Immunobiotics – enhancing human immunity

The rise and fall of the antibiotic

Once hailed as the wonder drug for eradicating infectious bacterial diseases, the antibiotic has long since lost its shine. There is an increasing awareness that, although millions of lives in the past have been saved, antibiotics have been overused and are now responsible for numerous adverse effects. Such effects include the development of antibiotic-resistant bacteria, the erosion of the protective mucous lining of the intestines and major destruction of the ‘friendly’ microbiota that are essential for human health.1

Targeting the Gut-Immune Interface

As a Nutritional Biochemist with a profound interest in clinical Nutrigenomics, I have been conscious of the need to find antibiotic alternatives that are capable of both preventing and treating infectious disease. I am especially interested in solutions that mimic the way in which Nature herself maintains such protection.

Our company already produces the most potent sulforaphane-yielding broccoli sprout ingredient, remarkable in that it mimics the way in which Nature addresses cellular defence processes; however, we wanted to identify a specific immune-enhancing ingredient to complement it. What we were looking for was something to target the Gut-Immune interface. Under-appreciated is the fact that around 80% of human immune activity occurs just below the single layer of cells lining the gut. This meant that we were looking for a food-derived molecule capable of activating the immune signalling mechanisms that are naturally present in the gut wall.

Finding an Immunobiotic Solution

After extensively researching the topic, I discovered some Japanese studies that really caught my attention. The group had investigated a particular strain of Lactobacillus plantarum, a well-known probiotic bacterium that is available in probiotic supplements but also abundant in cultured foods like kefir, sauerkraut and kimchi. The strain the Japanese group used in their research was obtained from a fermented fish and vegetable dish popular in the Philippines.

As I read, I discovered that not only had they investigated the mechanisms of action of this Lactobacillus strain, but they had also published several impressive clinical trials associated with various aspects of immunity. More importantly, the exact nature of the strain they used completely turned upside down some of our ingrained thinking about probiotics.

Wanted Dead or Alive: Lactobacillus plantarum HKL-137

For decades, we’ve been accustomed to ingesting live probiotic organisms that must be refrigerated to retain their viability. So, it came as a huge surprise to find that ‘HKL’ stands for ‘Heat-Killed Lactobacillus’. These bacteria are grown until their activity and their number are maximised – and then they are killed by the application of heat, the very thing we thought would make them useless!

Of course, I wondered how this could work, until I realised that its mechanism mimics the processes used by Nature, exactly what we were looking for. The cell wall of HKL-137, like that of other Gram-positive bacteria, contains a specialised molecule, lipoteichoic acid (LTA). Specialised receptors on the surface of the intestinal lining cells recognise LTA and trigger a series of signals that ‘tell’ the neighbouring immune network to activate its immune defences.

How HKL-137 led us to new product development

The focus of our company, Cell-Logic is primarily on developing demonstrably effective formulations for clinicians specialising in Nutritional Medicine and Nutrigenomics and then to provide in-depth professional education to support our formulations.

HKL-137 was clearly a perfect fit for our new clinical gut health programme, Gut Ecology & Metabolic Modulation Protocol (G.E.M.M.), a system designed to prevent and treat disease via the gut-immune interface. It was already known that Lactobacillus plantarum was capable of improving the gut barrier and reducing intestinal permeability, a key factor in promoting food intolerance. The knowledge that HKL-137 yields a stable and measurable source of LTA provided us with the confidence to assume that it would likely assist the sulforaphane which is the foundation to the high-potency formulations we use to enhance the activity of the gut-immune interface.

Even though our primary focus is on educating clinicians on the G.E.M.M. Protocol, HKL-137 showed such promise that we wanted to make it also available to consumers. Better still, HKL-137 has a long shelf-life and is both heat-stable and acid-stable, three clear advantages over a live probiotic supplement.

ImmunoGenex, is our powdered formula version available to the retail market. ImmunoGenex is a pleasant-tasting formulation containing only natural ingredients and which can be stirred into water, juice or milk. ImmunoGenex is designed to be taken in conjunction with our sulforaphane-yielding DefenCell for optimum support for the Gut-Immune interface.

