Dead Probiotics for Respiratory Health?
The Benefits of Dead Probiotics for Balanced Immune System Function and More
At this point, pretty much everyone has a basic familiarity with probiotics and the general digestive and immune benefits they may offer. Functional foods spanning far beyond the dairy industry are now enhanced with probiotics; at retail stores, we even see probiotic-enhanced snack bars, and juices. Close siblings of probiotics that many are unfamiliar with, however, are their lysed or heat-killed counterparts, which are often termed “immunobiotics” due to their immune-enhancing potential. The family of immunobiotics also includes living bacteria, but interestingly, the immune-modulating effects of heat-killed bacteria are often very similar to, or even stronger than, those of living bacteria.,,,,, Given that these bacteria are already dead, they are more resistant to degradation by digestive juices and far more commercialisable than living bacteria because they are shelf-stable and can easily be blended with other ingredients. (Something to also keep in mind when you accidentally leave your probiotics sitting on the windowsill on a sunny day!)
These heat-killed probiotic relatives are often the same species we see in probiotic blends such as Lactobacillus acidophilus, L. plantarum, or L. rhamnosus. However, rather than providing health benefits by transitionally populating the digestive tract as a probiotic would, their functionality lies in the ability of their cell wall fragments and other once-internal components or metabolites to stimulate various aspects of physiology. In addition to the heat-killed organisms, we also see research pertaining to cell-free supernatants and other purified key components;, however, the preponderant emphasis is on these heat-killed bacteria. Because they are no longer viable organisms, they have a greater safety profile than living organisms, particularly in the seriously ill or immunocompromised.,
Typically, the nonviable bacterial components have a modulating effect on immune function and tend to enhance the protective response against viral invaders.
“The cell wall fragments from lactic acid bacteria generally have been shown to enhance the Th1 immune response, simultaneously reducing the Th2 response.”
Herein, we will review the literature on two specific types of dead immunobiotics that are the topic of extensive research: heat-killed L. plantarum L-137 and L. rhamnosus lysate.
Heat-Killed Lactobacillus plantarum L-137
Numerous animal and human studies support the use of heat-killed L. plantarum L-137 (HK L-137) as a natural tool to promote a balanced immune response as well as an adequate and appropriate response against viral invaders. Some of the earliest research on HK L-137 looked at its use as an anti-allergy agent, finding that it reduced the production of immunoglobulin E (IgE) in response to the feeding of dietary antigens by increasing levels of interleukin (IL)-12. Spleen cell cultures accompanying this mouse model showed that when stimulated with HK L-137, in parallel to the increase in IL-12, there was also an increase in interferon (IFN)-γ. Although additional research further verified the ability of HK L-137 to induce IL-12, the majority of studies following this have looked at HK L-137 as an agent to improve the host defense against viral agents.
The first study showing the immune-supportive effects of HK L-137 was a randomised, double-blind, placebo-controlled trial (RDBPCT) in healthy subjects. In this study, the individuals taking HK L-137 at a dose of 10 mg daily were found to have significantly improved quality-of-life scores at eight weeks as well as a significantly greater Th1:Th2 ratio compared to controls. In certain subsets of the HK L-137 group, natural killer activity was also increased. There was also a greater percentage increase in lymphocyte counts in the HK L-137 group than in the controls, but values were still within normal ranges.
An animal study subsequent to this further investigated the mechanisms of the protective effects of HK L-137. In this study, mice were orally administered of HK L-137 for two weeks, beginning one week prior to infection with a typically fatal murine version of H1N1. In the mice given HK L-137, survival time was significantly prolonged and viral titers in the lungs were significantly lower at early stages of the infection. Of all the cytokines measured, only IFN-β—a signaling cytokine that is transmitted by virus-infected cells and that activates macrophages and induces B cells to switch immunoglobulin types—was different with the treatments, being significantly higher in the HK L-137 group in the early days after infection. A small randomized, placebo-controlled study in human subjects and another in pigs also found that intake of HK L-137 increased levels of IFN-β.
