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Paper Review: "Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition" by Schwarzer et al.

Overall Summary

• Postnatal growth driven by somatotropic axis
• Growth hormone (GH) instructs liver and other tissues to produce insulin-like growth factor-1 (IGF-1)  and IGF-1 binding protein 3 (IGFBP-3) which triggers tissue growth
  
• Organisms gain GH resistance with chronic undernutrition
  
• Wild-type (WT) mice were found to be larger than germ-free (GF) mice when both were fed a regular diet
• Similar adiposity and leptin levels
  
• Wild-type had larger organs and longer spines
• Similar bone mineral densities
  
• While GH levels were similar in both, IGF-1 and IGFBP-3 concentrations were lower in GF mice
  
• Igf1 and Igfbp3 expression in the liver were also reduced in GF mice
• When recombinant IGF-1 was introduced to both WT and GF mice, growth was similar to WT in both
  
• When an IGF-1 inhibitor was introduced to both, growth was similar to GF in both
  
• When both mice types were introduced to a restricted diet, GF mice growth stopped while WT animals continued to grow
• Attempted to find bacterial strain to explain growth changes
• Found two Lactobacillus platnarum strains
• Lp-WJL and Lp-NIZO2877
  
• GF mice were colonized with the two strains
• Both gained more weight compared to GF, with Lp-WJL gaining more
• Both maintain somatotropic axis activity unlike GF
• Higher IGF-1 and IGFBP-3 levels

  Opinion

    I found this paper fairly compelling, as a consistent story was told and it was easy to follow. The required background information was quickly and concisely explained which allowed the authors more space to analyze and discuss their results. Most questions I would have had were explained through further experiments, especially where they introduced IGF-1 and the IGF-1 inhibitor to both mice types. I also liked that they looked at both concentrations of IGF-1 and IGFBP-1 as well as their genes, which provided a compelling a consistent argument. The other thing that I would have been interested in was the comparisons between organ growth, which was in the supplemental information.

    However, I did have a few issues with the paper. First, they discuss how a separate paper found that bone mineral density was different in the two mice types from a different genetic background. The paper seemed to glance by this and focus on postnatal tissue growth, but then later on they continued to measure skeletal growth throughout the paper. The other issue I had, which was more minor, was that the information for figure 4 was introduced before figure 3 and somewhat sporadically. I just found this a little hard to follow as they had not yet discussed the bacterial strains which were an important pat of figure 4. Also, for figure 4, they introduced DMSO without any explanation of what it was, which made it difficult to understand.

Figure Summaries

    Figure 1: Mouse juvenile growth maintained by the microbiota. WT mice were both larger and longer than GF mice after weaning. Growth for both was approximately the same up until weaning. The femurs of WT mice were larger than GF mice.

    Figure 2: Somatotropic axis activity, which facilitates juvenile growth, was maintained by the microbiota. GH, IFG-1, and IGFBP-3 levels were all higher in WT mice. Igf1 and Igfbp3 expression levels were also higher in WT mice. Lastly, AKT levels were higher in WT mice.

    Figure 3: L. plantarum and the microbiota maintain juvenile mice growth for normal and restricted diets. The weights of all mice were smaller when on a restricted diet versus a normal diet. WT mice were the largest and the longest, closely followed by GF mice monocolonized with Lp-WJL, with GF mice monocolnized with Lp-NIZO2877 the next largest and longest, and GF the smallest and shortest.

    Figure 4: For mice with restricted diets, L. plantarum and the microbiota were able to maintain somatotropic axis activity. IGF-1 and IGFBP-3 levels were highest in WT mice at 56 days, followed by Lp-WJL and Lp-NIZO2877, GF mice with the lowest levels. GH levels were similar amongst all four. Introducing an IGF-1 inhibitor resulted in lower mice weight gain, length gain, and femur length.

Assignments:

Assignment #1: 4D Genome