Study: Seven-strain probiotic supplementation treats asthma via miRNA regulation
Asthma is one of the most common chronic inflammatory diseases and its prevalence has increased in the past decades.
A potential mechanism underlying this high prevalence is the microbial hypothesis which argues that less microbial exposure upregulates the cytokine production of T-helper cells type 2 (Th2), leading to an increase in allergic diseases.
The mechanisms that cause allergic diseases in early life are not yet fully understood but research has begun to unpick the impact of the gut microbiome and its affect on the maturation of the immune system, which potentially leads to allergic Th2-type responses.
Probiotics have been found to help regulate cytokine gene expression and the immune system, enhance mucosal barrier function, and compete with pathogenic bacteria.
Probiotics have also been shown to regulate miRNA expression. MicroRNAs (miRNAs) are an evolutionary class of endogenous non-encoding RNAs that destroy or inhibit mRNA translation and thus maintain body homeostasis.
However, there are limited studies on the role of miRNAs in the regulation of intestinal microbiota as a treatment for disease or the capacity of the host to regulate intestinal microbiota in a miRNA-dependent manner.
The current study, involving 40 asthma patients, was designed to investigate the effects of probiotics on clinical symptoms, changes in cytokines and microRNAs, and pulmonary function in patients with asthma.
This was a randomised, double-blind, placebo-controlled trial initially involving 40 asthmatic patients. Five patients were excluded from the study after randomisation and enrolment (three in the probiotic and two in the placebo groups). Eligible patients were randomly divided into probiotic and placebo groups and treated with 1 capsule per day for 8 weeks.
The study utilised a supplement (Lactocare, Zist-Takhmir, Iran) including seven strains of beneficial bacteria: Lactobacillus casei 3 × 109 CFU/g, Lactobacillus acidophilus 3 × 109 CFU/g, Lactobacillus rhamnosus 7 × 109 CFU/g, Lactobacillus bulgaricus 5 × 108 CFU/g, Bifidobacterium breve 2 × 1010 CFU/g, Bifidobacterium longum 1 × 109 CFU/g, and Streptococcus thermophilus 3 × 108 CFU/g, and 38.5 mg fructo-oligosaccharide.
Blood samples were taken from patients before and 60 days after the intervention. At each visit, patients underwent a physical examination, measurement of blood pressure, heart rate, and pulmonary function, and evaluation of asthma symptoms, asthma exacerbations, and adverse events.
The primary outcomes after treatment were asthma control test (ACT) scores, Forced Expiratory Volume in first second (FEV1), Forced Vital Capacity (FVC) and Forced Expiratory Volume in first second (FEV1)/Forced Vital Capacity (FVC) ratio. The secondary outcomes were changes in AQLQ scores (quality of life questionnaire scores), gene expression of miR-21, miR-155, miR-146a, miR-126, miR-16, and miR-133b in plasma as well as IL-4 and IFN-γ plasma levels during the 2 months’ intervention.
The researchers found that eight-week treatment with probiotic supplementation led to reduced Th2 cells-associated IL-4 and improved Forced Expiratory Volume and Forced Vital Capacity. The authors therefore conclude that probiotics can be used in addition to common asthma treatments.
The results showed that the FEV1 and FVC in the probiotic group at the end of the intervention were significantly higher than at the beginning of the study (p < 0.01 and p < 0.001 respectively).
The probiotic group displayed a significant decrease in the IL-4. IFN-γ production in the plasma was also higher in the probiotic-treated group after treatment but not significantly different compared to baseline. There was no significant change in either of these levels in the placebo group.
Findings showed a significant difference in the expression of miR-146a, miR-16, miR-133b in the intervention group, compared to baseline, as well as a decrease in both miR-146 and miR-16 as inflammation-related miRNAs in comparison with baseline (p < 0.05). Also, the expression of miR-16 in the probiotic group was significantly lower than the placebo group (p < 0.05). In addition, the expression of miR-133b in the probiotic group was increased compared to the beginning of the study (p < 0.05).
Patients in the probiotic group also had significant improvement in ACT (asthma control test) and AQLQ (quality of life questionnaire) scores compared to baseline (p < 0.001 and p < 0.0001 respectively).
The authors conclude: "Since quality of life and pulmonary function parameters of patients were improved, and also inflammatory-associated miRNAs and Th2-related IL-4 were reduced, our findings suggested that probiotics can be used short-term for asthmatic patients but long-term consumption of probiotic supplement requires more clinical trials."
The authors note the study was conducted during the COVID-19 pandemic, making it more difficult to select uninfected patients. Therefore, the enrolled patients were not sufficiently large to achieve definitive conclusions, meaning further studies with large populations are warranted.
The team also note they did not take stool samples to check the differences in bacterial counts and species between the probiotic and placebo groups and they did not assess the count of Th1/Th2/Th17/Treg profile before and after the intervention.
Source: Allergy, Asthma & Clinical Immunology
"Immunomodulatory effects of probiotic supplementation in patients with asthma: a randomized, double-blind, placebo-controlled trial"
Sadrifar, S., Abbasi-Dokht, T., Forouzandeh, S. et al.