L-92 Clinical Evidence

International Archives of Allergy and Immunology
Torii, S, et al. Effects of oral administration of Lactobacillus acidophilus L-92 on
the symptoms and serum markers of atopic dermatitis in children.
2011;154(3):236–45


Topic
What are the observed effects of an orally administered special strain of Lactobacillus acidophilus
over several weeks’ duration on traditional medical therapy of patients with atopic dermatitis (AD)? 

Background
Lactic acid bacteria probiotics have potential use in the treatment of immune-mediated diseases that involve T-helper type 2 (Th2) cytokines such as allergies, since lactic acid bacteria may be able to modulate the T-helper type 1 (Th1)-to-Th2 balance to improve allergy symptoms. Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 0.3%–20% of children worldwide with symptoms of itchy eczema. L-92 might help when given orally and is thought to improve this condition by lowering the level of allergenspecific immunoglobulin E in the blood by stimulating IL-12 production from dendritic cells to induce the generation of Th1 cells from naïve T cells, which could suppress Th2 responses through the activation of Th1 cells. It also might work through CD4+ T cell responses by reducing CD4+ T cell hyper-responsiveness, especially of Th2 cells. 

Study Type
Human clinical intervention trial

Study Design
An Atopic Dermatitis Area and Severity Index was used to evaluate the symptom severity using a symptom score that took into account the effect of medical therapy by adding a symptom score to a medication score. The medication score calculated the sum of each product of the amount of steroid ointment used for therapy and its designated strength graded on a 4-point scale. Both a preliminary causal study and a double-blind, placebo-controlled study were performed to evaluate the effects of L-92 on the symptoms of AD in children. 

Subjects
50 child patients

Dosage
30 billion colony-forming units of Lactobacillus acidophilus, L-92 strain, taken orally

Results
L-92 significantly reduced symptoms of atopic dermatitis in the subjects. L-92 also influenced the serum concentrations of thymus and activationregulated chemokine in a time-dependent manner. 

Conclusion
The results of the double-blind, placebo-controlled study demonstrated a complementary effect of oral L-92 with standard medical therapy using topical application of a steroid ointment in child patients with AD. It is thought that this effect is mediated to some degree by changes in the Th1-Th2 cytokine balance.

Bioscience Biotechnology Biochemistry
Ishida, Y, et al. Effect of milk fermented with Lactobacillus acidophilus strain
L-92 on symptoms of Japanese cedar pollen allergy: a randomized placebo-controlled trial.
2005 Sep;69(9):1652–60


Topic
How does a daily oral intake of 20 billion L-92 colony forming units (CFUs) in a heat-treated milk medium improve the symptoms of Japanese cedar pollinosis allergies?

Background
Environmental and dietary exposure to microbes may decrease the tendency to allergies. Less exposure to microbes due to sanitary practices may predispose people to more allergic reactions. Th2 cytokines are dominant in allergic disorders, but healthy microflora residence in the gut leads to Th1 cytokine rebalancing by this simulated “infection.” Cedar pollinosis is a widespread seasonal allergy in Japan, and a study examined the effects of Lactobacillus acidophilus strain L-92 on the symptoms of this health problem. The study was carried out during the 2002 and 2003 seasons of Japanese cedar pollination. A similar study was carried out during the 2003 season for 10 weeks with a daily dose of 2 x 1010 CFUs. A significant improvement of the eye symptom-medication score was observed in 2002 and in the distress-of-life score in 2003.

Study Type
Human clinical intervention trial

Study Design
Twenty-three in-house volunteers, 26 to 48 years old, including research and officer staff of Calpis Co., drank 100 mL of heat-treated milk fermented with L-92 containing 50 billion CFUs twice a day for 6 consecutive weeks. The single-blind study was placebo controlled.

Subjects
23 volunteers

Dosage
20 billion heat-treated L-92 CFUs

Results
The data found that a daily oral intake of 20 billion heattreated L-92 CFUs improved the symptoms of Japanese cedar pollinosis, which allowed study subjects to reduce their doses of allergy medications. Th1 cytokines in blood increased while other blood test values were not significantly affected in these trials.

Conclusion
Use of L-92 heat-treated cells fermented with Lactobacillus acidophilus reduced eye and nasal symptoms of a pollen allergy and reduced the need for medication.

Journal of Dairy Science
Ishida, Y, et al. Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis:
a double-blind, placebo-controlled study. 2005 Feb;88(2):527–33


Topic
What are the clinical effects of Lactobacillus acidophilus strain L-92 in a liquid milk base on perennial allergic rhinitis using a symptom severity score to evaluate improvements?

Background
Studies in animals have shown that lactic acid bacteria help alleviate allergic diseases. One proposed explanation for the increased occurrence of allergies is the “hygiene hypothesis.” This idea maintains that less exposure to immune-stimulating pathogens in early childhood causes increased prevalence of allergic diseases, leading to fewer fully developed T-helper type 1 (Th1) cells and causing an intensified immune response toward T-helper type 2 (Th2) cells that promotes humoral immunity, immunoglobulin E (IgE) production, and eosinophilia — all of which predispose one to increased allergic responsiveness. Since Lactobacilli are believed to induce Th1 reaction and improve allergic diseases, and orally administered heattreated Lactobacillus casei (strain Shirota) inhibits IgE production, this may be evidence that allergic disorders can be decreased by ingestion of these bacteria.

