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plantarum strain maintains growth
of infant mice during chronic undernutrition"
This paper (Schwarzer et al.
2016) explores the effects of gut microbiota on nutrition-dependent
growth of infant mice. Specifically, the team investigates what impacts
the presence and absence of L.
plantarum strains have in promoting the growth of juvenile
mice. They deduce that the bacterium interacts with growth-related
hormones in the somatropic axis to allow weight and length growth in
germ-free mice comparable to that of wild type mice in both normal
breeding diets and nutrient depleted diets. They connect these
physiological growth responses to changes in Growth Hormone (GH) and
Insulin-Like Growth Factor-1 (IGF-1), and make the claim that the
microbiota directly promotes growth by facilitating production and
activity of these biological products.
While this paper
investigates an interesting phenomenon of the microbiota's role in
growth, it takes what starts as a discovery science paper and develops
it into a validation science paper, by the use of the researchers'
previously known bacterial strain, L.
plantarum, which they had seen to function similarly in
Drosphila. By doing so, the investigators limit their findings
to validation, instead of looking for any other bacteria that might also
impact this response. They didn't look into what bacterial populations
were present in the mouse gut naturally, or investigate if other
bacteria also caused similar GH and IGF-1 responses. I feel as though
the investigators were not doing their responsibility as scientists to
take an honest look at a system and explore seemingly unpredicted data,
and instead chose to focus only on the data that would validate the idea
that they had before beginning investigation. They also conclude that
microbial interventions could buffer the adverse effects of
undernutrition; however, the microbial interventions would just be
towards a typical microbiome (WT mice) instead of no microbiome (GF), as
the addition of an exclusively L. plantarum microbiome didn't improve
from the WT condition experiencing undernutrition. The real best way to
combat undernutrition is with increased nutrition.
researchers begin by asking what effect the presence or absence of
normal gut microbiota has on juvenile mouse growth post-weaning.
They fed both wild type (WT) and germ free (GF) mice on a standard
breeding diet, and measured their subsequent weight gain,
longitudinal growth, and skeletal growth. They found that GF mice
had significantly lower weights and smaller body lengths (including
skeletal growth) than their WT counterparts, especially after
then looked at what effect the presence or absence of gut microbiota
had on the somatotropic axis. The researchers measured the
circulating levels of growth hormone (GH), insulin-like growth
factor-1 (IGF-1), and its binding protein (IGFBP-3), all major
factors in regulating growth. They found that for both GF and WT
mice, the GH levels peak around birth and gradually decline.
However, IGF-1 and IGFBP-3 are present in significantly higher
amounts in the sera of WT mice than in that of GF mice. They also
saw that expression levels of the Igf1 and igfbp3 genes in the liver
drop in the GF mice when their products peak in the WT mice.
Phosphorylation of AKT in the WT mice showed that their IGF-1
receptors had signaling activity. Overall, they show that the
somatotropic axis is more active in mice with gut microbiota.
next wanted to see if recovery of typical growth could be achieved
via introduction of L. plantarum
into the GF mice. A subset of GF mice were born to parents
(and therefore naturally colonized) with one of two strains of L.
plantarum, one (LpWJL) which they had previously identified
as a potent growth promoter, and the other (LpNIZO2877) which had a
less profound effect in previous research. They performed the same
analysis as in figure 1, and found that the LpWJL strain maintained
WT-like growth in the mice, while the LpNIZO2877 also led to a
recovery of growth, but not as much as LpWJL.
Then they took all four mice conditions and performed a similar
experiment, except with a nutritionally depleted diet. While all
mice exhibited less growth than in the breeding diet condition, they
saw the same response of the mice to the Lp strains as before, the
differential recovery of GF mice towards WT growth responses.
researchers then looked at what the growth-related hormone and
protien levels looked like in these four conditions of mice with
different microbial compositions in undernutritional diets. They
used the same analysis of sera as in Figure 2. They found that LpWJL
mice tended to have the same relative concentrations of these
factors as WT mice, while LpNIZO2877 trended with GF mice. They
explain the data as demonstrating the reduced activity of the
somatotropic axis in GF mice and mice with LpNIZO2887.
They next tried to simulate the lack of IGF-1 activity (as in the GF
mice condition) in WT mice to see what their weight gain and body
length responses would be, thereby directly linking that growth
factor with mouse growth. They injected WT mice with an IGF-1R
(IGF-1 receptor) inhibitor, picropodophyllin (PPP) and measured
weight gain and length as in figure 1, and relative femur length.
The control injection is DMSO. They found that the PPP led to
lowered weight gain and body length gain in the breeding diet, and
shorter femur length in both the breeding and depleted diets.
Therefore, they conclude that the IGF-1 must bind and be active (as
in the LpWJL and full microbiota conditions) in order for the mice
to grow as normal.
M et al. 2016.
Lactobacillus plantarum strain maintains growth of infant mice
during chronic undernutrition. Science, vol 351 issue 6275
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