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Paper
Summary: Lactobacillus
plantarum strain
maintains
growth of infant mice
during chronic undernutrition
Summary
Growth in mammals experiencing extended undernutrition is stunted as a result of growth hormone resistance and, subsequently, inhibition of the somatotropic axis. The role of the microbiota in weight loss as a result of temporary malnutrition has been studied, however the role of the gut microbiota on early growth processes during chronic undernutrition is not known (Hizli et al., 2007). In this study, the researchers aimed to characterize the role of the gut microbiota in somatotropic axis function and postnatal growth. They were first able to show that germ-free (GF) mice exhibit growth deficiencies when fed normally, compared to WT. Next, they determined that GF mice experience decreased somatotrophic axis activity and determined that microbiota aid growth by promoting IGF-1 activity and production within the somatotropic axis. Lactobacillus plantarum was identified in Drosophila as a growth-promoting bacterial strain. The researchers determined that mice monocolonized with one of two Lactobacillus plantarum experienced increased growth during malnutrition compared to GF mice. Additionally, one of these strains was shown to increase somatotropic axis activity during malnutrition.
This study characterized the role the microbiota play in promoting postnatal growth and maintenance of somatotropic axis activity. The microbiota is shown to be necessary for normal postnatal growth under normal and under-nutrition conditions. The microbiota is shown to aid growth by increasing activity of IGF-1 and bacteria Lactobacillus plantarum was shown to be specifically beneficial for alleviating growth defects related to malnutrition. They hope that supplementation of the gut microbiota could help with human growth defects related to malnutrition.
My Opinion
This paper was thorough, easy to understand, and provided clear and strong evidence to back up their claims. Overall, I was convinced by their data and conclusions. I felt that their ultimate focus on one bacterial strain was good for simplicity, however it may be a good idea in the future to characterize the growth-promoting capabilities of other strains in the interest of being thorough. I'd be interested to know if there are combinations of bacterial strains that can be implanted together that may increase the growth response even more. I think the paper could benefit from moving the final four panels of Figure 4 earlier in the paper. Characterizing the impact of IGF-1 inhibition supplements their claims made from earlier figures much better. Overall, this is a good paper that clearly states relevant information, results, and necessary conclusions.
Figure 1: The initial question was whether the microbiota has an effect on growth in mice. WT mice and germ-free mice were fed a standard diet. Panels A-D show that GF mice exhibit stunted growth under normal feeding conditions with A and B specifically addressing weight gain and panels C and D addressing length of the body. Panels E and F show that GF mice exhibit stunted skeletal growth based on decrease in femur size cross all dimensions. Data from this figure indicate that the microbiota are necessary for normal body size and bone growth.
Figure 2: It is known that the somatotropic axis drives systemic growth, and the researchers wanted to determine the effect of the microbiota on this hormonal pathway. In panels A-C, relative amounts of key hormones in this axis were found circulating in blood from GF and WT mice. Significant differences in abundance of IGF-1 and IGFBP-3 were found between GF and WT. Relative expression of genes coding for IGF-1 and IGFBP-3 were significantly decreased in GF mice based on transcript abundance in liver cells. Phosphorylation of AKT, a good indicator of IGF-1 receptor signalling activity, was found to be decreased in GF mice using a western blot with antibody stains for phosphorylated and unphosphorylated AKT. The data in this figure indicate the microbiota are necessary for normal somatotropic axis activity.
Figure 3: The bacteria Lactobacillus plantarum identified as a growth-promoting bacteria and the researchers wanted to determine if supplementing mice with it would alleviate growth defects related to malnutrition. Ultimately, the data show that GF mice have significant growth defects under both normal and depleted diet conditions. Supplementation with one strain of Lactobacillus plantarum alleviates the effect seen in GF mice during malnutrition and maintains postnatal growth of mice.
Figure 4: After determining that Lactobacillus plantarum maintains postnatal growth during malnutrition, the researchers wanted to determine if this strain was acting by maintenance of the somatotropic axis. Abundance of circulating hormones in the blood of WT mice, mice colonized with Lactobacillus plantarum, and GF mice. One strain of Lactobacillus plantarum was shown to bring IGF-1 levels near to levels seen in WT. It was previously shown that the microbiota likely acts on growth through the activity of IGF-1, so this matches this important claim. Panels D-G show the effects of inhibiting IGF-1 with PPP on weight gain, body length, and femur length under normal and depleted dietary conditions. Under normal diet conditions, inhibition of IGF-1 significantly decreased all three measurements. Under depleted dietary conditions, no significant difference is seen in weight gain or body length gain. These results are a supplementation to the importance of IGF-1 activity on systemic growth.
Citations:
Hizli,
S., Abaci A., Büyükgebiz B., Büyükgebiz A., (2007) Pediatr.
Endocrinol. Rev. 4, 186–195.