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Publication
Incorporation of therapeutically modified bacteria into gut microbiota inhibits
obesity.
Authors Chen Z, Guo L, Zhang Y, L Walzem R, Pendergast JS, Printz RL, Morris LC,
Matafonova E, Stien X, Kang L, Coulon D, McGuinness OP, Niswender KD, Davies SS
Submitted By Sean Davies on 7/21/2014
Status Published
Journal The Journal of clinical investigation
Year 2014
Date Published
Volume : Pages 124 : 3391 - 3406
PubMed Reference 24960158
Abstract Metabolic disorders, including obesity, diabetes, and cardiovascular disease,
are widespread in Westernized nations. Gut microbiota composition is a
contributing factor to the susceptibility of an individual to the development of
these disorders; therefore, altering a person's microbiota may ameliorate
disease. One potential microbiome-altering strategy is the incorporation of
modified bacteria that express therapeutic factors into the gut microbiota. For
example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the
N-acylethanolamide (NAE) family of lipids, which are synthesized in the small
intestine in response to feeding and reduce food intake and obesity. Here, we
demonstrated that administration of engineered NAPE-expressing E. coli Nissle
1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in
mice fed a high-fat diet. Mice that received modified bacteria had dramatically
lower food intake, adiposity, insulin resistance, and hepatosteatosis compared
with mice receiving standard water or control bacteria. The protective effects
conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their
removal from the drinking water. Moreover, administration of NAPE-expressing
bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight
gain. Our results demonstrate that incorporation of appropriately modified
bacteria into the gut microbiota has potential as an effective strategy to
inhibit the development of metabolic disorders.




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