University Events

Description: TITLE : Application of random forest to predict microbiome markers on clinical outcomes

DATE: Monday, July 29, 2019

TIME: 8:30 AM

LOCATION: TXT-219

Abstract:
Alzheimers disease (AD), the most common cause of dementia, has long been associated with bacterial infections and inflammation-causing immunosenescence. Recent studies examining the intestinal microbiota of AD patients revealed that their microbiome differs from that of subjects without dementia. Application of random forest classification identified clinical parameters as well as numerous microbial taxa and functional genes that act as predictors of AD dementia in comparison to elders without dementia or with other dementia types. We further demonstrate that stool samples from elders with AD can induce lower P-gp expression levels in vitro than those samples from elders without dementia or with other dementia types. We observed that the microbiome of AD elders shows a lower proportion and prevalence of bacteria with the potential to synthesize butyrate, as well as higher abundances of taxa that are known to cause proinflammatory states. Therefore, a potential nexus between the intestinal microbiome and AD is the modulation of intestinal homeostasis by increases in inflammatory, and decreases in anti-inflammatory, microbial metabolism.

In a TB treatment study where the participants were randomized to receive treatments (either NTZ or HRZE) for 14 days, we first show that treatment with NTZ significantly perturbs the intestinal microbiome, with about half of volunteers becoming dominated with single clades of intestinal pathobionts. Second, we demonstrate that HRZE treatment for Tuberculosis, as previously described in cross sectional studies, has a narrow effect on the intestinal microbiome even after 2 weeks of treatment. Third, we show that changes in peripheral gene expression after 2 weeks of HRZE treatment are solely the result of anti-tubercular activity of the HRZE, rather than a com- bination of anti-tubercular activity and microbiome alterations. In fact, we demonstrate that in the NTZ cohort, there are no significant changes paraphernal gene expression after 2 weeks of profound alterations in the intestinal microbiome. Finally, we describe the microbiome-specific dynamics predicting why some individuals are dominated while taking NTZ, whereas others seem to be less affected. Collectively, these results challenge the notion that microbiome alterations have significant impacts at least on peripheral gene expression, limiting the extent to which one could conclude that the microbiome has systemic alterations on the host.

Advisors: Dr. Vanni Bucci, Department of Bioengineering, UMD

Committee members: Dr. Hua (Julia) Fang, Department of Computer & Information Science, UMD;
Dr. Alfa R.H. Heryudono, Department of Mathematics, UMD; Gaurav Khanna, Department of Physics, UMD

All EAS students are encouraged to attend and all interested parties invited.

For further information, please contact Dr. Vanni Bucci or by email vbucci@umassd.edu