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Assignment 2

Effect of Lactobacillis plantarum strain on growth of infant mice during chronic undernutrition"

Summary: A recent study conducted by Schwarzer et al. investigated how microbiota composition affects systemic growth in mice. Postnatal growth in mice is largely regulated by the somatotropic axis. The release of growth hormone (GH) from this axis initiates the release of Insulin Growth Factor-1, which allows for organ and systemic growth from the liver, but mice become resistant to GH in states of undernutrition.

With this in mind, their starting experiment analyzed how germ-free mice post-weaning have lower weights and lengths than their wild-type counterparts though both cohorts ate similar amounts of food. This led them to hypothesize that gut microbiota were key to optimal weight gain and somatic tissue growth around weaning. They also analyzed the effects of monocolonization of two Lactobacillis plantarum strains, LpWJL and LpNIZO2887, in germ free mice on their growth and length and saw recovered weight and body length both when the mice were on either a depleted diet or a breeding diet. The positive effects of LpWJL were more pronounced than LpNIZO2887, and LpWJL colonization in undernourished mice was even able to bring GH and IGF-1levels to the same level seen in wild-type mice.

This paper demonstrates that the growth hormone-resistance phenotype seen in undernourished young germ-free mice may be changed to a wild-type phenotype with the introduction of Lactobacillis plantarum, a wild-type microbe. Since this microbe changes the liver's sensitivity to GH, the mice are able to process IGF-1 which allows them to grow in a way more similar to the wild-type mice under depleted diet conditions. If this bacteria or another with similar effects impacts humans in a similar way, this paper presents some unique insights to how we can improve undernutrition interventions.

This paper is well-written and presents and convincing argument about the potential role select microbes could have in combating the negative side effects of malnutrition. Their figures were well thought out and clear, and I appreciated the author's insights and interpretation of the data. I am excited about the implications that this paper may have on global health if similar phenomena are seen in humans.

The following figures come from "Lactobacillis plantarum strain maintains growth of infant mice during chronic undernutrition" by Schwarzer et al., 2016.

Figure 1

Figure 1 shows the differential weights and body lengths of germ-free and wild-type mice post-weaning. Though the germ-free and wild-type mice had similar eating patterns, the wild-type mice had significantly higher weights, growth rates, and body lengths. Additionally, the differences in weights did not come from differential adipose tissue amounts, but from differential organ and systemic growth between the two groups. Since germ-free mice do not have the microbes necessary to facilitate IGF-1 production and activity, they do not grow and develop at the same rates of wild-type mice. This is evidenced in 1E and F, which show the physical differences between the femurs of wild-type and germ-free mice.

Figure 2

Figure 2 provides evidence suggesting that IGF-1 in germ-free mice is not produced at the same levels as in wild-type mice even though both groups produce comparable amounts of GH. This is because the germ-free mice are resistant to GH and are unable to produce proper amounts of IGF-1 for optimal development. Furthermore, there was reduced levels of the IGF-1 receptor, IGFBP-3, and expression of Igf1 and Igfbp3 in the liver.

Figure 3

Figure 3 shows that, while the introduction to germ-free mice of both of the Lactobacillis plantarum strains affects the weight and body length of mice positively, the introduction of the strain LpWJL fully or almost fully recovers the wild type phenotypes no matter if the mice are put in depleted or breeding diets. As seen in both 3A and 3B, germ-free mice that are exposed to LpWJL gain weight and body length in ways similar to wild-type mice.

Figure 4

Figures 4A-D show that germ-free mice under starving conditions that are given LpWJL have GH and IGF-1 levels similar to wild-type mice. 4A provides further support that microbiota provide the means to process GH and make IGF-1 correctly because, with the introduction of LpWJL, GH levels return to that of wild-type mice. 4D and E show that PPP, an inhibitor of the IGF

Citation

Schwarzer, M., Makki, K., Storelli, G., Machuca-Gayet, I., Srutkova, D., Hermanova, P., Martino, M.E., Balmand, S., Hudcovic, T., Heddi, A., et al. (2016). Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science 351, 854–857.

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