Several years of clinician and patient response has providing us with the kind of feedback we were hoping for – and often in patients who have ‘tried everything else’ without success. In addition to its enhancement of both innate and acquired immunity, HKL-137 can down-regulate inflammation and reduce allergic tendencies and food intolerance reactions. Most importantly, it utilises the naturally occurring mechanisms of human cells to influence the immune response.

Clinical Trial Data on HK L-137

In a 2006 study, Japanese researchers wanted to know if HKL-137 was able to enhance acquired immunity. In the 3-month study of 60 healthy adults, they were able to confirm that the effect was positive, with measurable enhancement in quality of life. A later study in 2013 investigated the incidence of upper respiratory infection in healthy, stressed adults and found that there was a significant reduction in the number of colds these individuals experienced.2

A number of other HKL-137 studies in animals and humans have been conducted with yet more in progress. A recent study on dental health indicates HKL-137’s broad application. In 2016, it was found that HKL-137 can benefit those with periodontal disease. It was shown that the probing depth of periodontal pockets significantly decreased in patients undergoing supportive periodontal therapy.3 More recently in 2018, two studies showed that the LTA from L. plantarum inhibits the formation of plaque-forming biofilms due to overgrowth of decay-forming bacteria.4,5

Move over Vitamin C

For decades, it has been assumed that higher than dietary levels of vitamin C is the supplement of choice for immune enhancement and antioxidant support. However, when one considers that the gut-immune interface plays such a key role in mounting an immune response, it is difficult to see how vitamin C can fit into our newer understanding of how human cells defend themselves against infection. This is where HKL-137 takes centre stage.

Similarly, when it is realised that cells make their own antioxidants nutrigenomically in the form of glutathione and the antioxidant enzymes, it becomes clear that the megadoses of Vitamin C that have been recommended in the past do not mimic the methods used by Mother Nature in restoring and maintaining health.

Moving forward

By providing clinicians with the most up-to-date professional education and well-researched formulations to support the science, Cell-Logic aims to remain a leader in the fields of Nutrigenomics and Nutritional Medicine. Already acknowledged as a global leader in the field of Nutrigenomics,6 we are known for our willingness to challenge outdated and flawed paradigms, appropriately changing our clinical recommendations as the science evolves.

Australians are eager consumers of evidence-based nutraceutical supplements and Cell-Logic takes pride in delivering clinically-effective solutions. HKL-137 is an excellent example of an ingredient that mimics Nature’s approach to the prevention and management of infectious disease, allergy and unresolved inflammation. As such, it meshes perfectly with the Cell-Logic philosophy.

Christine Houghton PhD.,BSc.,R.Nutr.
Nutritional Biochemist
18th April, 2019

REFERENCES

1. Yoon MY, Yoon SS. Disruption of the Gut Ecosystem by Antibiotics. Yonsei medical journal. 2018;59(1):4-12.
   2. 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.
   3. Iwasaki K, Maeda K, Hidaka K, Nemoto K, Hirose Y, Deguchi S. Daily Intake of Heat-killed Lactobacillus plantarum L-137 Decreases the Probing Depth in Patients Undergoing Supportive Periodontal Therapy. Oral health & preventive dentistry. 2016;14(3):207-214.
   4. Ahn KB, Baik JE, Yun CH, Han SH. Lipoteichoic Acid Inhibits Staphylococcus aureus Biofilm Formation. Front Microbiol. 2018;9:327.
   5. Ahn KB, Baik JE, Park OJ, Yun CH, Han SH. Lactobacillus plantarum lipoteichoic acid inhibits biofilm formation of Streptococcus mutans. PLoS One. 2018;13(2):e0192694.
   6. Wood L. Global Nutrigenomics Market by Application and Region – Forecast to 2025. https://www.businesswire.com/news/home/20190306005326/en/Global-Nutrigenomics-Market-Application-Region—Forecast 6th March, 2019.