Long COVID and Probiotics: What Research Suggests
As researchers investigate potential treatments for long COVID, the gut microbiome has emerged as a promising target. Studies show that people with long COVID often have disrupted gut bacteria, and preliminary research suggests that probiotics might help alleviate some symptoms. Here’s what the evidence shows about using probiotics for long COVID.
This article walks through the connection between gut health and long COVID, what clinical trials have found, and what we know about which probiotic strains might be most relevant.
The Gut Microbiome Connection in Long COVID
Patients with long COVID consistently exhibit reduced microbial diversity and depletion of beneficial bacteria. Specifically, they show lower levels of short-chain fatty acid producing species like Faecalibacterium prausnitzii and Bifidobacterium species.
At the same time, there’s enrichment of proinflammatory bacteria including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These changes may disrupt intestinal barrier integrity and sustain low-grade systemic inflammation.
This persistent dysbiosis appears linked to ongoing symptoms. The question is whether restoring a healthier gut microbiome might improve those symptoms.
The SIM01 Clinical Trial: The Strongest Evidence
The largest randomized controlled trial to date tested a synbiotic formula called SIM01 in 463 long COVID patients in Hong Kong. The study was published in The Lancet Infectious Diseases in 2023.
SIM01 contains three strains of Bifidobacterium bacteria (B. adolescentis, B. bifidum, and B. longum) along with three prebiotic fibers (galacto-oligosaccharides, xylo-oligosaccharides, and resistant dextrin). Patients took it twice daily for six months.
After six months, significantly higher proportions of the probiotic group reported improvement in fatigue, memory loss, difficulty concentrating, gastrointestinal upset, and general unwellness compared to the placebo group.
The specific improvements were notable. The probiotic group showed a 47% increase in fatigue relief, 56% in memory loss improvement, 62% in concentration improvement, 30% in gastrointestinal symptoms, and 31% in general unwellness reduction.
What the Trial Actually Measured
These are symptom improvement rates, not cure rates. People reported feeling better, but many still had some level of symptoms. The improvement was relative to baseline and compared to placebo.
Importantly, the study found no significant difference in quality of life scores or physical activity levels between groups at six months. This suggests that while specific symptoms improved, overall functional capacity didn’t change as dramatically.
How Probiotics Might Work for Long COVID
The synbiotic formula significantly improved gut microbiota functions, potentially promoting release of short-chain fatty acids and inhibiting urea production. Short-chain fatty acids like butyrate have anti-inflammatory properties and support immune function.
Decreased abundance of short-chain fatty acid-producing bacteria in the gut might represent one of the crucial mechanisms contributing to disease severity in COVID-19 through the gut-lung interaction.
The Gut-Brain and Gut-Lung Connections
The fact that memory and concentration problems improved supports the importance of the gut-brain axis. Restoring healthy gut microbiota appears to be a novel approach to improving neurological symptoms.
Gut dysbiosis can influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. These bidirectional communication systems help explain why gut bacteria changes might affect symptoms throughout the body.
The gut microbiome doesn’t just affect digestion. It influences immune function, inflammation throughout the body, and even brain function through these interconnected pathways.
Other Research on Probiotics and Long COVID
A 2025 review in Gut Microbes examined clinical trials using probiotics, prebiotics, and fecal microbiota transplantation for long COVID. These approaches led to improvements in multiple symptoms including fatigue, memory loss, difficulty concentrating, gastrointestinal upset, and disturbances in sleep and mood.
A systematic review of 27 studies found that the majority of probiotic and synbiotic interventions exhibited positive effects, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates during acute COVID.
Studies using probiotics during acute COVID infection showed mortality rates ranging from 0% to 11% in intervention groups compared to 3% to 30% in control groups. While these studies focused on acute infection rather than long COVID, they demonstrate biological plausibility.
Which Bacterial Strains Show Promise
Research highlights specific probiotic species including Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum for their potential role in alleviating long-term COVID symptoms.
The SIM01 formula specifically used Bifidobacterium species because these strains had the greatest positive correlations with short-chain fatty acid-producing bacterial species in the researchers’ metagenomic datasets.
