Date of Degree Completion
Master of Science (MS)
Second Committee Member
April K. Binder
Third Committee Member
Kristina A. Ernest
Type 1 Diabetes (T1D) is a polygenic and multifactorial disease, traditionally attributed to genetic susceptibility and diet. Over the past decade, novel studies have placed a higher significance on the role of gut microbiome in T1D pathogenesis. Furthermore, diabetic mouse models have shown higher incidence of T1D in females compared to males, attributed to the differences in gut microbial community structure. Interestingly, female mouse models elicit male-like protection from T1D when transplanted with the male gut microbiome. In a previous study, we observed that female Non-obese diabetic (NOD) mice implanted with slow release 5��-Dihydrotestosterone(DHT) for 90 days showed improved glucose tolerance when compared to untreated females. We hypothesized that DHT treatment alters female gut microbial profile to resemble a male-like gut microbiome that induces improved glucose tolerance, a determinant of T1D protection. We compared the gut microbiome composition of DHT-treated female mice with placebo-treated females and age-matched males to identify and characterize changes in the gut microbiome. Extracted bacterial DNA from intestinal samples were subjected to 16S rRNA sequencing. Sequence reads were analyzed using MicrobiomeAnalyst and Piphillin, two web-based programs for phylogenetic and functional analysis. We identified a significant increase in Bacteroides acidifaciens in DHT-treated females, which can potentially improve glucose tolerance and attenuate T1D. Additionally, we noticed strong similarity trends in the proportional composition of the most abundant taxa between DHT-treated females and age-matched males. Our study shows that DHT-treatment alters the female gut microbial profile to resemble a male-like microbiome and possibly induce improved glucose tolerance, a determinant of T1D protection.
Shrestha, Bikesh, "Effects of 5𝛂-Dihydrotestosterone (DHT) on Mouse Gut Microbiome– A Study of Sex Differences and Hormonal Effects on Gut Microbiome Composition" (2019). All Master's Theses. 1188.
Available for download on Wednesday, June 30, 2021