Legend has it that while the Mongols were invading a certain country, a thirsty messenger, riding across a desert, requested some villagers to refill his water pouch. The villagers, angry at Ghengis Khan’s assault and the plight that followed, filled the water pouch with milk instead.

While crossing the desert, the soldier discovered a sour, watery, custard like substance in his pouch instead of water. But desperate to quench his thirst he drank it. To his surprise it was not only an excellent substitute for water but also energizing! After this incident, sour milk became an indispensable part of Ghengis Khan’s army rations.

This story is by no means the earliest mention of the advantages of probiotics. Texts across the world, from the Old Testament to the Vedas, mention the medicinal properties of probiotics.

Probiotics such as wine, yogurt, curd, yakult and many other fermented products have been a part of our diet for hundreds of years. Their advantages in digestive health are thought to be evident in humans as well as in animals.

Luis Pasteur was one of the earliest to note the presence of lactic acid producing microbes in the fermented milk products. Since then numerous other scientists, including the Nobel laureate Elie Metchnikoff —who coined the term “probiotic"—have confidently assigned the positive effects of probiotic food and drink to the microbes present in them.

In 2017, one would be tempted to dismiss a clinical trial of a probiotic as stale news. Quite the contrary. A study published in Nature is making waves for its findings. Conducted in Odisha, this study is one of the very few to clearly demonstrate a significant health advantage of a probiotic.

But first, a little background.

The term these days specifically refers to the microbes whose consumption confers a health advantage. Unfortunately, scientific studies cannot support this assumption adequately. Probiotic foods can have positive effects on one’s health. But whether these effects are due to the commonly acidic nature of probiotic food or the microbes involved, or something else altogether, remains unclear.

It has, in fact, proven surprisingly difficult to clearly demonstrate the definite role of these microbes and, more importantly, the underlying mechanism. A major hurdle in the process is the diversity of the gut environment.

The average adult human will have 400 varieties of microbes in his gut, and up to approximately 10 to the power 14 individual microbes in total. The composition varies across individuals as well as across different regions. Dietary habits, age and infections experienced during the life are also factors that affect the composition of gut microbes. The newborn foetus also carries the microbes acquired from its mother during development, and continues to build up its repertoire after birth.

The “microbiome", or the collection of all the microbes, of any individual is thus a complex community and its dynamics are as abstruse, if not more, as a modern economy.

This microbiome also functions as a defence against the disease-causing germs that enter the gut through the food or water we take in. This defence uses a two-pronged approach to fight invaders.

First, it tightly holds itself to the lining of the gut, occupying most of the available space. Invading microbes are thus left in the gut without an anchor and can be washed off by the rhythmic flushing, called peristalsis, inside the gut. The second strategy involves secretion of chemicals which are harmful specifically to non-residential microbes.

These defence mechanisms put forth by the resident microbes can be weakened under many circumstances. One is the use of antibiotics, which kills the resident microbiome along with the disease-causing germs. Another is excessive hygiene, especially in the case of newborn babies, where the crucial process of acquisition of the microbiome is ongoing.

Stress is another known threat to our microbiome, as it results in hormonal secretions that reduce the mucus content in the gut. Mucus is needed to hold the microbes to the walls of the gut and its absence results in an ineffective cover formation. Once the defence is compromised, infectious microbes can find their way in our body.

In other words, we could actually help our own gut microbes to fight the infections by restricting the use of antibiotics and leading a stress-free life.

So what role do probiotic supplements play?

Initially, it was thought that the microbes in probiotic foods, such as Lactobacillus, Streptococcus or Bifidobacterium, are the key members of the resident gut flora. Eating probiotic foods was assumed to restore the key microbial components of the gut. Till now, however, there has been no scientific evidence to back this.

Trials with the candidate microbes do not show a conclusive improvement in humans with digestive disorders. Even combined formulations of multiple microbes are not consistently effective. In case of animal feeds, where probiotics are routinely used as food supplements, the specific role of these microbes is far from evident.

The Nature study is a significant breakthrough on this background. Two attributes set it apart from its predecessors. One is the large sample size—nearly five thousand infants. The second is that it was a randomized double-blind design—the gold standard of clinical trials.

An experiment is a double-blind study when neither the subject nor the experimenter know whether they are being given the treatment or the placebo. Their allotment to either the test or the control group is random as well. A collaboration between multiple institutes spread over US and India, this trial tested the effect of probiotics on sepsis in infants.

Sepsis is primarily our body’s immune response to an infection and it can result in fever, cough, increased heart rate, compromised circulation and even kidney dysfunction. Sepsis-associated mortality is particularly high in infants. Every year, it claims the lives of more than half a million newborns worldwide, a majority of them in developing countries.

The subjects of the study were 4,556 infants from a region of Odisha with high incidence of sepsis. Half of them were given Lactobacillus along with a specific sugar solution which promotes the growth and colonization of the probiotic. During the 60-day monitoring period, it was found that the treatment reduced the incidence of sepsis and sepsis-related deaths by nearly 50%.

More surprisingly, the treatment also reduced the occurrence of other secondary complications, such as diarrhoea, respiratory tract infections, ear infections and abscess. The authors of the study suspect that the treatment boosts the general immune response of the infants which, results in the lower rates of infections observed.

Finding out the exact mechanism behind these exciting observations is probably going to keep scientists busy for years to come. Despite a lack of clear understanding of the underlying mechanism, this study is a big step forward for probiotics. Even if the same probiotic might not be effective in treating sepsis all over the world, it will definitely accelerate the search of a suitable substitute. Given the scale of the sepsis menace, even a modest improvement over the current scenario will be a significant leap towards providing relief to the affected.

Furthermore, the study strongly suggests that non-customized probiotic treatments can be most effective in the early life of humans. With increasing age, individual differences between microbiomes are bound to increase, leading to a concomitant decrease in effectiveness of any general probiotic formulation.

And, last but not least, probiotic supplements can also be strong candidates to curb the use of antibiotics and slow down the spread of antibiotic resistance.

Shraddha Karve is postdoctoral scientist at University of Zurich.

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