Modulation of Gut Microbiota to Enhance Health and Immunity

Not Applicable

Active, not recruiting

Interventions: Dietary Supplement: Microbiome immunity formula
Dietary Supplement: Active placebo

Brief Summary: The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is now a pandemic and has culminated major morbidity and mortality globally. Studies have shown that patients with underlying type 2 diabetes mellitus (DM), obesity, old age and hypertension had a higher risk of developing severe COVID-19 infection and mortality related to COVID-19.Emerging evidence has shown that gut microbiota plays an important role in the pathogenesis of COVID-19.

Detailed Description: HYPOTHESIS We hypothesize that modulating the gut microbiota with a microbiome immunity formula can rebalance the gut microbiota in populations at risk of infection, like, patients with type 2 DM and elderlies and can lower the number of hospitalisation and reduce side effects associated with COVID-19 vaccination.

AIM We aim to evaluate the efficacy of modulating gut microbiota with a microbiome immunity formula in vulnerable subjects (patients with underlying type 2 DM and elderlies) in improving immune functions, reducing adverse events associated with COVID-19 vaccinations and reducing hospitalisation in susceptible individuals during the COVID-19 pandemic.

STUDY DESIGN This is a double-blinded, randomized, active-placebo controlled study comparing a microbiome immunity formula and placebo in enhancing immunity and reducing hospitalisation within one year. Except two kinds of subjects (Substudy 1: Patients with Type 2 DM and Substudy 2: Elderly individual) will be included in respective substudy, all other methodologies are the same. In each substudy, at least half of the recruited subjects will plan to receive COVID-19 vaccination and start to take the study products after vaccination. Recruited subjects will be randomised to receive a microbiome immunity formula or active placebo for 3 months, with another 9 months follow-up after completion of study products.

Recruitment & Eligibility

Inclusion Criteria

Age 18 years - below 65 years
A confirmed diagnosis of type 2 DM for ≥ 3 months with stable control (i.e. no change in DM medications in recent 2 months)
Written informed consents obtained

Exclusion Criteria

Known history of confirmed COVID-19 infection
Known active sepsis or active malignancy
Known increased infection risk due to underlying immunosuppressed state which includes:
- Prior organ or hematopoietic stem cell transplant
- Neutropenia with absolute neutrophil count (ANC) <500 cells/ul at the time of study inclusion
- Known HIV infection with CD4 <200 cells/ul at the time of study inclusion
- On concomitant immunosuppressants or corticosteroid at a dose of prednisolone equivalent dose 10mg or more for more than 3 months
Known history or active infective endocarditis
On peritoneal dialysis or haemodialysis
Documented pregnancy

Substudy 2

Inclusion Criteria:

Exclusion Criteria:

Known history of confirmed COVID-19 infection
Known active sepsis or active malignancy
Known increased infection risk due to underlying immunosuppressed state which includes:
- Prior organ or hematopoietic stem cell transplant
- Neutropenia with absolute neutrophil count (ANC) <500 cells/ul at the time of study inclusion
- Known HIV infection with CD4 <200 cells/ul at the time of study inclusion
- On concomitant immunosuppressants, chemotherapies or corticosteroid at a dose of prednisolone equivalent dose 10mg or more for more than 3 months
Known history or active infective endocarditis
On peritoneal dialysis or haemodialysis
Known active malignancy
Known terminal illness with life expectancy less than 3 months

Arm && Interventions

Group	Intervention	Description
Active arm	Microbiome immunity formula	Subject will be instructed to take microbiome immunity formula 2 sachets daily for a total of 12 weeks.
Placebo arm	Active placebo	Subject will be instructed to take active placebo daily for a total of 12 weeks.

Primary Outcome Measures

Name	Time	Method
Adverse events/Serious adverse events	within 6 months	Proportion of patients who presented with new symptoms/diseases which exerted unfavourable impacts on subjects. Serious adverse events are those adverse clinical events that resulted in hospital admission and/or death

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of the COVID-19 vaccine	3 months and 6 months	Measured by serum neutralization assay against pseudo virus and live virus, and IgM and IgG against receptor-binding domain \[RBD\] and S1
Change in gut microbiome	1, 3, 6, and 12 months	Measured the gut microbiome changes by metagenomic sequencing and metabolite profiling by targeted and/or untargeted metabolites profiling
Changes in plasma inflammatory cytokines	3 months and 6 months	Measured the inflammatory cytokines (CRP or ESR) in blood result
Restoration of gut dysbiosis	1, 3, 6 and 12 months	It is defined as improvement in (i) gut microbiome composition and diversity; (ii) functional potential (i.e., MetaCyc pathway abundances); and (iii) proliferation of beneficial bacteria genus (i.e., bifidobacteria, eubacterium, roseburia and other short-chain fatty acids producers
Number of unscheduled hospitalisation and clinic visits	1, 3, 6, and 12 months	Number of unscheduled hospitalisation and clinic visits
Changes of quality of life	1, 3, 6, and 12 months	Measured the score of EQ-5D-5L which measure the health-related quality of life
Changes in glycaemic control	1, 6 and 12 months	Measured by HbA1c