Prebiotics and Synbiotics: Why Combination Matters
The concurrent use of prebiotics and probiotics is considered crucial. Prebiotics feed the beneficial bacteria, helping them establish and thrive in the gut.
The rationale for synbiotics—combinations of probiotics and prebiotics—is that they address the multifactorial nature of long COVID more comprehensively than either component alone.
Study Limitations and Unanswered Questions
The SIM01 trial had limitations including single-center design and a formulation based on gut flora of healthy Chinese populations. Whether findings apply to ethnically and geographically diverse populations needs investigation.
The proposed mechanism—symptom improvement through reduced systemic inflammation via increased gut microbial diversity—is intriguing but remains partially speculative. No differences were observed in plasma cytokine profiles between groups at six months.
We don’t know how SIM01 compares to other probiotic formulations containing Lactobacillus species or different Bifidobacterium strain combinations. Comparative research is needed.
Some researchers note the need for more comprehensive scientific research to definitively confirm effectiveness before making treatment decisions based on current evidence alone.
What About Regular Probiotic Supplements?
The SIM01 formula used in the trial is not widely available. It was specifically developed through machine learning analysis of microbiome data and contains particular strains at specific ratios.
Over-the-counter probiotic supplements typically contain different strains, different ratios, and often lower colony-forming units than research formulations. Whether they would produce similar benefits is unknown.
Several studies show that probiotics consisting of beneficial bacteria such as Lactobacillus and Bifidobacterium species might enhance gut health, modulate inflammation, and improve immune function. But specific formulations and dosing matter.
Safety Considerations
Probiotics are generally considered safe for most people. However, people with severely weakened immune systems or serious underlying health conditions should consult healthcare providers before starting probiotics.
In rare cases, probiotics can cause infections in immunocompromised individuals. People with central venous catheters or other indwelling medical devices should be especially cautious.
Digestive side effects like gas, bloating, or changes in bowel movements are possible, especially when first starting probiotics. These usually resolve within a few days.
Dosing and Duration
The SIM01 trial used 20 billion colony-forming units daily (10 billion twice daily) for six months. This is a relatively high dose compared to many over-the-counter probiotics.
The six-month duration was significant. Shorter trials might not show the same benefits, as gut microbiome changes take time to establish.
Whether benefits persist after stopping probiotics is unknown. The gut microbiome can shift again once supplementation ends, though dietary and lifestyle factors also influence it.
The Role of Diet and Lifestyle
Probiotics work alongside diet. Nutritional status and diet play crucial roles, predominantly owing to the bidirectional interaction between the lungs and the gut microbiota.
Eating a diet rich in fiber and fermented foods supports beneficial gut bacteria. Avoiding excessive processed foods, sugar, and artificial sweeteners may help maintain a healthier microbiome.
Stress, sleep, physical activity, and medications (especially antibiotics) all affect gut bacteria. Probiotics are one tool, but they work best as part of an overall approach to health.
What This Means for People with Long COVID
The evidence suggests probiotics might help some long COVID symptoms, particularly fatigue, cognitive problems, and gastrointestinal issues. The effect isn’t dramatic for everyone, but it’s measurable in research.
This is preliminary but promising research. One well-designed trial showing benefit is encouraging, but it’s not definitive proof that all probiotics help all long COVID patients.
Probiotics represent a promising solution to mitigate long COVID symptoms by restoring gut microbiota balance and modulating immune response. But we need more research on which formulations work best and for whom.
If you’re considering probiotics for long COVID, discuss it with your healthcare provider. They can help you choose appropriate strains and doses based on your specific symptoms and health status.
The Bottom Line
Research shows a clear connection between gut microbiome disruption and long COVID symptoms. A large randomized trial found that a specific synbiotic formula improved fatigue, memory, concentration, and gastrointestinal symptoms in long COVID patients.
The evidence is encouraging but not conclusive. Most research has focused on one particular formulation. Whether over-the-counter probiotics produce similar benefits is uncertain.
Probiotics appear safe for most people and might be worth trying as part of a comprehensive approach to managing long COVID. Set realistic expectations—improvements may be moderate rather than transformative.
This is an active area of research. What we know in 2026 will likely be different from what we know in 2028 or 2030. As more trials are completed, we’ll have better guidance on which probiotics to use, at what doses, and for which symptoms.