The most recent human study pertaining to the immune response considered the impact of HK L-137 on subjects with high levels of stress. Stress is a factor that can render individuals more susceptible to illness, particularly respiratory tract infections; this finding has been shown in many studies in adults and children alike.,, In this RDBPCT, subjects with high levels of psychological stress were provided with 10 mg of HK L-137 or placebo daily for 12 weeks. On a daily basis, subjects rated their symptoms of upper respiratory tract infection (URTI) using the established Wisconsin Upper Respiratory Symptom Survey-21. In the group taking HK L-137, there was a significantly lower incidence of URTIs. Additionally, URTI incidence, duration, and severity, and amount of medication use had a significant negative correlation with duration of HK L-137 use.
“In subjects with a high level of psychological stress, supplementation with 10 mg of HK L-137 daily for 12 weeks was correlated with a lower incidence of URTIs, as well as a decrease in infection duration, severity, and medication use.”
In addition to the substantial research backing the use of HK L-137 as an immune-supportive agent, this product of probiotic lysis also has human and animal data in several other settings. In humans, at a dose of 10 mg daily, HK-137 has been shown to significantly improve multiple parameters related to periodontal disease, as well as liver function tests and cholesterol balance in overweight individuals. Animal studies have additionally shown that despite HK L-137 not being a live probiotic, it still improves many aspects of digestive health including nutrient absorption, intestinal morphology, and intestinal inflammation.,,, It also has been shown in animal models to reduce cardiac complications and inflammation associated with metabolic disease.
Lactobacillus rhamnosus Lysate
There are many strains of Lactobacillus rhamnosus, with L. rhamnosus GG perhaps being the most well-known. L. rhamnosus GG has been researched for over 30 years and was the first lactobacillus strain to be patented back in 1989. L. rhamnosus GG has positive clinical data pertaining to its impact on gastrointestinal health, neuropsychiatric disorders, allergies,, and respiratory infection., Although we most often see L. rhamnosus GG advertised as a living bacteria with probiotic potential, it has also been studied and shown to have anti-inflammatory potential as a heat-killed lysate.,,
L. rhamnosus GG is only one member of a broad family within the L. rhamnosus species. In fact, there are over 100 members of the L. rhamnosus family. Many defining aspects of their genetics are largely shared, with 86.9% being the lowest shared amount with L. rhamnosus GG. That said, much like humans, there is phenotypic variation, and even strains having a 100% shared genetic fingerprint were shown to have marked differences in things as basic as sugar metabolism. Common among the L. rhamnosus family is a high level of antimicrobial activity and bile resistance, which enables them to easily colonize the gastrointestinal tract.
Certain other heat-killed strains of L. rhamnosus have also been shown to have considerable immune-modulating activity.,
In animals, both live and heat-killed L. rhamnosus have been shown to improve animal survival and reduce lung injury in influenza virus infection.
Mechanistically, they were both shown to simultaneously enhance the antiviral response and downregulate inflammation and the pro-coagulatory state, subsequently reducing lung tissue damage. In a mouse model of a pneumococcal infection, supplementation with proteoglycans from L. rhamnosus increased the number of immune responders to the lungs and significantly improved the resistance to infection. In this research, the enhanced immune response was also balanced by anti-inflammatory effects seen by the rise in IL-10.
Additional heat-killed strains of L. rhamnosus have been shown to have similar effects. Studies have shown peptidoglycans from L. rhamnosus improve resistance to respiratory syncytial virus infection and secondary pneumococcal pneumonia, also reducing inflammation-associated lung tissue injury. L. rhamnosus lysate has also shown potential in the setting of pediatric atopic eczema, safely improving quality of life and symptom scores in children ranging from eight to 64 months.
