Gut microbiome modulation reduces infections, shows other health benefits

A gut microbiota–derived synbiotic formula developed by researchers from the Chinese University of Hong Kong (CUHK) is shown in a randomized controlled trial to reduce the risk of bacterial and viral infections, including COVID-19, reduce the risk of adverse events (AEs) after COVID-19 vaccination, restore healthy gut microbiota, and provide other health benefits.

The formula, known as SIM01, was evaluated in the double-blind IMPACT study in 453 individuals with diabetes or aged ≥65 years (mean age, 67.5 years; female, 50.3 percent; mean body weight, 63.7 kg; nonsmokers, 84.7 percent; nondrinkers, 85.4 percent; hypertension, 49.2 percent; diabetes, 47.5 percent; hyperlipidaemia, 47 percent) who had received one dose of COVID-19 vaccine.

Recruited in 2021–2022, the participants were randomized to receive SIM01 (n=224) or a vitamin C placebo (n=229) for 3 months, and evaluated at 1 month, 3 months, 6 months and 12 months after second-dose COVID-19 vaccination.

Results showed lower rates of viral and bacterial infections, including COVID-19, dermatitis, sepsis and wound infections, in the SIM01 vs placebo group. “Rates of infections were 0.5 percent vs 5.6 percent at 1 month, 0 percent vs 0.6 percent at 3 months, 4.8 percent vs 15.5 percent at 6 months, and 5.4 percent vs 14.4 percent at 12 months,” reported Professor Martin Wong of the Jockey Club School of Public Health and Primary Care, CUHK.

At 1 month after receiving the second dose of COVID-19 vaccine, AEs were reported in 2.9 percent vs 12.6 percent of the SIM01 vs placebo group (mRNA-based BNT162b2 recipients, 2.4 percent vs 7.1 percent; inactivated CZ02 recipients, 0.5 percent vs 5.6 percent).

Using next-generation shotgun metagenomics sequencing, the researchers evaluated gut microbiota in stool samples from 258 participants (BNT162b2 recipients, n=186; CZ02 recipients, n=72) at 3 months after their second dose of COVID-19 vaccine.

“Results showed restoration of healthy gut microbiota in the SIM01 group,” reported Professor Lin Zhang of Department of Medicine and Therapeutics, CUHK.

In BNT162b2 recipients, a 12.3 percent relative increase in abundance of 30 good bacteria and a 48.6 percent relative decrease in abundance of harmful bacteria were found in the SIM01 vs placebo group. Among CZ02 recipients, a 22.7 percent relative increase and a 35.8 percent relative decrease were found, respectively, with SIM01 vs placebo.

“Notably, among BNT162b2 recipients, a 56 percent [relative] increase in good bacteria associated with reduced vaccine AEs was found with SIM01 vs placebo,” said Zhang.

“SIM01 recipients also had improved sleep quality [41.4 percent vs 19.3 percent], more positive mood [21.1 percent vs 11.4 percent], and improved skin condition [14.1 percent vs 7.0 percent] vs placebo recipients,” reported Professor Siew Ng, Director of Microbiota I-Centre, CUHK.

In a more recent study in April–August 2022, the researchers evaluated SIM01 in 95 children and adolescents aged 5–17 years (female, 52 percent) who received ≥1 dose of COVID-19 vaccine. Compared with historical controls vaccinated with BNT162b2, rates of AEs after vaccination were lower in those who took SIM01. [Comirnaty Product Monograph, 18 February 2022]

“Injection site pain, induration and swelling, redness, itching, pruritus, and erythema were reported in 71 percent of SIM01 recipients vs 90 percent of controls. Fatigue, weakness or lack of energy, and sleepiness were reported in 30 percent vs 75 percent. Headache was reported in 10 percent vs 72 percent, chills were reported in 3 percent vs 45 percent, and muscle pain was reported in 0 percent vs 40 percent,” said Ng. “Most children and adolescents [96 percent] who took SIM01 reported no chest discomfort after vaccination.”