PMID- 35170078 OWN - NLM STAT- MEDLINE DCOM- 20220511 LR - 20220716 IS - 1440-1746 (Electronic) IS - 0815-9319 (Print) IS - 0815-9319 (Linking) VI - 37 IP - 5 DP - 2022 May TI - Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study. PG - 823-831 LID - 10.1111/jgh.15796 [doi] AB - BACKGROUND AND AIM: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS: Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-alpha), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS: This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients. CI - (c) 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Zhang, Lin AU - Zhang L AUID- ORCID: 0000-0003-1634-3780 AD - Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Xu, Zhilu AU - Xu Z AUID- ORCID: 0000-0002-5552-7534 AD - Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Mak, Joyce W Y AU - Mak JWY AUID- ORCID: 0000-0001-5221-7349 AD - Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Chow, Kai Ming AU - Chow KM AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Lui, Grace AU - Lui G AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Li, Timothy C M AU - Li TCM AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Wong, Chun Kwok AU - Wong CK AD - Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Chan, Paul K S AU - Chan PKS AUID- ORCID: 0000-0002-6360-4608 AD - Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Ching, Jessica Y L AU - Ching JYL AUID- ORCID: 0000-0001-8257-2843 AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Fujiwara, Yasuhiro AU - Fujiwara Y AD - Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. FAU - Chan, Francis K L AU - Chan FKL AUID- ORCID: 0000-0001-7388-2436 AD - Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Ng, Siew C AU - Ng SC AUID- ORCID: 0000-0002-6850-4454 AD - Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. LA - eng GR - The DH Chen Foundation/ PT - Journal Article DEP - 20220302 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Immunoglobulin G) SB - IM MH - Bacteria MH - *COVID-19/therapy MH - Dysbiosis MH - *Gastrointestinal Microbiome MH - Humans MH - Immunoglobulin G MH - Pilot Projects MH - SARS-CoV-2 MH - *Synbiotics PMC - PMC9115073 OTO - NOTNLM OT - SARS-CoV-2 OT - immunity OT - microbiota OT - probiotics EDAT- 2022/02/17 06:00 MHDA- 2022/05/12 06:00 PMCR- 2022/03/02 CRDT- 2022/02/16 05:52 PHST- 2022/01/18 00:00 [revised] PHST- 2021/08/13 00:00 [received] PHST- 2022/02/03 00:00 [accepted] PHST- 2022/02/17 06:00 [pubmed] PHST- 2022/05/12 06:00 [medline] PHST- 2022/02/16 05:52 [entrez] PHST- 2022/03/02 00:00 [pmc-release] AID - JGH15796 [pii] AID - 10.1111/jgh.15796 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2022 May;37(5):823-831. doi: 10.1111/jgh.15796. Epub 2022 Mar 2.