Research Advances in the Treatment of Allergic Rhinitis by Probiotics

Figures & data

Figure 1 Pattern of pathogenesis of allergic rhinitis.

Abbreviations: DC, dendritic cell; B, B cell; IL, interleukin; ILC, type 2 innate lymphocytes; IgE, immunoglobulin E; TH2, type 2 helper T lymphocyte; TfH, follicular helper T lymphocyte.

Table 1 Treatment Options for Allergic Rhinitis^5,19

Mode of Administration	Types of Drugs	Clinical Treatment	Degree of Recommendation
Oral	Oral corticosteroid	Second-line medication	Use as appropriate
	Oral H1-antihistamine	First-line medication	Recommended use
	Leukotriene receptor antagonist	First-line medication	Recommended use
	Mast cell membrane stabilizer	Second-line medication	Use as appropriate
Intranasal use	Intranasal corticosteroid	First-line medication	Recommended use
	Nasal decongestant	Second-line medication	Use as appropriate
	Nasal H1-antihistamine	First-line medication	Recommended use
	Intranasal corticosteroid plus H1-antihistamine	Second-line medication	Use as appropriate
	Intranasal anti-cholinergic agent	Second-line medication	Use as appropriate

Table 2 CIassification of Probiotics and Common Representative Strains

CIassification	Representative Strains	Author
Streptococcus	Viridans Streptococcus, Streptococcus thermophilus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus lactis, Streptococcus faecalis, Streptococcus platus, etc.	Jin et al^Citation43
Lactobacillus	Lactobacillus lactis, Lactobacillus paracasei, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus plantarum, etc.	Xie et al^Citation44
Bifidobacteria	Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium adolescentis, Bifidobacterium thermophilus, etc.	Liu et al^Citation45
Bacillus	Bacillus licheniformis, Bacillus megaterium, Bacillus natto, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus anthracis, Bacillus sphaericus, etc.	Cui et al^Citation46
Other classes	Escherichia coli, Photosynthetic bacteria, Propionibacterium, Football bacteria, Escherichia coli, yeast, etc.	Wang et al^Citation47 Fei et al^Citation48

