Invisible allies for healthy juvenile growth
Maybe you remember it from your childhood. There was a doorframe in your parents' house, marked by a ladder of small horizontal lines, with dates and your name written next to each line: the more recent the date, the higher the position of the line. This simple growth chart recorded your height at a given age, and how much you grew from the last time. And probably you took it completely for granted that as the time passed, each line was drawn above the last, never wondering how this all works.
Nowadays we know that the gain in body size during the infant growth period is a result of the interactions between nutrition and the organism's hormonal cues. In mammals, post-natal growth is controlled by the Growth Hormone, which instructs the tissues to produce Insulin-like Growth Factor-1 (IGF-1), which then promotes organ and systemic growth. When food is scarce for a long time or the diet doesn't contain enough nutrients (situations defined as chronic undernutrition), juveniles stop growing and in the long term become small and thin (1). If we return to our doorframe growth chart parallel, it would mean that there would be more dates at the same line. In certain parts of the world, such as Africa and India, childhood undernutrition is a major health threat, especially for the long term consequences which besides stunting include also neurocognitive deficits. However, it seems that it is not only the amount and quality of food that matters for the growth. Recently, a consistent body of research (2) suggested that the bacteria in our intestines, the so called gut microbiota (read also the Break: Cold adaptation: gut bacteria can make the difference), might play an important role. Therefore, we wanted to find answer to the question: What is the contribution of this gut microbiota to postnatal growth during feeding on rich diet and during chronic undernutrition?
To explore this we studied two groups of mice: conventional mice harboring a normal intestinal microbiota and germ-free mice, which are devoid of any detectable living bacteria. Juvenile male mice received rich diet, which had all the necessary nutrients in sufficient amounts, and we followed their growth until young adulthood. Conventional mice showed better growth rate compared to their germ-free counterparts and such difference was not caused by bigger fat stores but, instead, by overall organ and bone growth. In accordance with this physical difference, microbiota also increased the titers of growth promoting IGF-1 in the sera of conventional mice.
Having established the crucial role of microbiota for optimal growth in nutrient rich conditions, we wanted to know if it plays the same role in chronic undernutrition. To test this, we designed a diet, which was low in proteins and fats, but provided the mice with the same amount of calories thanks to addition of carbohydrates. When the juvenile male mice received this depleted diet, we observed that the germ-free mice failed to grow - they were completely stunted. On the other hand, their conventional counterparts harboring the bacteria continued to grow, although the growth rate was slower than that of the conventional mice fed the nutritionally rich diet.
Concerning the host growth and bacteria colonization, our lab has previously shown that certain specific bacteria from the species Lactobacillus (L.) plantarum are able to promote growth of the Drosophila larvae upon feeding on diet low in proteins (3). L. plantarum belongs to the lactic acid-producing bacteria and these are nomadic bacteria that can be found in different habitats, such as soil and fermented foods, but also in the intestinal tracts of both invertebrates and vertebrates, including mice and humans. We were therefore wondering: Will the single bacterium which promotes growth in Drosophila model, be able to promote the growth of the stunted germ-free mice? And to what extent? To this end we provided the germ-free mice with the growth-promoting strain L. plantarumWJL and submitted them to the depleted diet. We observed that the mono-bacterium-associated mice grew as well as the conventional mice on the depleted diet and that this one L. plantarum strain increased the levels of growth promoting IGF-1 in sera to the same extent as we observed in the conventional mice.
Thus our work established that microbiota is necessary and that specific L. plantarum bacterial strain is sufficient to boost juvenile growth rate. Based on these findings we envision that, together with supportive nutrition strategies, microbial interventions using specific bacterial strains may represent a novel and useful strategy to limit the adverse effects of chronic undernutrition on post-natal growth - a threat that still affects more than 160 million of children below 5-years of age in low- and middle-income countries.
Schwarzer M, Makki K, Storelli G et al. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 2016;351(6275):854-857. doi:10.1126/science.aad8588.
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