Do multi-strain probiotics improve long covid symptoms?

By Dr. Liji Thomas, MDReviewed by Lauren HardakerMar 27 2026

Can probiotics help rebalance the disrupted gut in long COVID? New research reveals subtle microbiome shifts and hints at metabolic benefits, but stops short of confirming meaningful clinical improvement. 

Study: Multi-Strain Probiotic Intervention Modestly Modulates Microbial Composition and Inflammatory Profile in Individuals with Long COVID. Image credit: Anna Gawlik/Shutterstock.com

A new study in Microorganisms suggests that multi-strain probiotics can produce modest, targeted shifts in the gut microbiome of people with long COVID, but any downstream benefits, such as reduced inflammation or improved liver-related biomarkers, remain limited and not statistically significant. 

Gut dysbiosis may drive persistent long COVID symptoms

Probiotics are increasingly being explored as a potential way to support recovery in people with long COVID. Widely used for their effects on the gut microbiome, they are also known to influence immune and metabolic processes. However, their effectiveness in addressing long COVID remains uncertain.

Modulating the gut microbiome has been proposed as a strategy for treating infections, inflammatory conditions, and metabolic disease, reflecting its central role in maintaining physiological balance. The microbiome helps regulate immune responses, metabolic pathways, the integrity of the gut epithelial barrier, and systemic inflammation.

When this balance is disrupted, a state known as dysbiosis may contribute to disease. Probiotics, which are live beneficial microorganisms, are thought to help restore this balance by reshaping the microbial community.

Probiotics may support the production of beneficial metabolites, including short-chain fatty acids (SCFAs), directly or indirectly via commensal microbes, that promote the growth of other health-associated microbes. SCFAs suppress the growth of potential pathogens and regulate inflammatory responses.

Inflammation was prominent during the recent pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which often led to coronavirus disease 2019 (COVID-19). Existing literature suggests that SARS-CoV-2 triggers persistent inflammation and promotes sustained gut dysbiosis.

Up to 50 % of COVID-19 patients develop prolonged symptoms relating to multiple organs, together called long COVID. The authors explain this as possibly resulting from a bidirectional chain of interactions between secondary viral effects and gut dysbiosis.

There are limited effective treatments for long COVID, prompting active interest in the potential benefits of probiotics. Previous studies have focused primarily on the gut-protective effects of Lactobacillus and Bifidobacterium supplementation.

On the other hand, Saccharomyces boulardii is a yeast known for its anti-inflammatory and gut-protective effects, but its use in long COVID has been little explored. In view of this, the authors propose a broader impact on physiological function with multi-strain probiotics in long COVID compared to single-strain probiotics.

Non-randomized trial evaluates multi-strain probiotics over 12 weeks

The investigators conducted a double-blinded, prospective, non-randomized interventional study with self-reported compliance monitoring. One arm included 23 participants with long COVID, and 26 fully convalescent patients. Long COVID patients had a history of symptoms for 3-27 months after the primary infection, with a median of 14 months.

Of these, 13 and 21 individuals received the intervention for 12 weeks, while 10 and 5 individuals served as controls who did not receive it. In addition, 25 healthy controls with no history of symptomatic COVID-19 served as reference controls and did not receive the supplement. Overall, there were 34 supplemented and 40 non-supplemented participants.

The probiotic formulation contained Saccharomyces boulardii, Lacticaseibacillus rhamnosus GG, and two Lactiplantibacillus plantarum strains. The gut microbiome was assessed by fecal analysis using 16S rRNA gene amplicon sequencing (V3–V4 region). The results were compared with those from a previous cross-sectional analysis of the same cohort. Biochemical changes over the study period were also studied.

Probiotics induce selective changes in the microbiome

The probiotic group showed selective changes in microbial community composition without alteration in overall microbial diversity. When the two subgroups with a history of COVID-19 were compared, long COVID patients showed more marked changes in certain genera than convalescent patients did.

Overall, five genera changed in abundance following the intervention. Bacterial taxa like Adlercreutzia, Ruminococcaceae, and Eubacterium showed an increase, while Coprococcus showed a similar tendency. These genera play a part in microbial metabolism and immune regulation. Earlier studies have reported depletion of these taxa in acute COVID-19 and long COVID, suggesting that probiotic supplementation leads to partial restoration.

Marvinbryantia showed the greatest increase in relative abundance, while the potentially pathogenic Prevotella_9 showed a decrease in abundance, with statistical significance depending on the analytical approach. Interestingly, Lactobacillus abundance remained unchanged, suggesting beneficial effects independent of colonization.

Potential partial restoration of microbial activity

Functional prediction analysis suggested that probiotics in long COVID could increase bacterial energy metabolism and reduce oxidative stress, as inferred from pathway enrichment, reflecting predicted changes consistent with improved microbial respiration. Simultaneously, there was a statistically insignificant trend toward reduced host inflammation and lower hepatic enzyme levels.

Spearman analysis revealed 217 correlations between microbial shifts and host biochemical responses in long COVID patients, though these represent associations and do not imply causation. This included associations between increased abundance of genera like Negativibacillus and lower liver enzyme levels. Changes in other genera, such as Tannerellaceae, were negatively associated with inflammatory markers and liver enzymes.

Long COVID patients show modest microbial benefit from probiotics

The authors cite their earlier work to show that gut dysbiosis is associated with long COVID but not with fully convalescent patients. In this study, probiotics altered specific microbial taxa but did not change overall diversity. The changes were small but affected relevant taxa and pathways.

Long COVID patients showed a greater number of differentially affected taxa, perhaps reflecting greater responsiveness to microbial manipulation, particularly in the context of persistent baseline dysbiosis. This might be due to the prolonged dysbiosis and metabolic derangements in long COVID.

In contrast, convalescent patients showed less change, indicating their greater microbiome stability after recovery. This is supported by existing research.

Several of the enriched genera are associated with anti-inflammatory processes, which could aid recovery from long COVID-19. Conversely, Prevotella_9 is enriched in inflammation and dysbiosis, including in acute COVID-19 and long COVID. This taxon was decreased post-intervention.

Biochemical tests showed consistent, though modest, trends toward normalcy with supplementation. Though not statistically significant, they corroborate earlier reports showing associations between inflammatory and metabolic shifts and gut dysbiosis in long COVID.

Although the study's findings are biologically plausible, they are limited by a small sample size, non-randomized allocation, and the use of functional prediction analysis rather than actual metagenomic measurements. Methodological biases in the technology used may also affect the results.

Despite this, different streams of analysis consistently suggested the potential value of multi-probiotic supplementation in long COVID, though the results remain statistically insignificant.

Overall, probiotic intervention demonstrated microbiota-status-dependent potential in long COVID recovery.

The probiotic formulation was supported in part by an industry source, though the funder reportedly had no role in study design, analysis, or interpretation.

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