With so many probiotic strains, and their variable healing potential in both their living and heat-killed states, there is no question we will continue to see research on their immune-supportive benefits for decades to come. For now, heat-killed L. plantarum L-137 and L. rhamnosus lysate are an excellent place to start in the search for immune-enhancing natural support.
References (Fuco Immune)
 Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev. 2010 Jun;23(1):37-46.
 Villena J, et al. Immunobiotics for the prevention of bacterial and viral respiratory infections. In: Kitazawa H, et al., eds. Probiotics: Immunobiotics and Immunogenics. Boca Raton (FL): CRC Press, Taylor & Francis Group; 2013:128-68.
 Zelaya H, et al. Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation-coagulation interactions and reduces influenza virus-associated pulmonary damage. Inflamm Res. 2015 Aug;64(8):589-602.
 Villena J, et al. Enhanced immune response to pneumococcal infection in malnourished mice nasally treated with heat-killed Lactobacillus casei. Microbiol Immunol. 2009 Nov;53(11):636-46.
 Jorjão AL, et al. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7. ScientificWorldJournal. 2015;2015:716749.
 Sugahara H, et al. Differences between live and heat-killed bifidobacteria in the regulation of immune function and the intestinal environment. Benef Microbes. 2017 May 30;8(3):463-72.
 Li N, et al. Live and heat-killed Lactobacillus rhamnosus GG: effects on proinflammatory and anti-inflammatory cytokines/chemokines in gastrostomy-fed infant rats. Pediatr Res. 2009 Aug;66(2):203-7.
 Fujiki T, et al. Enhanced immunomodulatory activity and stability in simulated digestive juices of Lactobacillus plantarum L-137 by heat treatment. Biosci Biotechnol Biochem. 2012;76(5):918-22.
 Piqué N, et al. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019 May 23;20(10):2534.
 Quinteiro-Filho WM, et al. Lactobacillus and Lactobacillus cell-free culture supernatants modulate chicken macrophage activities. Res Vet Sci. 2015 Dec;103:170-5.
 Riaz Rajoka MS, et al. Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk. Food Res Int. 2019 Sep;123:286-97.
 Kubiszewska I, et al. [Lactic acid bacteria and health: are probiotics safe for human?]. Postepy Hig Med Dosw (Online). 2014 Nov 17;68:1325-34.
 Ou CC, et al. Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing the immune response toward Th1 polarization. J Food Sci. 2011 Jun-Jul;76(5):M260-7.
 Chuang L, et al. Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells. J Agric Food Chem. 2007 Dec 26;55(26):11080-6.
 Sashihara T, et al. An analysis of the effectiveness of heat-killed lactic acid bacteria in alleviating allergic diseases. J Dairy Sci. 2006 Aug;89(8):2846-55.
 Murosaki S, et al. Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol. 1998 Jul;102(1):57-64.
 Murosaki S, et al. Antitumor effect of heat-killed Lactobacillus plantarum L-137 through restoration of impaired interleukin-12 production in tumor-bearing mice. Cancer Immunol Immunother. 2000 Jun;49(3):157-64.
 Hirose Y, et al. Daily intake of heat-killed Lactobacillus plantarum L-137 augments acquired immunity in healthy adults. J Nutr. 2006 Dec;136(12):3069-73.
 Maeda N, et al. Oral administration of heat-killed Lactobacillus plantarum L-137 enhances protection against influenza virus infection by stimulation of type I interferon production in mice. Int Immunopharmacol. 2009 Aug;9(9):1122-5.
 Le Page C, et al. Interferon activation and innate immunity. Rev Immunogenet. 2000;2(3):374-86.
 Arimori 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.
 Pedersen A, et al. Influence of psychological stress on upper respiratory infection–a meta-analysis of prospective studies. Psychosom Med. 2010 Oct;72(8):823-32.
 Stover CM. Mechanisms of Stress-Mediated Modulation of Upper and Lower Respiratory Tract Infections. Adv Exp Med Biol. 2016;874:215-23.
