References

● Mechanisms to relieve allergies

1.Y. Ishida et al.: Decrease in ovalbumin specific IgE of mice serum after oral uptake of lactic acid bacteria. Biosci Biotechnol Biochem., 67, 951-957(2003)

Abstract

Different kinds of lactobacilli and Bifidobacteria fermented milk were fed to ovalbumin-specific IgE-elevated mice for 3 days, and after the final administration, changes in the ovalbumin-specific IgE values for each sample were compared to the value for non-fermented milk. Seven of the Lactobacillus-fermented milks caused a significant decrease in the serum ovalbumin-specific IgE levels. Above all, Lactobacillus acidophilus L92, Lactobacillus acidophilus CP1613, and Lactobacillus fermentum CP34 fermented milk had the most significant effects of decreasing the serum ovalbumin-specific IgE levels compared to a control group. The L. acidophilus L92 and L. fermentum CP34 cells also showed significant ovalbumin-specific IgE lowering activities. From these results, an active component seems to exist in the cells of L. acidophilus L92 and L. fermentum CP34 strains. Recovery of the radiolabeled L. acidophilus L92 and L. fermentum CP34 cells from the small intestine and the large intestine of the mouse 13 h after oral administration were higher than the recovery of any other strain.

2.H. Kanzato et al.: Lactobacillus acidophilus L-92 induces apoptosis of antigen-stimulated T cells by modulating dendritic cell function. Immunobiology., 213, 399 (2008)

Abstract

Beneficial effects of lactobacilli have been reported for patients with allergic diseases and intestinal disorders such as inflammatory bowel disease. However, it is not fully understood how such bacteria influence the immunologic response. For this purpose, we investigated the effect of Lactobacillus acidophilus strain L-92 (L-92) on antigen-stimulated T cell responses in vitro and in vivo. In vitro, L-92 decreased the proliferation of CD4(+) T cells stimulated with antigen, and also induced apoptosis of antigen-stimulated T cells. On the other hand, interferon (IFN)-gamma secretion from naïve T cells was increased while interleukin (IL)-4 secretion was decreased by L-92. Co-culture with L-92 induced apoptosis of differentiated Th1 and Th2 cells. The degree of apoptosis induction was higher in Th2 cells. Moreover, L-92 up-regulated the expression of B7-H1 and down-regulated that of B7-H2 on dendritic cells (DCs), and DCs exposed to L-92 also induced apoptosis of antigen-stimulated T cells. Finally, orally administered L-92 induced apoptosis of OVA-specific TCR Tg T cells. These results indicate that L-92 attenuates the CD4(+) T cell response by inducing DC-mediated apoptosis and that it might exert beneficial effects in patients with diseases resulting from a hyper-response of CD4(+) T cells.

3.A. Torii et al.: Lactobacillus acidophilus L-92 regulates the production of Th1 cytokines as well as Th2 cytokines. Allergol. Int., 56,293 (2007)

Abstract

BACKGROUND:
There is growing interest in probiotics such as lactic acid bacteria (LAB), not only for treatment of T helper type (Th) 1-mediated diseases but also for Th2-mediated diseases, including allergic diseases, since lactic acid bacteria may be able to modulate the Th1/Th2 balance, in addition to having an immunomodulative effect through induction of Th1 bias.
METHODS:
The effect of oral administration of heat-killed Lactobacillus acidophilus strain L-92 (L-92) on ovalbumin (OVA)-specific immunoglobulin (Ig)E production was investigated in BALB/c mice. L-92 was orally administered to mice for 8 weeks from 2 weeks after initiation of OVA-immunization. Patterns of cytokine and Ig production in splenocytes and cells from Peyer's patches (PPs) from these mice were examined after restimulation with OVA in vitro.
RESULTS:
L-92 significantly suppressed serum OVA-specific IgE levels for a long period. Cytokines such as interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 and Igs such as total IgE and OVA-specific IgE were produced at significantly lower levels by splenocytes of L-92-treated mice, compared with those of control mice. In contrast, transforming growth factor (TGF)-beta and IgA levels produced by PPs from L-92-treated mice were significantly higher than in those from control mice.
CONCLUSIONS:
Oral L-92 administration regulated both Th1 and Th2 cytokine responses, suppressed serum OVA-specific IgE, and induced TGF-beta production in PPs. TGF-beta is known to be associated with activation of regulatory T (Treg) cells. These data suggest that LAB may have immunomodulative effect by Treg cells via TGF-beta activity.

