Read Time: 4 Minutes

Research continues to illustrate the extensive and important bidirectional relationship between gut and immune health. Specific to respiratory infections, the gut’s microbial composition may determine either appropriate or dysfunctional immune responses,^1-3 and modulating the gut microbiota through probiotic use has been shown to help prevent infection and improve outcomes.⁴ A new systematic review in the December 2021 issue of the European Journal of Nutrition explores the protections offered by probiotic strains on viral respiratory tract infections.⁵

Modulating the Microbiota: A Systematic Review of Probiotics and Viral RTIs

Investigators conducted a systematic review of studies published through April 2020 that reported the effect of gut microbiota modulation on viral respiratory tract infections (RTIs) in both clinical studies and animal models.⁵ Specifically, the aims of the systematic review were twofold:⁵

• To determine the efficacy of gut microbiota modulation using probiotics on viral RTI outcomes in clinical studies.
• To explore the role of probiotics in the protection against viral RTIs in animal models.

While other reviews have tracked the relationship between probiotic use and RTIs, the researchers in this study limited the definition of RTIs to only those caused by a virus and included only those RTI studies where viral etiologies were confirmed by virology tests.

Probiotic Strains & Prebiotics: Clinical Trial Results

The systematic review included 58 studies (nine human trials (n=1,240) and 49 animal studies). The human studies were conducted between 2013 and 2019, with five focused on adults (n=675), two on elderly subjects (n=303), one on children (n=194), and one on preterm infants (n=68). In the clinical trials, three probiotic strains were noted:⁵

• Lactobacillus was the most commonly used probiotic; dose range of 1 x 10⁸ CFU/day to 1 x 10¹¹ CFU/day; in the form of a yogurt beverage, capsule, milk formula, dissolved powder, or a chewing tablet; with treatment durations between six and 28 weeks.
• Bifidobacterium was the second most common; dose range of 2 x 10⁹ CFU/day to 4 x 10⁹ CFU/day; in the form of dissolved powder or a chewing tablet; with treatment durations between five and 21 weeks.
• Lactococcus was used in one trial; dose of 1 x 10¹¹ CFU/day; in the form of a yogurt beverage; with a treatment duration of 10 weeks.
• Prebiotics in the form of galacto-oligosaccharide and polydextrose mixtures were also evaluated in one trial; dose of 1 × 600 mg/day for 1 to 30 days and 2 × 600 mg/day for 31 to 60 days.

Investigators noted that heterogeneity hindered direct comparison of individual studies; however, overall results from the systematic review included the following:⁵

• Viral Infection Rate: Of important clinical relevance, among the eight trials that reported virus infection rate, six showed decreased rates of RTIs in the probiotic group compared to placebo.
• Viral Load: Among the three studies that evaluated the impact of probiotics on viral load, one found that compared to placebo, pretreatment with four weeks of Bifidobacterium resulted in a smaller number of participants with virus shedding in nasal secretion. Another study reported a tendency toward lower viral load in those participants treated with three weeks of Lactobacillus.
• Clinical Symptoms: Among the four studies that investigated the effect of probiotics on clinical symptoms caused by viral RTIs, only one reported a trend toward improved symptoms. Overall, the studies did not find that the probiotic treatments significantly improved the severity of clinical symptoms associated with viral RTIs.
• Prebiotics: Only one included study evaluated the effects of prebiotics and found that among preterm infants, the prebiotic treatment significantly reduced the risk of viral RTIs compared with placebo during a 12-month follow-up. Investigators noted that there were no significant differences noted between prebiotic treatment and placebo for viral load or severity of clinical symptoms.

Specific to the clinical trials in this systematic review, investigators concluded that modulation of the gut microbiota through probiotic use may help to prevent viral RTIs.⁵

Mechanisms in Animal Models

As clinical research into the gut microbiota and immunity continues to develop, animal models present opportunities to better understand the biological mechanisms that may be at play. Of the 49 animal studies included in this systematic review, 36 investigated the effects of probiotic ingestion on outcomes of viral RTIs. Most of the studies used Lactobacillus, followed by Bifidobacterium, Enterococcus, or Lactococcus. The probiotics administered before viral challenges demonstrated beneficial effects against viral infection by improving infection-induced survival, mitigating symptoms, and decreasing viral load.⁵

In the animal models, the protective response of probiotics and commensal gut microbiota strengthened host adaptive and innate immunity through several noted mechanisms, including the involvement of specific immune cells. Upon probiotic administration, several studies reported increased natural killer cell activities and increased recruitment of dendritic cells.⁵ Related to the modulation of antiviral immunity, probiotic administration also increased production of either interferon-alpha or beta, decreased interleukin-6, upregulated interleukin-10, and increased production of viral-specific IgA and IgG.⁵

A Dietary Approach

In functional medicine, gut health is an important pillar of therapeutic approaches for the treatment and prevention of chronic disease. Addressing dysbiosis and modulating the gut microbial landscape through nutritional support may include prebiotic and fermented foods in addition to appropriate probiotic supplementation. A recent meta-analysis of 22 randomized controlled trials (n=10,190) included trials that investigated whether the consumption of fermented dairy products prevented RTIs in different age groups.⁶ The results suggested that compared with placebo, intake of the fermented dairy products had a significant protective effect against RTIs overall (19% protection), with the following rates in children (18% protection), adults (19% protection), and elderly populations (22% protection).⁶

As the clinical research uncovers additional details on fermented foods, probiotic strains, dosage amounts, and treatment durations, we will better understand the benefits and clinical applications of potential probiotic treatments, not only for disease management but also for their role in promoting immune resilience and overall wellness.

Related Articles

Innate Immunity: Diet and Lifestyle Support

Prebiotic Foods for Postbiotic Abundance

Gastrointestinal Involvement in COVID-19: Research and Interventions

References

1. Hanada S, Pirzadeh M, Carver KY, Deng JC. Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. Front Immunol. 2018;9:2640. doi:10.3389/fimmu.2018.02640.
2. Chunxi L, Haiyue L, Yanxia L, Jianbing P, Jin S. The gut microbiota and respiratory diseases: new evidence. J Immunol Res. 2020;2020:2340670. doi:10.1155/2020/2340670.
3. Yeoh YK, Zuo T, Lui GC-Y, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698-706. doi:10.1136/gutjnl-2020-323020.
4. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;(2):CD6895. doi:10.1002/14651858.CD006895.pub3.
5. Shi HY, Zhu X, Li WL, et al. Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies. Eur J Nutr. 2021;60(8):4151-4174. doi:10.1007/s00394-021-02519-x.
6. Rashidi K, Razi B, Darand M, Dehghani A, Janmohammadi P, Alizadeh S. Effect of probiotic fermented dairy products on incidence of respiratory tract infections: a systematic review and meta-analysis of randomized clinical trials. Nutr J. 2020;20(1):61. doi:10.1186/s12937-021-00718-0.