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A Lactobacillus plantarum Postbiotic for Immunity

Lactobacillus plantarum Lactobacillus plantarum
EuroMedica
 
Longevity By Nature

Most people in the natural products industry are familiar with probiotics and prebiotics, but not everyone is familiar with postbiotics. The focus of this article is on one particular postbiotic derived from Lactobacillus plantarum. Before getting into it, however, let’s first answer the following question.

What Is a Postbiotic?

Probiotics are friendly bacteria that confer a health benefit when consumed, generally by improving or restoring the gut flora. These include, but are not limited to, friendly bacteria in the lactobacillus, bifidobacterium and bacillus genus. Prebiotics are specialized plant fibers that act as food for the friendly bacteria. These include, but are not limited to, fructooligosaccharides, galactooligosaccharides and xylooligosaccharides. But postbiotics are something else entirely.

Depending upon your preferred definition, a postbiotic may be one of two things. The first is a metabolite produced by a probiotic. For example, many probiotics produce the short-chain fatty acid butyric acid or butyrate—this would be one of several metabolite-type postbiotics. The second is a thermal-treated probiotic that is no longer alive, but still confers a beneficial effect—a sort of zombie probiotic if you will. To my mind, both definitions are legitimate, but in this article, I’ll be discussing a postbiotic based on the second definition. In this case, the postbiotic is commercially known as Immuno-LP20 (by Mitsubishi)—okay, actually Immuno-LP20 contains 20 percent of the thermal-treated Lactobacillus plantarum strain L-137 (HK L-137) and 80 percent of dextrin. In any case, 50 mg of Immuno-LP20 provides 10 mg of HK L-137, which is the amount used in all of the studies I’ll be discussing. Since using two different names can be a little bit confusing, I’m just going to refer to the postbiotic as Immuno-LP20 in the studies discussed.

Augmentation of Acquired Immunity

A 12-week, randomized, double-blind, placebo-controlled, parallel study1 was conducted in 60 healthy subjects (30 men and 30 women, mean age 56.3 y) to determine whether the intake of Immuno-LP20 influences immune function and the quality of life (QOL). Subjects were randomly assigned to receive a capsule containing Immuno-LP20 or a matching capsule. Biomarkers for innate immunity such as the natural killer activity of peripheral blood mononuclear cells, neutrophil phagocytosis and cell surface expression of CD64 on monocytes were measured every four weeks. Biomarkers for acquired immunity such as concanavalin A (Con A)-induced proliferation, percentages of INF-g and IL-4–producing cluster of differentiation (CD)4+ T cells (Th1:Th2 ratio), and the serum IgG4:IgG ratio were measured every four weeks or at wk 0 and wk 12. Health-related QOL was assessed using a self-rating questionnaire with 26 items. Among the measured biomarkers, the percent change in Con A-induced proliferation and the Th1:Th2 ratio in the Immuno-LP20 group was greater than those in the control group (P = 0.036 and P = 0.002, respectively). The degree of improvement in QOL was higher in the Immuno-LP20 group than in the control group at weeks 8 (P = 0.049) and tended to be higher at weeks 12 (P = 0.092). These results suggest that a daily intake of Immuno-LP20 augments acquired immunity, especially Th1-related immune functions in healthy subjects, thereby improving the health-related QOL.

Stimulate Interferon With an Influenza Vaccine Study

A study2 was conducted to examine the potential of Immuno-LP20 intake to stimulate type I interferon (IFN) on type I IFN in humans given an influenza vaccine (which has also been shown to augment host defense against influenza A virus infection in mice). Sixteen subjects were randomly assigned to receive a tablet containing Immuno-LP20 or a matching tablet for eight weeks and the serum levels of type I IFN were examined before and after the first or second dose of the trivalent inactivated influenza vaccine. Results were that the levels of IFN-β were significantly higher in the Immuno-LP20 group than in the control group before vaccination, although the vaccination conferred little additional induction of IFN-β. In addition, researchers further examined IFN-β gene expression in the whole blood cells of pigs fed on a diet containing Immuno-LP20 and found that the IFN-β mRNA levels were significantly higher in the Immuno-LP20 group than in the control group. The finding that daily intake of Immuno-LP20 enhances type I IFN production and host defense against influenza A virus infection in mice may be applied to at least two additional species, including humans.

Upper Respiratory Tract Infection Study

A 12-week, randomized, double-blind, placebo-controlled, parallel study3 was conducted to assess the effects of Immuno-LP20 on upper respiratory tract infection (URTI) symptoms in 78 healthy subjects (33 men and 45 women; mean age 50.6 years) with high psychological stress levels. The URTI symptoms were rated once daily with a scientifically validated questionnaire, and cellular immune functions were measured every four weeks. Results were that URTI incidence was significantly lower in the Immuno-LP20 group than in the placebo group. URTI incidence, duration and severity, and duration of medication showed significant negative correlations with duration of Immuno-LP20 intake. The percentage change from baseline of cellular immune functions was significantly greater in the Immuno-LP20 group than in the control group. These findings suggest that daily Immuno-LP20 intake can decrease URTI incidence in healthy subjects, likely through augmentation of immunity.