4.M. M. Shar et al.: Lactobacillus acidophilus L-92 induces CD4(+)CD25(+)Foxp3(+) regulatory T cells and suppresses allergic contact dermatitis. Biol Pharm Bull.,35(4), 612-6(2012)

Abstract

The anti-allergic mechanism of heat-killed Lactobacillus acidophilus strain L-92 has not been fully investigated. Recent studies have reported that CD4(+)CD25(+)Foxp3(+) (forkhead box P3) T regulatory (Treg) cells play important roles in controlling allergic diseases. Hence, we examined the effect of orally administered L-92 on CD4(+)CD25(+)Foxp3(+) cell populations. BALB/c mice were supplemented daily with L-92 by gavage for 5 weeks. 2,4-Dinitrofluorobenzene (DNFB) was used to induce allergic contact dermatitis (ACD) in mice. Fluorescent-activated cell sorter (FACS) analysis was used to determine CD4(+)CD25(+)Foxp3(+) T cell populations in spleen and cervical lymph nodes (CLN). Interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and Foxp3 mRNA expressions in mouse ear skin were investigated by real-time reverse transcription-polymerase chain reaction (RT-PCR). The percentage of CD4(+)CD25(+)Foxp3(+) T cell populations were significantly increased in both spleen and CLN of L-92-fed group than vehicle and control. In addition, L-92 produced higher levels of Foxp3, IL-10 and TGF-β compared to control mice. These results suggest that L-92 can up-regulate the number of Treg cells to suppress the progression of DNFB-induced contact dermatitis in mice.

● Effects on relieving hay fever

5.Y. Ishida et al.: Effect of Milk Fermented with Lactobacillus acidophilus L-92 on Symptoms of Japanese Ceder Pollen Allergy: A Randomized Placebo-Controlled Trial. Biosci Biotechnol Biochem., 69, 1652-1660 (2005)

Abstract

A placebo-controlled, single-blind study was conducted to evaluate the effects of Lactobacillus acidophilus strain L-92 (L-92) on the symptoms of Japanese cedar-pollen allergy. This study was carried out during the 2002 and 2003 seasons of Japanese cedar pollination. Twenty-three in-house volunteers were asked to drink 100 ml of heat-treated milk fermented with L-92 containing 5 x 10(10) of the bacteria, twice a day, for 6 consecutive weeks. A similar study was carried out during the 2003 season for 10 weeks, but the daily dose of bacteria was 2 x 10(10). A significant improvement of the ocular symptom-medication score (SMS) was observed in 2002 and of the score of distress of life in 2003. These data show that a daily oral intake of not less than 2 x 10(10) heat-treated L-92 cells improved the symptoms of Japanese cedar pollinosis, thereby contributing to reduce the dose of concomitant medications. However, no blood parameter was significantly affected in these trials.

6.H. Kanzato: Effects of the Lactobacillus acidophilus strain L-92 on hay fever. Medical Science Digest, 35,27-30 (2009)

7.M. Enomoto et al.: Effects of oral consumption of the Lactobacillus acidophilus L-92 in cedar pollen hay fever – Tests on preventive effects at an artificial exposure facility. Key Note Speeches from the 56th Fall Meeting of the Japanese Society of Allergology (2006)

Abstract

[Details published]
[Objectives]
A cedar pollen allergy provocation test was conducted in an artificial exposure facility with the objective of verifying the preventive effects of oral administration of L.acidophilus L-92 strains against cedar pollen allergy.
[Method]
Volunteers were divided into four groups including the placebo group (21 volunteers), 20 mg group (21), 60 mg group (22) and 180 mg group (20). The groups were uniform in terms of the severity of cedar pollen allergy. After an 8-week intake of test food, the volunteers were subjected to a second exposure to cedar pollen (10000/m³). We analyzed changes in the subjective symptoms they experienced in the exposure room and after leaving it. Their nasal mucosa findings and blood analysis values determined right after exposure were also analyzed.
[Results]
For the subjective symptoms experienced in the exposure room, itching of eyes and nose and nasal congestion were significantly alleviated. TARC found a dose-dependent tendency toward the inhibition of elevation. For subjective symptoms experienced after leaving the exposure room, itching of eyes and nose was significantly alleviated.
[Conclusion]
The oral administration of the strains suggested dose-dependent preventive effects against cedar pollen allergy.

● Effects on relieving perennial allergic rhinitis

8.Y. Ishida et al.: Clinical Effects of Lactobacillus acidophilus L-92 on Perennial Allergic Rhinitis: A Double-Blind, Placebo-Controlled Study. J.Dairy Science, 88, 527-533 (2005)

Abstract

Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases, however, little information is available on their clinical effect on allergy in humans. Thus, we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 (L-92) on perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis were randomized to receive either 100 mL of heat-treated fermented milk containing L-92 (n = 25) or acidified milk without lactic acid bacteria (placebo; n = 24) for 8 wk. The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms. Oral administration of milk fermented with L-92 resulted in a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group. In addition, clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk. There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1 / T helper type 2 ratio between the 2 groups. These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis, however, statistically significant changes were not shown in blood parameters.

