a reservoir for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).3 Citing meta-analyses of randomised trials that investigate the effect of probiotics on preventing respiratory tract infections, Mak and colleagues conclude that probiotics have a "modest efficacy". Full-Text PDF