4. Discussion
dysbiosis, COVID-19 infection, diabetes
DIABETES MELLITUS, COVID-19 INFECTION, DIABETES
To the best of our knowledge, this is the first intervention trial showing that a novel microbiome formula, SIM01, could reduce adverse health outcomes, improve quality of life, and restore gut dysbiosis among elderly subjects and patients with type two diabetes during the COVID-19 pandemic. Using metagenomic sequencing, we demonstrated effective colonisation of probiotic species of SIM01 in the gut. Importantly, SIM01 not only replenished Bifidobacteria but also favoured the coexistence of other beneficial species. On the other hand, we also found that certain detrimental bacteria enriched in COVID-19 or long COVID patients were significantly reduced after receiving SIM01. Overall, our data suggested that SIM01 restored the commensal bacteria and suppressed detrimental pathogens in high-risk populations.The strengths of this study include a rigorous randomised study design with controls that allows a robust evaluation of the modulation impact of the SIM01 formula on reducing the various study outcomes. Predefined endpoints were also used, including a composite of adverse health outcomes which exerted significant impacts on the activities of daily living of the study subjects. In addition, randomisation was conducted at the time of vaccination to minimise the confounding effects of the vaccines on health outcomes. Although ascertainment of these outcomes required subjective evaluation regarding their relationship with the intervention, the study involved only a single, blinded assessor to reduce bias. We also used metagenomic sequencing as objective measures to characterise both the intervention and control groups.One of the reasons for the impaired immune response was due to the depletion of certain beneficial species within their gut microbiota, particularly Observational studies have shown that patients with COVID-19 infection reported altered gut microbiota composition, including reduced bacterial diversity, decreased abundance of short-chain fatty acid-producing bacteria from the Lachnospiraceae, Ruminococcaceae, and Eubacteriaceae families, as well as increased opportunistic pathogens from the Enterobacteriaceae families [Our study had limitations. First, it has been shown that microbiome modifications might be short lived, and further dose-finding studies will be required to examine the optimal dosing and duration of the formula. Second, the duration of follow up lasted for three months only, and continuous observation of these subjects is warranted to assess the sustainability of these beneficial effects. Furthermore, our study requires it to be repeated in other regions as microbiome composition may vary in subjects of different ethnicities. Lastly, the questionnaire items to assess the quality of life were evaluated for face validity only, and the findings should be interpreted with caution.In conclusion, our findings demonstrated a significant role of the novel microbiome formula, SIM01, in reducing adverse health outcomes in elderly subjects and patients with type two diabetes mellitus, which was associated with the restoration of gut dysbiosis. These findings provide significant societal implications for strategies that could protect these vulnerable individuals during the COVID-19 pandemic. We recommend that future research should compare different measurable markers between the SIM01 group and the control group.