(A Tale of Two Mice)
Weight Loss and Gut Microbes: the (well-deserved!) reigning poster child of human microbiome research.
The story of how gut microbes impact host weight began at Washington University in Jeffrey Gordon’s Lab. In 2005, PNAS* published Ruth Ley’s “Obesity alters gut microbial ecology.” Ley, a post-doc in Gordon’s Lab, noted that certain gut microbes produce a variety of enzymes that enable the human host to extract calories from polysaccharides (think starch-rich foods, like potatoes). Without these microbes, humans are not able to digest many complex starches. Ergo, people predisposed to obesity may have über calorie-extracting microbes! Ley and members of Gordon’s Lab analyzed more than 5,000 gut bacterial genome sequences from the intestines of genetically obese mice (ob/ob mice) and their lean, wild-type siblings. The ob/ob mice eat excessively and develop obesity, high blood pressure, and increased insulin. Compared with their lean counterparts, ob/ob mice had a distinct microbiota, exhibiting a 50% decrease in Bacteroidetes abundance and a comparative increase in Firmicutes abundance.
Bigplankton @ en.wikipedia
(An ob/ob mouse and wild-type mouse)
Bacteria belonging to the Firmicutes or Bacteroidetes phylum* dominate both the mouse and human gut microbiota. Did the Firmicutes contribute to the ob/ob mouse’s efficient caloric/energy harvest and increased adiposity? Another post-doc, Peter J. Turnbaugh, further examined the ob/ob microbiome in a 2006 Nature paper entitled “An obesity-associated gut microbiome with increased capacity for energy harvest.” Using sequencing and comparative metagenomics, Turnbaugh found that the ob/ob microbiota contained higher levels of methanogenic microbes*** that increase bacterial fermentation efficiency, contributing to mouse adiposity. In addition, the ob/ob microbiome contained enriched DNA sequences of enzymes and proteins involved in microbial starch digestion. Next, the team transplanted either a wildtype or ob/ob microbiome in germ-free mice. Both groups of mice were maintained on the same diet. Two weeks after transplant, the mice that received the ob/ob microbiome had a higher abundance of Firmicutes and a greater increase of body fat percentage, compared with the mice that received the “normal” microbiome. Very cool. Perhaps future diets will include a serving of lean microbiome!
In 2013, I spent a summer interning at Turnbaugh’s Lab examining the role of antibiotics and diet on the gut microbiota. It was a wonderful experience that solidified my interest in pursuing microbiology for grad school. For more information, check out some of the amazing research at Jeff Gordon’s lab (WU), Ruth Ley’s Lab (Cornell), and Peter Turnbaugh’s lab (UCSF).
For a similarly awesome Microbiota and Obesity story: check out this image and the last link below
From: Walker, Alan W., and Julian Parkhill. “Fighting obesity with bacteria.” Science341.6150 (2013): 1069-1070. Reprinted with permission from AAAS.
*Proceedings of the National Academy of Sciences of the United States of America. Established in 2007, PNAS Online publishes all PNAS articles from 1915 to the present. This is a great source for free, peer-reviewed articles.
** Remember King Philip Came Over for Ginger Snaps (Classification System: Kingdom, Phylum, Class, Order, Genus, Species)? Bacteriodetes: gram-negative, rod-shaped bacteria // Firmicutes: typically gram-positive and are usually rod-shaped or circular.
*** these archaea methanogens produce methane and derive energy from carbon dioxide.
Sources + Additional Information: