Overuse of antibiotics is causing concern at the highest levels of the government. Eighty percent of antibiotics are used in industrial agriculture for cows, pigs and poultry. With the emergence of antibiotic-resistant bacteria, the calls for something to replace antibiotics in livestock (not to mention humans) have become more urgent.
I have discovered that the harmless food bacteria, Lactobacillus caseii, a bacterium typically found in milk, releases immune-modulating molecules when entering the mouth, which protect animals and humans from viral infections. The paradigm-setting discovery was made years ago, but is only now finding acceptance. It may lead us to something more effective and more natural than modern antibiotics.
As associate professor of microbiology and immunology at the New York Medical College (NYMC) in the 1990s, I found that all fifteen tested bacteria, whether harmless or harmful, immediately released pieces of ribonucleic acid (RNA) when exposed to human saliva. At first I thought the bacteria were being killed by salivary enzymes and the small pieces of RNA were simply debris from dying cells. However, after exposure and transfer into growth media, the bacteria grew more vigorously.
What was going on here? Why would bacteria, especially the harmful ones, give the host a heads-up as to their appearance? Although brainless, they have lots of smarts gained through eons of co-evolutionary life with us. Logically, releasing these small pieces of RNA must be improving their advantage. And that’s exactly how it turned out: by releasing them, the bacteria were able to ramp up their offenses for a fight. But even the harmless ones were arming themselves for a fight. The small pieces of RNA, called oligoribonucleotides or ORNs, looked to be identical from all of the fifteen studied bacteria. Were they toxic? I purified them and with two colleagues, Michael Hoffmann and Zhi Qin Wang, fed and injected them into young mice. We didn’t see any ill effects; their lifestyles weren’t altered. Feeding or injecting the ORNs simply had no observable effects.
Although I studied all fifteen, I focused on L. caseii, a harmless strain commonly occurring in milk. Known simply as a harmless strain, I thought it might actually be beneficial. Maybe during countless eons of co-evolution, our immune system adapted a combat-ready response to the appearance of harmless bacteria as well as the harmful ones. Perhaps the sentry cells of the immune system weren’t distinguishing friend from foe at this point. But how good was its combat-ready response? It was a testable question.
Commercial LPS (lipopolysaccharide) is a component of bacterial outer membranes that is often used to test the strength of an immune system. Feeding high doses of LPS to mice induces lethal septic shock. I decided to feed the ORNs released by L. caseii to mice and then inject them with a lethal dose of LPS. Surprisingly, all the mice receiving the ORNs thirty hours before the LPS injection survived and returned to full health. Those not fed the ORNs beforehand died in two days. The lethality of septic shock is believed to result from an immune system gone berserk, running out of control, punching holes in internal tissues looking for the intruder. Somehow feeding the ORNs from L. caseii beforehand had restored a stable immune condition, preventing it from becoming violently self-destructive when injected with LPS.
To learn more, Carl Hamby, a faculty colleague and I developed a molecular and cellular test using immune cells from human blood. First, Carl exposed the cells from donors’ blood to ORNs from L. caseii and saw them release a small amount of a cytokine known to produce inflammation. Inflammation is key to fighting infection, but too much can lead to disease, septic shock and death. The ORNs temporarily induced a low degree of inflammation, a good sign, suggesting that it was primed for a fight.
However, exposing immune cells to LPS induced a massive amount of the inflammatory cytokine to be released. If the immune cells were first exposed to the ORNs, as we had done in the mouse experiment, much lower amounts of the inflammation-inducing cytokine were released. The ORNs administered thirty hours before LPS prevented the runaway inflammatory response, just what we had seen in mice.
Finding protection against septic shock death was amazing. But what else could feeding L. caseii ORNs do to help the host prompted me to look at various animals and the immune system’s response to ORNs.
Arun Adhar had developed a test to determine whether feeding L. caseii ORNs could protect shrimp from a lethal virus that was wiping out ponds of commercial shrimp around the world. Yes, he found it reduced mortality by 80 percent. Other tests showed that feeding the ORNs gave significant protection against shipping fever in cattle, bacterial infections in fish and recently, PEDv infections in piglets.
What are these ORNs and why have the immune systems of so many different animals developed a broad conserved protective response to their appearance?
Recent research indicates that these particular ORNs control the growth of fungi and bacteria by controlling the expression of growth genes in their genomes. After ORN release, the bacteria immediately enter accelerated growth without first spending hours in a mysterious “lag,” discovered back in the 1890s and still not understood even today. During the lag, which can last all day, bacteria appear to be doing nothing. Its function is unknown, but at least now we know what controls it—the ORNs.
Over eons of the co-evolutionary cold war waged between beast, man and the microbe, the immune system has learned: 1) not to waste precious time determining whether the invader is friend or foe or even whether it is fungi, bacteria or toxins; 2) to initiate a response that meets all comers; and 3) to spread the response mechanism across all types of animals, not just humans.
In the twenty-first century we now face a new set of attackers: the zoonotic viruses that jump from wild animals to mankind. We need an immediate treatment; we can’t wait out the several years it takes to develop a vaccine. What I do know is that ORNs are naturally-derived over centuries of co-evolution and are safe and effective but I don’t understand the steps in stopping an infection. The details are extremely important in understanding how the immune system works.
- caseii is a dietary ingredient found abundantly in non-pasteurized milk and fermented dairy products. Other species of ORN-releasing lactobacilli occur broadly in fruits and vegetables and have been consumed by man and beast forever. But today’s diets contain pasteurized milk and too many sterile meals and snacks of processed foods. By the way, commercial yogurts have far too few and probiotics yield practically none since they are grown and processed in a way that washes the ORNs down the drain. So, the dietary contribution of released ORNs for most people is low.
In animal husbandry, processed feeds are not adequate sources of ORNs, and we know that most farm animals are highly stressed. Using L. caseii, I developed a product that can be fed to animals to “restore an immune system compromised by stress.”
But LactORNs© is only a start in applying this new paradigm to protect animals against infections. Over the last few years, I assiduously apprised the agency of our results and their significance.
Searching for new antibiotics is not the solution. During the eons of microbial cold wars, nature has taught bacteria and fungi how to construct a molecule that would control the limits of encroaching microbes. Each synthesizes an antibiotic to stop a neighbor from gaining the upper hand. Antibiotics restrict growth to a certain level that allows mixtures of microbes to live peacefully with each other. But the antibiotic paradigm is not one for us; we have too many niches where their dormant forms can hide out.
Microbes have theirs and we need ours. The dietary ORNs released by harmless bacteria appear to stimulate our defenses against all kinds of harmful microbes. So far, our research has demonstrated that feeding LactORNs©, naturally released by naturally-grown L. caseii prevents new viruses from killing shrimp and piglets. Our human immune studies indicate that they will do the same for humans.
Our success to this point isn’t enough. Professor Fred Kummerow, my mentor who discovered the harm that dietary trans fats can do, is now one hundred years old and still working to gain full acceptance of a discovery he made sixty years ago. The FDA needs to start work to understand the ORN paradigm and put their shoulders behind it.
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Fall 2014