Synbiotic supplementation may ease long COVID: RCT

By Stephen Daniells

- Last updated on GMT

© Lais Depieri / Getty Images
© Lais Depieri / Getty Images

Related tags COVID-19 long COVID synbiotics microbiome fatigue

Supplementation with a prebiotic-probiotic combination may help with some long COVID problems such as fatigue, memory, concentration and gastrointestinal upset, says a new large study from Hong Kong.

Data published in The Lancet Infectious Diseases​ indicated that a synbiotic supplement containing three probiotic strains and three prebiotics also significantly alleviated general unwellness compared to placebo.

“This randomized, double-blind, placebo-controlled trial showed that treatment with SIM01 [the synbiotic], which targets gut dysbiosis and potentially modifies the immune response, was effective in alleviating multiple symptoms of PACS [Post-acute COVID-19 syndrome]”, wrote scientists from the Chinese University of Hong Kong.

“We identified favorable changes in the gut microbiome, including increased bacterial diversity and short-chain acid-producing bacteria and decreased resistome in the SIM01 group but not placebo group after 6 months of treatment, as plausible mechanisms to account for the clinical improvement.”


Some people who have been infected with the SARS-CoV-2 virus can experience long-term effects from their infection, known as chronic COVID syndrome or long-COVID. While the symptoms are variable, the most common include fatigue, “brain fog” (difficulty thinking or concentrating), gastrointestinal issues, joint pain and more.

According to the U.S. Centers for Disease Control and Prevention (CDC)​, “living with Long COVID can be hard, especially when there are no immediate answers or solutions.”

This new study included 403 people with PACS (long COVID) according to CDC criteria who were randomly assigned to receive either the synbiotic or placebo for six months. The supplement was formulated to deliver three probiotics—Bifidobacterium  adolescentis, B. bifidum​ and B. longum ​at a total daily dose of 20 billion colony forming units (CFU)—plus a combination of three prebiotics—galacto-oligosaccharides, xylo-oligosaccharides and resistant dextrin. The specific strains are not revealed in the study nor is the prebiotic dose.

Key results

Following the six-month intervention, the researchers report that significantly higher proportions of the synbiotic group had alleviation of fatigue, memory loss, difficulty in concentration, gastrointestinal upset and general unwellness compared to the placebo.

Analysis of gut bacterial diversity revealed that all patients (regardless of antibiotic treatment) showed decreased diversity and lower abundance of different Bifidobacterium strains, “suggesting that SARS-CoV-2 infection might also have an effect on the gut microbiome in these cases”, they said.

“The exact cause for this finding is unknown but could be the effect of SARS-CoV-2 or immune dysfunction in COVID-19,” they added.

A causal link between the gut microbiome and immune dysfunction in COVID-19 is difficult to ascertain in human studies, noted the researchers, but data from animal studies indicates that the virus may change the gut microbiome.

“To date, studies using probiotic intervention to alleviate PACS are sparse, and the optimal dose, duration or type of bacteria requires further interventional trials,” they wrote. “In conclusion, we found that our synbiotic preparation, SIM01, alleviated multiple symptoms of PACS at 6 months in adult patients after acute COVID-19 infection. Our findings support the potential of gut microbiome-targeted therapeutics for PACS in the post-COVID era.”

Source: The Lancet Infectious Diseases
Published online ahead of print, doi: 10.1016/S1473-3099(23)00685-0
“A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial”
Authors: R.I. Lau, et al.

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