 Drummond PD, et al. Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections. J Psychosom Res. 1997 Sep;43(3):271-8.
 Hirose Y, et al. 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 Dec 6;2:e39.
 Iwasaki 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.
 Tanaka 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. 2019 Oct 16.
 Ismaeil H, et al. Ameliorative Effect of Heat-Killed Lactobacillus plantarum L. 137 and/or Aloe vera against Colitis in Mice. Processes. 2020 Feb;8(2):225.
 Incharoen T, et al. The effects of heat-killed Lactobacillus plantarum L-137 supplementation on growth performance, intestinal morphology, and immune-related gene expression in broiler chickens. Animal Feed Sci Tech. 2019 Nov 1;257:114272.
 Dawood MA, et al. Synergetic effects of Lactobacillus plantarum and β-glucan on digestive enzyme activity, intestinal morphology, growth, fatty acid, and glucose-related gene expression of genetically improved farmed tilapia. Probiotics Antimicrob Proteins. 2019 May 11;12:389-99.
 Yang H, et al. Effects of dietary heat‐killed L actobacillus plantarum L‐137 (HK L‐137) on the growth performance, digestive enzymes and selected non‐specific immune responses in sea cucumber, A postichopus japonicus S elenka. Aquaculture Res. 2016 Sep;47(9):2814-24.
 Uchinaka A, et al. Anti-inflammatory effects of heat-killed Lactobacillus plantarum L-137 on cardiac and adipose tissue in rats with metabolic syndrome. Sci Rep. 2018 May 25;8(1):8156.
 Capurso L. Thirty Years of Lactobacillus rhamnosus GG: A Review. J Clin Gastroenterol. 2019 Mar;53 Suppl 1:S1-S41.
 Pace F, et al. Probiotics in digestive diseases: focus on Lactobacillus GG. Minerva Gastroenterol Dietol. 2015 Dec;61(4):273-92.
 Pärtty A, et al. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res. 2015 Jun;77(6):823-8.
 Durack J, et al. Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation. Nat Commun. 2018 Feb 16;9(1):707.
 Berni Canani R, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol. 2017 Jun;139(6):1906-1913.e4.
 Kumpu M, et al. The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care. J Med Virol. 2013 Sep;85(9):1632-8.
 Kumpu M, et al. Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2012 Sep;66(9):1020-3.
 Zhang L, et al. Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-alpha-induced interleukin-8 production in Caco-2 cells. J Nutr. 2005 Jul;135(7):1752-6.
 Lopez M, et al. Live and ultraviolet-inactivated Lactobacillus rhamnosus GG decrease flagellin-induced interleukin-8 production in Caco-2 cells. J Nutr. 2008 Nov;138(11):2264-8.
 Douillard FP, et al. Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG. PLoS Genet. 2013;9(8):e1003683.
 Kolling Y, et al. Non-viable immunobiotic Lactobacillus rhamnosus CRL1505 and its peptidoglycan improve systemic and respiratory innate immune response during recovery of immunocompromised-malnourished mice. Int Immunopharmacol. 2015 Apr;25(2):474-84.
 Kolling Y, et al. Are the immunomodulatory properties of Lactobacillus rhamnosus CRL1505 peptidoglycan common for all Lactobacilli during respiratory infection in malnourished mice? PLoS One. 2018 Mar 8;13(3):e0194034.
 Clua P, et al. Peptidoglycan from Immunobiotic Lactobacillus rhamnosus Improves Resistance of Infant Mice to Respiratory Syncytial Viral Infection and Secondary Pneumococcal Pneumonia. Front Immunol. 2017 Aug 10;8:948.
 Hoang BX, et al. Lactobacillus rhamnosus cell lysate in the management of resistant childhood atopic eczema. Inflamm Allergy Drug Targets. 2010 Jul;9(3):192-6.
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