Sunday November 1, 2009
Gut gives nose heads up
By LEE TSE LING
Friendly bacteria might help protect you against flu, studies say.
A DAILY dose of live bacteria may be useful in fighting off flu infections in the upper respiratory tract. This is the conclusion of various studies, including two conducted on old and young mice at the Yakult Central Institute for Microbiological Research (YCIMR) in Tokyo, Japan.
The results of these were published in Clinical and Diagnostic Laboratory Immunology in 2002 and 2004 respectively. One of the co-authors, Professor of functional food sciences Hisako Yasui from Shinsu University, was invited to discuss these results and the topic of probiotics and immunity with our group of visiting Malaysian and American journalists on Oct 2 as part of Yakult’s 2009 journalist tour in Japan.
Prof Hisako Yasui ... Lactobacillus casei strain Shirota may be useful in preventing viral respiratory tract infections for elderly individuals with low immune function and infants with immature immune systems. Mice with flu
In the first study, 15-month-old mice (which is considered old, for a mouse) were fed Lactobacillus casei strain Shirota (LcS) daily for four months, then infected with a laboratory influenza A(H1N1) strain.
In the second, two-day-old mice (which is considered very young, for any mammal) were fed LcS at various intervals for three weeks, then infected with the same A(H1N1) strain.
In both studies, the effect of the LcS diet in activating virus-attacking cells and communication between immune system cells, and the amount of flu virus in nasal washings were measured.
Like humans, old mice have low immune function and young mice have immature immune systems. As a result, both are high-risk groups for influenza infection and complications. Previous studies, performed in vitro (“outside the body”), had indicated LcS was capable of stimulating immunity. The common objective of Prof Yasui’s studies was to see if feeding LcS to a live organism would protect it from flu virus infection in these high-risk populations.
Additionally, the researchers were interested to see where the effects would be detected – all over the body, or, hopefully, targeted in the upper respiratory tract where the viral load was high?
LcS 101
The human gut is home to many billions of live bacteria of several hundred species. It’s a thriving melting pot of microbes, in which lactic acid bacteria of the genus Lactobacillus are but one group of residents.
Dr Masanobu Nanno ... Some part of the Lactobacillus casei strain Shirota may be incorporated into the body in the Peyer’s Patches (groups of lymph nodes) in the small intestine. LcS, Lactobacillus casei strain Shirota, is distinguished by the fact that it is able to survive the harsh acid bath of the stomach in order to reach the intestines alive to do its probiotic job in the intestines. The strain was named for the Kyoto University medical doctor and professor who first isolated it from the human gut, Dr Minoru Shirota (1899-1982).
Nowadays, we associate the Japanese way of life with balance, vitality, and longevity. But in the early years of Dr Shirota’s career, this was not so. Embroiled in a series of wars and ravaged by the 1923 Great Kanto Earthquake, Japan was a beleaguered nation in which healthcare was costly and many lost their lives to preventable gut infections like food poisoning, dysentery, cholera, and typhoid.
Based on his studies on intestinal bacteria and their effect on human health, Dr. Shirota was convinced a healthy population of gut bacteria would go a long way in preventing such diseases. The easiest way to achieve that, he decided, was to introduce good bacteria to the gut on a daily basis by drinking them. And so began development of fermented milk drinks containing live LcS, which consumers have been downing since its introduction in 1935.
Dr Shirota’s philosophy of preventive medicine was a significant departure from the then-prevailing theory of therapeutic medicine. It formed the core of his life’s work, and lives on today, enshrined as Shirota-ism, the governing philosophy of the public-listed, multinational Yakult Honsha Co Ltd.
So much for history. Now back to the mice.
Important results
In Prof Yasui’s studies, the LcS diet was associated with:
·A lower viral load. In both studies, the amount of flu virus in the nasal washings from the upper respiratory tract of mice fed LcS was significantly lower compared to mice that weren’t fed LcS.
·Fewer deaths, milder symptoms. In the young mice study, the survival rate after the flu infection travelled to the lower respiratory tract was significantly higher in the mice fed LcS. Their accumulated symptom rate was also lower.
·More virus-targeting cell activity. In both studies, natural killer (NK) cell activity in the lung cells of LcS-fed mice was significantly higher. That means the NK cells in the LcS-fed mice were actively targeting and attacking more virus-infected cells.
·More immune system communication. In the old mice study, production of antiviral and macrophage-activating chemicals (macrophages gobble up viruses and other invading bugs) in the upper respiratory tract lymphoid tissues was significantly higher in the LcS fed mice.
In the young mice study, production of a chemical that activates NK cells in the lower respiratory tract lymphoid tissues was higher in the LcS fed mice.
