Gut microbiota–derived synbiotic formula hastens COVID-19

A novel gut microbiota–derived synbiotic formula known as SIM01 is an effective adjuvant therapy for coronavirus disease 2019 (COVID-19), which hastens antibody formation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reduces nasopharyngeal viral load, reduces proinflammatory immune markers, and restores gut dysbiosis in COVID-19 patients, researchers from the Chinese University of Hong Kong (CUHK) have reported.

“Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting gut dysbiosis will improve outcomes of COVID-19 is unknown,” noted the researchers. “We aimed to evaluate the efficacy of SIM01 as an adjuvant therapy in terms of immunologic responses and gut microbiota changes among patients hospitalized for COVID-19.”

In the open-label pilot study, 35 hospitalized patients with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and given standard treatment for COVID-19. Twenty-five patients also received SIM01 (median age, 50 years; male, 56 percent) as adjuvant therapy for COVID-19 for 28 days, while 10 patients who did not receive SIM01 (median age, 46.5 years; male, 30 percent) acted as controls. Blood and faecal samples were collected at baseline and at weeks 2, 4 and 5. [J Gastroenterol Hepatol 2022;doi:10.1111/jgh.15796]

Results showed that significantly more patients receiving SIM01 than controls developed immunoglobulin G (IgG) antibody against SARS-CoV-2 (88.0 percent vs 63.3 percent; p=0.037) by day 16. Only one patient (4.0 percent) and eight patients (26.7 percent) in the SIM01 group and control group, respectively, failed to develop IgG antibody upon discharge. In addition, a significant negative correlation with nasopharyngeal SARS-CoV-2 viral load was seen in the SIM01 group over time (R=0.2900; p=0.0005), but not in the control group (R=0.0082; p=0.95).

Levels of proinflammatory immune markers, including plasma interleukin (IL)-6, IL-1RA, monocyte chemoattractant protein (MCP-1), macrophage colony-stimulating factor (M-CSF), and tumour necrosis factor (TNF)-α, decreased significantly in the SIM01 group at week 5 (all p<0.05), but not in the control group (all p>0.05). “This supports our hypothesis that treatment with SIM01 has a potent anti-inflammatory effect in hospitalized COVID-19 patients,” noted the researchers. “Measurement of plasma proinflammatory cytokines has clinical significance as COVID-19 patients often suffer from the consequence of cytokine storm, which leads to severe multiorgan damage.”

Using shotgun metagenomics sequencing, the relative abundance of probiotic species in the SIM01 group was shown to be higher than the control group (p=0.044). In addition, the abundance of beneficial bacterial species depleted in COVID-19 patients significantly increased (p<0.01 vs baseline) and the abundance of pathogenic bacterial species enriched in COVID-19 patients significantly decreased (p<0.01 vs baseline) by weeks 4 and 5 in the SIM01 group. Notably, no such changes were observed in the control group, suggesting an essential role of SIM01 in restoring gut dysbiosis in COVID-19 patients.

“For the first time, we have shown that a novel combination of probiotics could enhance antibody formation in patients with COVID-19 … which provided further evidence that modulation of gut microbiota can improve host immune function against COVID-19,” the researchers concluded. “Further mechanistic studies will be important to elucidate the importance of individual bacteria species in SIM01, the optimal duration of treatment, and the magnitude of colonization in the gut necessary for the reported benefits.”