The long held notion
of ‘junk DNA’ has been found to be incorrect (ENCODE project), similarly,
characterizing the gut microbiota as bystanders in the intestinal tract is now being
widely challenged (Osborn O, Olefsky JM (2012), Nature Med 18(3):363-374).
A recent paper in
Proceedings of National Academy of Sciences (PNAS) adds muscle to the fact that
a single species of bacteria (Akkermansia
muciniphila) can modulate diet induced obesity in mice. A. muciniphila is a
Gram-negative bacteria that constitutes 3–5% of the gut microbial community. The
paper also highlights the various mechanisms by which this bacterium might
exert its effect (Everard A et al. (2013), PNAS)
The study shows
dramatic decrease in gut A.muciniphila in
diet induced obese mice. On restoring the abundance of this strain in obese and
diabetic mice it was found that viable A. muciniphila controls gut barrier
function, fat mass storage, and glucose homeostasis via several mechanisms. This
study identified an association of obesity with a decrease in mucus thickness
that is characteristic of obesity and associated disorders. Interestingly, the
authors found that A. muciniphila restored
this mucus layer. Strikingly, viable A.
muciniphila induces these effects, whereas heat-killed A. muciniphila did not protect the mice from diet-induced obesity
and associated disorders. One of the other key findings was that treatment with
this bacteria led to increase in acylglycerol levels more specifically 2-OG and
2-AG. Incidentally, 2-OG is known to stimulate intestinal L cells which lead to
secretion of GLP-1 (Hansen KB, et al. (2011), J Clin Endocrinol Metab 96(9):E1409–E1417).
GLP-1 is known to increase insulin secretion. Also, A. muciniphila treatment completely reversed diet-induced fasting
hyperglycemia via a mechanism that was associated with a 40% reduction in
hepatic glucose-6-phosphatase expression thereby suggesting a reduction in
gluconeogenesis. Hence this association might point to how A. muciniphila exerts its effects on glucose homeostasis.
Many bacteria (Lactobacilus
spp, Bifidobacterium spp etc.) have been shown to have effect on fat mass
development during diet induced obesity (Fåk F, Bäckhed F (2012), PLoS ONE 7(10):e46837).
However, in this study the emphasis was to study the bacterial strain that is
affected during obesity and type 2 diabetes in humans and rodents. It would be interesting
to see how this development would enthuse the world of gut microbiome research
and interest the pharmaceutical/biotech companies to invest in this field which
would then pave the way for not only treatment but prevention of inflammatory,
lifestyle and even mental diseases in the near future.