LcS may therefore be useful in preventing respiratory tract infections for elderly people, neonates, and infants, Prof Yasui concludes. But how does something in your gut protect you from flu viruses up your nose? E.g. how does LcS within the enclosed gut reach immune system cells, like NK cells, circulating in the body?
Tail to nose eating
“We don’t have a direct answer at this moment,” acknowledges YCIMR senior researcher Dr Masanobu Nanno. “But in mouse experiments, we know LcS can be detected in the Peyer’s Patches. So one possibility is that some part of the LcS is incorporated into the body there.”
Dr Nanno also notes only small amounts of LcS have been detected in the Peyer’s Patch pathway, indicating other pathways are involved.
Peyer’s Patches consist of groups of lymph nodes in the small intestine. The current hypothesis is that special cells in the patches “sample” the contents of the small intestine and “present” them to the immune system, thus stimulating it. These cells can do so because they are located on the surface of the gut lining. On one side, they’re exposed to gut contents. On the other, to the inner workings of the body.
You can think about it this way: What’s goes into the gut comes from outside the body. As such, it may contain harmful germs. To prepare itself for attacks from germs it swallows, the body’s immune system has special stations in the gut – the Peyer’s Patches – where it can monitor what’s sloshing around.
When it spots a suspicious germ, it takes a molecular “snapshot” of it, and tells the rest of the immune system to be on alert. In the case of a flu infection, this alert eventually circulates to the local immune system in the respiratory tract, and inspires heightened activity there. (See the accompanying graphic, Immune booster, to see how Prof Yasui’s group thinks this happens.)
Some lactic acid bacteria like LcS and many pathogenic (disease-causing) germs have this ability to put the body on alert, Prof Yasui points out. It is, after all, the natural response of a working immune system to protect the body against harmful invaders. What sets LcS apart from a pathogenic germ, and makes it useful as a probiotic, is the combination of its ability to put the body on alert and its harmlessness.
You might be wondering why LcS can prime a response against A(H1N1) when it doesn’t remotely resemble A(H1N1). That’s because the immune reaction observed in Prof Yasui’s studies is innate immunity, not acquired immunity. In other words, it is a general response versus a specific response.
The human immune system consists of acquired immunity and innate immunity. Acquired immunity is like a special investigative force that studies its suspect thoroughly before launching a well-planned assault e.g. with antibodies and “educated” helper and killer T-cells. Acquired immunity is what protects you after you’ve been vaccinated.
Innate immunity is your first line of defence against harmful germs. It’s like a standing force of police officers that protects citizens against general crime. More active cops (or cells) means more criminals (or germs) caught.
DON’T try this at home
Interestingly, in a previous study, Prof Yasui found that LcS triggers a stronger immune response when squirted up the noses of flu-infected mice.
“If it is administered intra-nasally, it is very close to the respiratory system, which is the focal point of infection. When we administer it intra-orally, there is a ‘distance’ between the gut and respiratory tract,” she says.
Note: Yakult categorically does not recommend intra-nasal administration of any of its LcS products.
DO try this at home
So daily doses of LcS can pump up immunity in mice. What about in humans?
In a 2006 study published in Vaccine, the administration of lactobacilli and bifidobacteria significantly reduced the duration and severity (but not incidence) of common cold episodes in 479 healthy adults, who were supplemented with vitamins and minerals and assessed over two winter/spring periods. (The common cold is caused by a variety of viruses.)
In another 2009 study published in Vaccine, daily consumption of a probiotic drink containing a strain of Lactobacillus casei and yoghurt ferments significantly improved antibody production in response to influenza vaccination in 308 elderly volunteers.
Based on these, and many others, it seems the regular consumption of probiotics does benefit the immune system, and in a multitude of ways, although the exact mechanics of this effect aren’t known.
Do all good bacteria boost immunity? Can some boost acquired immunity, as seems to be the case in the 2009 Vaccine paper? It’s hard to soundly say without further research, especially since results from any study represent only measured and/or measurable effect, as opposed to actual effect.
What can be said though, while we wait for the men in white coats to give us the specifics, is you’d do pretty well to keep bad bugs at bay, even ones as far away from your tummy as your honker, by eating some good ones every day.
How much do you need? The mice in Prof Yasui’s studies were fed a 0.05% diet of LcS. To achieve the equivalent in a human, she suggests swallowing about 30 billion live LcS bacteria a day.
References:
1. Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. De Vrese M et al, Vaccine 2006 Nov 10; 24(44-46):6670-4
2. A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Boge T et al, Vaccine 2009 Sept 18; 27(41):5677-84
3. Augmentation of cellular immunity and reduction of influenza virus titer in aged mice fed Lactobacillus casei strain Shirota. T. Hori et al, Clin Diagn Lab Immunol 2002; 9: 105-108
4. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota. H. Yasui et al, Clin. Diagn Lab Immunol 2004; 11: 675-679
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