Table 3 Recent Investigations into the Use of Probiotics for Allergic Rhinitis

Author and Date	Type of Study	Probiotic Type	Dosage and Time of Exposure	Main Findings	Possible Mechanisms	Quality of Life and Symptoms, and so on
Xu et al 2016^Citation59	Randomized, double-blind, placebo-controlled crossover study with 15 adults	Clostridium butyricum (Cb)	Unclear dose for 7 months	IgE, B cells↓ Th2 cells↓ Treg, IL10↑	Inhibition of Th2 immune response	Add-on probiotic therapy enhanced SCIT in patients with AR
Jerzynska et al 2016^Citation61	Prospective and double-blind, randomized, placebo-controlled with 100 children	L. rhamnosus GG	1000 IU daily for 5 months	IL1, IL6↓ IL10, IL12, TGFβ↑ Th1 cells↑ CD4+CD25+Foxp3+↑	Enhance immune response	Add-on probiotic therapy enhanced SLIT in children with AR
Del et al 2017^Citation52	Randomized, double-blind, placebo-controlled study with 40 children	B. longum BB536, B. infantis M-63, B. breve M-16V	B. longum BB536 (3x10^9 CFU), B. infantis M-63 (1x10^9 CFU), and B. breve M-16 V (1x10^9 CFU) daily for 8 weeks	##	##	Improved AR symptoms and QoL
Berings et al 2017^Citation55	Randomized, double-blind, placebo-controlled crossover study with 20 adults	B. subtilis, B. amyloliquefaciens, B. pumilus strains	Bedding for house Purotex^® covers 8 weeks	##	##	Improved AR symptoms and QoL
Qiao et al 2017^Citation57	Double-blind, placebo-controlled with 40 adults	Clostridium butyricum duplex viable	3 capsules/time Twice a day for 6 weeks	IL10, TGFβ↑	Inhibition of Th2 immune response	Improved AR symptoms and VAS, RQLQ
Juan et al 2017^Citation66	Randomized, double-blind, placebo-controlled study with 40 BALB/c mice	Clostridium butyricum CGMCC0313-1	1×10^8 CFU daily for 2 weeks	IL4, IL5, IL13, IL17↓ IgE/G1↓ IL10↑ CD4+CD25+Foxp3+↑	Th1/Th2 Cytokine balance	Alleviates inflammation
Harata et al 2017^Citation121	Double-blind, randomized, placebo-controlled study with 25 pollinosis patients	Lactobacillus rhamnosus GG Lactobacillus gasseri TMC0356	110g fermented milk daily for 10 weeks	Restore intestinal microbiota balance	Regulating blood lipids	Alleviates inflammation
Choi et al 2018^Citation65	Randomized, double-blind, placebo-controlled study with 35 BALB/c mice	Lactobacillus plantarum CJLP133 and CJLP243	1×10^10 CFU daily for 17 days	IL4, IL5, IL13↓ IgE, IgG1↓ IgG2a, IFNγ↑ Th1 cells↑	Th1/Th2 Cytokine balance	Reduce inflammation and symptoms
Ren et al 2018^Citation72	Randomized, double-blind, placebo-controlled study with # #BALB/c mice	Bifidobacterium breve	Unclear dose for 4 weeks	IL4, IL10↓ IgE↓ CD4+CD25+Tregs↑	Inhibition of Th2 immune response	Improved AR symptoms
Ahmed et al 2019^Citation50	Randomized controlled study with 212 children	L. paracasei LP33	2x10^9 CFU daily for 6 weeks	IgE↓	Promote Th1 immunity and inhibit Th2 response	As effective as cetirizine for perennial AR
Jalali et al 2019^Citation58	Randomized, double-blind, placebo-controlled crossover study with 152 adults	L. acidophilus, L. casei, L. delbrueckii subsp. L. bulgaricus, and L. rhamnosus	11.5×10^10 CFU daily for 8 weeks	##	##	Add-on probiotic therapy was more effective than budesonide
Meng et al 2019^Citation62	Randomized, placebo-controlled study with 60 patients	Broncho-vaxom (BV)	7mg daily for 10 days, resting 20 days, 3 courses	IL4, IL13↓ eosinophils↓ IFNγ↑	Th1/Th2 Cytokine balance	Improved TNSS and INSS score
Makino et al 2019^Citation68	Randomized, double-blind, placebo-controlled study with ## Ovalbumin (OVA)-specific TCR-transgenic DO11.10 mice	L. helveticus SBT2171	Unclear dose for 6 weeks	IL4, IL13↓ Leukocyte infiltration↓ IL10, IFNγ↑ Th1 cells↑	Th1/Th2 Cytokine balance	Alleviates allergic symptoms
Schaefer et al 2019^Citation122	Randomized, double-blind, placebo-controlled crossover study with 120 patients	Enterococcus faecalis	30 drops each time, 3 times daily for 8 weeks	Restore intestinal microbiota balance	Regulate immune response	Improved AR symptoms
Kim et al 2019^Citation123	Randomized, double-blind, placebo-controlled crossover study with 48 BALB/c mice	Bifidobacterium longum IM55 and Lactobacillus plantarum IM76	2×10^9 CFU daily for 30 days	IL4, IL5↓ Th2 cells, Mast cells ↓ eosinophils, basophils↓ Bacteroides↓ Proteobacteria↑ Actinomycetes↑	Restoring Th2/Treg imbalance and gut microbiota disturbance	Improved AR symptoms
Yamashita et al 2020^Citation51	Randomized, double-blind, placebo-controlled study with 200 adults	L. helveticus SBT2171	10g daily for 12 weeks	IgE↓ eosinophils↓	Th1/Th2 Cytokine balance or Inhibition of Th2 immune response	Improved AR symptoms
Kang et al 2020^Citation53	Multi-center, double-blind, randomized, placebo-controlled with 97 adults	B. longum IM55, L. plantarum IM76	1×10^10 CFU daily for 4 weeks	IL4, IL5, IL13↓ PDG2↓ Cysteine LTs↓ IgE↓ Mast cells↓ B cells↓ eosinophils↓ Th2 cells↓ Treg↑ IL10↑	Th1/Th2 Cytokine balance	Improved TNSS and RCAT score
Anania et al 2021^Citation54	Prospective and double-blind, randomized, placebo-controlled with 250 children	Lactis BB12, Enterococcus faecium L3	4×10^10 CFU daily for 3 months	##	##	Improved NSS score
Bae et al 2021^Citation67	Randomized, double-blind, placebo-controlled crossover study with # #BALB/c mice	Fermented by probiotic bacteria (FRG)	Unclear dose for more than 2 weeks	IL4, eosinophils↓ basophils, IgE↓	Inhibition of Th2 immune response	Alleviates inflammation
Hu et al 2021^Citation124	Randomized, double-blind, placebo-controlled crossover study with 130 children	Lactobacillus reuteri GL-104, Lactobacillus paracasei GL-156, Lactobacillus rhamnosus MP-108	500mg each time, 3 times daily for 12 weeks	Restore intestinal microbiota balance	Restore intestinal barrier function	Alleviates inflammation
Yang et al 2022^Citation71	Randomized, double-blind, placebo-controlled crossover study with # #BALB/c mice	Lactiplantibacillus plantarum NR16	Unclear time and dose	IL12, IFNγ↑	Induce Th1 immune response and balance Th2/Th1 ratio	Improved AR symptoms

Abbreviations: AR, allergic rhinitis; QoL, quality of life; RCAT, rhinitis control assessment test; SCIT, subcutaneous immunotherapy; SLIT, sublingual immunotherapy; NSS, nasal symptom score; INSS, individual nasal symptom score; TNSS, total nasal symptom score; VAS, visual analogue score; RQLQ, rhinoconjunctivitis quality of life scale; ##, not mentioned or not applicable.

Figure 2 Brief mechanism of probiotic treatment of allergic rhinitis. Probiotics protect against allergic rhinitis by reducing serum pro-inflammatory factors, increasing the number of immune cells, regulating Th1 and Th2 balance, increasing Treg numbers, and inhibiting Th17. In addition, probiotics can directly stimulate the formation of TDCs or activate the TLR pathway to indirectly stimulate DC, thereby inducing the formation of Tregs. Probiotics can improve AR by increasing the level of beneficial bacteria to regulate the stability of the gut microbiota, restoring the intestinal mucosal barrier.

Abbreviations: TDC, tolerogenic dendritic cell; IL, interleukin; ILC2s, type 2 innate lymphocytes; IgE, immunoglobulin E; IgG2a, immunoglobulin G2a; IgG1, immunoglobulin G1; Th1, type 1 helper T lymphocyte; Th2, type 2 helper T lymphocyte; Th17, type 17 helper T lymphocyte; TGF-β, transforming growth factor-β; IFN-γ, interferon-γ; TLR4/NF-κB, toll like receptor-4/nuclear factor-κB; Foxp3, forkhead box protein p3; Treg, T regulatory cells.

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