● Effects on relieving atopic dermatitis

9.S. Torii et al.: Effects of Oral Administration of Lactobacillus acidophilus L-92 on the Symptoms and Serum Markers of Atopic Dermatitis in Children. Int. Arch. Allergy Immunol., 154, 236-245 (2011)

Abstract

BACKGROUND:
Few studies have investigated the complementary effects of long-term oral administration of Lactobacillus acidophilus on traditional medical therapy in the treatment of patients with atopic dermatitis (AD).
METHODS:
The Atopic Dermatitis Area and Severity Index was used to evaluate AD severity. Symptom severity was assessed using the symptom score. The effect of medical therapy was evaluated by adding the medication score, calculated as the sum of each product of the amount of steroid ointment used for therapy and its designated strength graded on a 4-point scale, to the symptom score. The complementary effect of long-term oral administration of L. acidophilus strain L-92 (L-92) as a probiotic or biogenic strain in patients with AD was evaluated using the symptom-medication score, which was calculated as the sum of the symptom score and medication score. Both a preliminary casuistic study and a double-blinded, placebo-controlled study were performed to evaluate the effects of L-92 on the symptoms of AD in children.
RESULTS:
Orally administered L-92 significantly ameliorated the symptoms of AD in Japanese children. L-92 also affected the serum concentrations of thymus and activation-regulated chemokine in a time-dependent manner.
CONCLUSIONS:
The results of the preliminary trial and the double-blinded, placebo-controlled study revealed a complementary effect of oral L-92 on the standard medical therapy (topical application of a steroid ointment) in patients with AD that was mediated, at least in part, by alterations in the Th1/Th2 balance.

10.M. Hatanaka et al.: Effects of the Lactobacillus acidophilus L-92 as an assistive treatment for infant atopic dermatitis. 2nd Annual Meeting of the Japan Association for Food Immunology (2006)

● Effects on preventing influenza infection

11.H. Goto et al.: Anti-influenza virus effects of both live and non-live Lactobacillus acidophilus L-92 accompanied by the activation of innate immunity. Br. J. Nutr., 110.1810-1818 (2013)

Abstract

The antiviral effects of both a live and non-live Lactobacillus acidophilus strain L-92 (L-92) were investigated by oral administration (10 mg/mouse per d) daily for 21 d in a mouse model infected intranasally with influenza virus (H1N1). Virus titres in the lung of mice administered either live or non-live L-92 cells daily for 15 d were repressed 6 d after virus infection compared with the control group. Natural killer (NK) activity in the orally administered non-live L-92 group was higher compared with that of the control group before virus infection and on day 6. In contrast, NK activity in the live L-92 group compared with the control group was not significantly changed on both days, but was significantly higher on day 1. In contrast, live L-92 showed a greater repression of virus proliferation compared with non-live L-92, 6 d after the infection. Live L-92 decreased the number of neutrophils in the lung and suppressed lung weight, leading to the consequent deterioration of consolidation scores of the lung. These results indicated that pretreatment of live or non-live L-92 cells had protective effects against influenza virus infection. Among the measured cytokines and chemokines, eotaxin, macrophage colony-stimulating factor, IL-1b, RANTES (regulated on activation, normal T cell expressed and secreted) and interferon-a were significantly increased in the lung: IL-17 was significantly increased in Peyer’s patch of the live L-92 group compared with the control group. A mechanistic study suggested that the enhancement of NK activity in the lung caused by stimulating various antiviral cytokines and chemokines after the oral administration of L-92 cells might be important in protecting against virus infection.

12.Y. Inoue 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. Int.Arch.Allergy Immunol.,165(4),247-54(2014)

Abstract

OBJECTIVES:
Several studies on lactobacilli have demonstrated they are effective against atopic dermatitis (AD) in children, but there are very few reports of their effects in adults. We investigated the changes in AD symptoms in adults after the ingestion of the Lactobacillus acidophilus strain L-92 (L-92), which has been shown to have a curative effect on AD in children.
METHODS:
A double-blind, parallel-group, placebo-controlled comparison was performed on 49 AD patients aged ≥16 years using heat-killed L-92. Skin lesions were assessed using the SCORing AD (SCORAD) index before the start of L-92 ingestion and 4 and 8 weeks after ingestion. Serum cytokine and blood marker levels were measured 8 weeks after the start of L-92 ingestion.
RESULTS:
The group that ingested L-92 had lower SCORAD scores than the controls (p = 0.002). The L-92 group also had decreased ratios of change for eosinophil count (p = 0.03) and increased ratios of change for serum TGF-β (p = 0.03). Ratios of change for serum TGF-β rose significantly (p = 0.04) in patients showing mitigated symptoms with L-92 administration.
CONCLUSIONS:
Administration of heat-killed L-92 was effective for AD symptoms in adults. L-92 may contribute to the suppression of Th2-dominant inflammation. Our preliminary trial is the first to report the effects of L-92 on adult AD.