Periodontal Therapy Support

This 12-week, randomized, double-blind, placebo-controlled clinical trial4 was conducted to examine the effects of the oral administration of Immuno-LP20 on the outcome of periodontal therapy in 39 patients. Patients undergoing supportive periodontal therapy (SPT) were randomly assigned to receive a capsule containing Immuno-LP20 or a placebo capsule daily. Nineteen patients in the experimental group and 17 patients in the control group were followed-up. Clinical parameters, including plaque index (PI), gingival index (GI), bleeding on probing (BOP) and probing depth (PD) were scored at baseline and weeks 4, 8 and 12 prior to prophylaxis in conjunction with regular SPT visits. Results were that BOP and the number of teeth or sites with PD ≥ 4 mm were significantly reduced in both groups by a successive SPT program, while there was significantly greater PD reduction (p < 0.05) at teeth with site(s) with PD ≥ 4 mm at baseline in the Immuno-LP20 group than in the placebo group at week 12. These clinical findings suggest that daily Immuno-LP20 intake can decrease the depth of periodontal pockets in patients undergoing supportive periodontal therapy.

Inflammation and Lipid Metabolism Study

A 12-week, randomized, double-blind, placebo-controlled, parallel group study5 was conducted to investigate the effects of Immuno-LP20 on inflammation and lipid metabolism in 100 healthy overweight volunteers with a body mass index from 23.0 to 29.9 (51 men and 49 women; mean age: 41.4 years). Subjects were randomly assigned to daily administration of a tablet containing Immuno-LP20 or a placebo tablet for 12 weeks. Blood samples were collected every four weeks to measure biomarkers of lipid metabolism and inflammatory mediators. Results were that daily intake of Immuno-LP20 improved inflammation (e.g. aspartate transaminase (AST) and alanine aminotransferase (ALT) decrease) and lipid metabolism (including decreases of total cholesterol, and LDL cholesterol) in subjects at risk of inflammation.

Safety Study

In addition to studies demonstrating the efficacy of Immuno-LP20, research has also shown it to have a good safety profile as well. A four-week study6 was conducted to investigate the high-dose and long-term use effects of Immuno-LP20 on immune-related safety and on host intestinal bacterial flora of 15 healthy volunteers. An additional 29 participants who regularly visited a clinic for health care took Immuno-LP20 daily for 12 months. Measures for anthropometrics, hematology, biochemistry and urinalysis were taken at scheduled timepoints for all participants. Stool and blood samples were also collected and evaluated for microbes and short-chain fatty acids (SCFA); isolated T-cells were assessed for levels of proliferation induced by phytohemagglutinin in the long-term study. Results were that there were no observed adverse events or shifts in clinical measures from normal ranges in the high-dose or long-term studies. Long-term intake also did not result in immune exhaustion due to any chronic immunostimulation. Also, T-cell proliferation was significantly greater at 12 months than at baseline (p < 0.01). In addition, the probiotic balance in stool samples was significantly lower at 12 months than at baseline (p < 0.05) due to the long-term intake of the Immuno-LP20, an indication of maintaining normal intestinal homeostasis. Lastly, fecal short-chain fatty acid concentrations (which you may remember is a metabolite-type postbiotic) were significantly greater (p < 0.05) at six months than at baseline. From these data, it can be concluded that the efficacy of Immuno-LP20 is maintained with no overt adverse effects as a result of high-dose and/or long-term consumption.

Postbiotic Advantages

One of the chief advantages of a postbiotic is stability. Since it’s not a live microorganism, you don’t need to worry about it being destroyed by heat, stomach acid or other common causes of probiotic destruction. Furthermore, unlike many common probiotics that don’t tend to play well with other nutraceuticals in a formulation, postbiotics can be combined with just about anything else without any ill effect to the postbiotic. If you are a supplement formulator, like me, these two features make probiotics desirable to formulate with.

Conclusion

Immuno-LP20 is a postbiotic derived from Lactobacillus plantarum. Human clinical research indicates that this postbiotic helps augment acquired immunity, stimulate interferon in association with an influenza vaccine, reduce upper respiratory tract infection incidence, duration and severity, improve outcomes in periodontal therapy, and reduce inflammation while improving lipid metabolism. Furthermore, Immuno-LP20 achieves these benefits with a good safety profile.

References:

1 Hirose Y, Murosaki S, Yamamoto Y, et al. Daily Intake of Heat-Killed Lactobacillus plantarum L-137 Augments Acquired Immunity in Healthy Adults. J Nutr. 2006; 136: 3069–3073.

2 Arimori Y, Nakamura R, Hirose Y, et al. Daily intake of heat-killed Lactobacillus plantarum L-137 enhances type I interferon production in healthy humans and pigs. Immunopharmacol Immunotoxicol. 2012 Dec;34(6):937-43.

3 Hirose Y, Yamamoto Y, Yoshikai Y, Murosaki S. Oral intake of heat-killed Lactobacillus plantarum L-137 decreases the incidence of upper respiratory tract infection in healthy subjects with high levels of psychological stress. J Nutr Sci. 2013; 2: e39.

4 Iwasaki K, Maeda K, Hidaka K, et al. Daily Intake of Heat-killed Lactobacillus plantarum L-137 Decreases the Probing Depth in Patients Undergoing Supportive Periodontal Therapy. Oral Health Prev Dent. 2016;14(3):207-14.

5 Tanaka Y, Hirose Y, Yamamoto Y, et al. Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial. Eur J Nutr. 2020 Sep;59(6):2641-2649.

6 Nakai H, Murosaki S, Yamamoto Y, et al. Safety and efficacy of using heat-killed Lactobacillus plantarum L-137: High-dose and long-term use effects on immune-related safety and intestinal bacterial flora. J Immunotoxicol. 2021 Dec;18(1):127-135.

Gene Bruno, MS, MHS, the provost for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 40 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gene.bruno@hchs.edu.