Probiotics combined with prebiotics alleviated seasonal allergic rhinitis by altering the composition and metabolic function of intestinal microbiota: a prospective, randomized, double-blind, placebo-controlled clinical trial

Abstract

Background: Numerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms.

Methods: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry.

Results: 106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P <0.001). After the administration of probiotics and prebiotics, the composition and metabolic function of the intestinal microbiota were significantly altered and positively related to the beneficial effect on seasonal AR patients.

Conclusion: Probiotics combined with prebiotics administered for 90 days significantly attenuated the symptoms of seasonal AR patients, which may related to fluctuations in the composition and metabolic function of the intestinal microbiota and further ameliorating host immunity.

Keywords: allergic rhinitis; immunity; intestinal microbiota; probiotics and prebiotics; shortchain fatty acids.

Figure 1

CONSORT flow diagram of participant.

Figure 2

Differences in intestinal microbiota at different time points between the test group and placebo group. (A) PCoA between the test group and placebo group. (B) Differences in alpha diversity between groups. (C) PCoA and Permanova analysis between groups. (D) Stack distribution of phylum in different groups. (E) Analysis of different intestinal microbiota between groups at the genus level on days 31, 61, and 91. (F) Mean changes of Bifidobacterium, Bifidobacterium animalis, Lactobacillus acidophilus, Lactobacillus, and Bifidobacterium longum from baseline; data are expressed as mean ± SE. ^# P < 0.05, ^## P < 0.01, ^### P < 0.001 for the difference from baseline within groups. ^* P < 0.05, ^** P < 0.01, ^*** P < 0.001 for the difference between groups. PCoA, principal coordinate analysis; X, placebo group; Y, probiotics and prebiotics group.

Figure 3

The function of intestinal microbiota. (A) Principal component analysis of function prediction. (B) Differences in function prediction of microbiota between the test group and placebo group on days 31, 61, and 91. (C) Mean change in total acids and percentages of acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate from baseline; data are expressed as mean ± SE. Covariance analysis was used to compare differences from baseline levels between the two groups. ^# P < 0.05, ^## P < 0.01, ^### P < 0.001 for the difference from baseline within groups. ^* P < 0.05, ^** P < 0.01, ^*** P < 0.001 for the difference between groups. X, placebo group; Y, probiotics and prebiotics group.

Figure 4

Heat map of correlation analysis. (A) Correlations between intestinal microbiota and clinical indicators. (B) Correlations between microbiota function and clinical indicators. ^* P < 0.05, ^** P < 0.01, ^*** P < 0.001. r, related coefficient; TNSS, total nasal symptom score. Red asterisks represent positive correlations, and black asterisks represent negative correlations.