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Designer probiotic supplementation outcomes on high fat diet

University of British Columbia

High fat diets (HFDs) cause insulin resistance, oxidative stress, inflammation, all of which are linked with gut microbial dysbiosis. As a therapy, probiotics can reduce inflammation, oxidative stress and insulin resistance under such conditions. However, for these protective effects, probiotic microbes need to colonize and persist in the gut, especially under conditions of oxidative insult and inflammation. Naturally occurring probiotics have fared poorly thus far. To overcome this challenge, two probiotics, BioColoniz & BioPersist, were created in Dr. Gibson’s laboratory from Lactobacillus reuteri and Escherichia coli Nissle 1917 (EcN) parent strains respectively. BioColoniz is bio-engineered to adhere and colonize the gut while BioPersist possesses a survival advantage by expressing a gene that confers resistance to ambient oxidative insult. We hypothesized that these designer probiotics could improve insulin insensitivity induced by HFDs. C57/Bl6 mice were fed a 40% energy HFD for 6 weeks. Mice were either not gavaged or gavaged with the one of the two probiotics during the study. Subsequently, analysis of BioPersist and Biocoloniz livers revealed lowered oxidative stress biomarker nitrotyrosine. BioPersist livers also demonstrated increased antioxidant (glutathione peroxidase-4) and reduced inflammatory biomarkers (inducible nitric oxide synthase and tumor necrosis factor-α). Mice administered BioPersist also gained the least amount of weight on HFD and demonstrated improved glucose tolerance tests. Improved phosphorylation and abundance of insulin/IGF-I receptor β in both BioPersist and BioColoniz livers were also noted. Furthermore, BioPersist livers had elevated phosphorylation of Akt, a key insulin signaling molecule. Overall, we show an improvement of in vivo glucose homeostasis associated with lower inflammation and oxidative stress in the liver with designer probiotics following a high fat diet. These results indicate that bio-engineered probiotics might be a viable therapeutic option for treating clinical insulin resistance and type 2 diabetes in the future.

Text

2021-08-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/77270

Biochemistry and Molecular Biology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/