Study Type
Human clinical intervention trial

Study Design
In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis randomly received for 8 weeks either 100 mL of heat-treated fermented milk containing L-92 (25 test subjects) or an acidified milk not containing any lactic acid bacteria (24 in the placebo group). The severity of symptoms was evaluated based on changes in the scores of clinical symptoms.

Subjects
49 patients with perennial allergic rhinitis, with 25 test subjects in the L-92 group and 24 in the placebo group

Dosage
30 billion CFUs in 100 mL of heat-treated milk

Results
The L-92 group had a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group showed a trend to improvement compared with those in the placebo group. Decreases in the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 weeks after the start of the study. However, there were no significant differences in serum anti-dust-mite immunoglobulin E levels or in Th1-Th2 ratio between the 2 groups.

Conclusion
Oral administration of L-92 alleviates perennial allergic rhinitis, including nasal symptoms.
Statistically significant changes were not found in blood immune parameters.

International Archives Allergy Immunology
Inoue Y, et. al. Effects of Oral Administration of Lactobacillus acidophilus L-92 on the
Symptoms and Serum Cytokines of Atopic Dermatitis in Japanese Adults:
A Double-Blind, Randomized, Clinical Trial.
2014;165(4):247-54


Topic
What are the clinical effects of Lactobacillus acidophilus strain L-92 in a liquid milk base on perennial allergic rhinitis using a symptom severity score to evaluate improvements?

Background
Lactobacilli has been shown to be effective in many studies of atopic dermatitis (AD) in children which is a chronically relapsing inflammatory skin disease with allergic and immunological abnormalities, including increased serum IgE level, a genetic predisposition that causes a poor skin barrier and sustained antigen exposure through defective barriers, leading to Th2- dominant inflammation. Various environmental factors also contribute to the development of AD and it has been reported that intestinal inflammatory reactions and disruptions in intestinal barrier function are involved in the pathogenesis of AD. Many probiotics have been reported to have certain anti-allergic effects in humans including Lactobacillus acidophilus, L. plantarum, L. rhamnosus GG (LGG) and L. casei. Effective probiotics are believed to have immunoregulatory properties and in the case of L-92, it can mitigate the symptoms of Japanese cedar pollen allergy and perennial allergic rhinitis in children. The effect of L-92 administration on adults with AD has not been determined yet.

Study Type
Randomized, double-blind, placebo-controlled, human intervention study

Study Design
The study included 49 AD patients aged ≥16 years using heat-killed L-92. Skin lesions were assessed using the SCORing AD (SCORAD) index before L-92 ingestion and 4 and 8 weeks after. Serum cytokine and blood marker levels were measured 8 weeks after the start of L-92 ingestion. Forty-nine patients with AD (28 males and 21 females), aged ≥ 16 years, were enrolled in the study. Patients were randomly allocated to the L-92 administration group (n = 24) and the placebo group (n = 25), respectively. All patients had been treated with topical corticosteroid ointment (strong/very strongclass steroids for the body including the extremities and mild-class steroids for the face and neck) with moisturizer and one or two oral antihistamines, according to the guidelines for the symptom management of AD. The treatments were continued during the entire study period (and for 2 more weeks without changes). L-92 was administered in tablet form for 8 weeks. Placebo tablets contained maltose, starch, vegetable oil and fat. Heat-killed and dried L-92 powder was included in the L-92 tablets. SCORAD scores were used to assess the total severity and extent of eczema and subjective symptoms on pruritus and insomnia. The number of eosinophils in the peripheral blood and the levels of serum IgE, lactate dehydrogenase (LDH) and TARC, in order to reflect AD progression were also evaluated. Several cytokines were also measured before and after 8 weeks of intervention as related to the pathogenesis of AD and included IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17, eotaxin/CCL1 and interferon-γ (IFN- γ). IL-18 levels were measured using the human IL-18 ELISA kit (MBL, Nagoya, Japan). Transforming growth factor- β (TGF- β) was also measured using a different assay method.

Subjects
49 patients with atopic dermatitis

Dosage
20.7 mg/day

Results
The changes in SCORAD scores between the L-92 and placebo groups showed that seventeen patients (70.8%) showed an improvement in the L-92 group and 11 patients (44%) showed an improvement in the placebo group. The SCORAD scores were significantly reduced in the L-92 group compared with the placebo group (p < 0.01; fig. 1 a). Each component of SCORAD was significantly decreased in the L-92 group in comparison with the placebo group (p < 0.01). The eosinophil count was significantly lower in the L-92 group than in the placebo group whereas for serum IgE, LDH and TARC levels, there were no significant differences between the groups. TGF- β was significantly increased in the L-92 group compared with the placebo group (p = 0.03) and IL-12p70 also tended to be increased (p = 0.06), but no other cytokines showed significant differences. Significantly greater changes were found in the TGF- β of improved patients compared with non-improved patients (p = 0.04; fig. 4). Other cytokines measured showed no significant differences between groups.

Conclusion
The results demonstrate that L-92 is effective against AD in adults with no serious side effects observed in any of the patients. L-92 can be used as a food supplement to reduce the dose of steroidal anti-inflammatory ointments required for atopic treatment. L-92 may contribute to the suppression of Th2-dominant inflammation.