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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2019)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women worldwide. In addition to infertility, many women with PCOS have metabolic abnormalities that result in an increased risk of type 2 diabetes and cardiovascular disease. Although the etiology of PCOS is poorly understood, accumulating evidence suggests that androgen excess is an important contributor to the pathogenesis of PCOS. The human large intestine contains a complex community of microorganisms (the gut microbiome) important for human health and disease. Studies have shown that the gut microbiome is altered in humans with metabolic disorders such as obesity and type 2 diabetes, and that the gut microbiome may be a causal factor in the development of these disorders. Dysbiosis of the gut microbiome has been proposed to factor in the development of PCOS and studies have shown that changes in the gut microbiome are associated with PCOS in women and in rodent models. However, it is unknown if the gut microbiome plays a causal role in the PCOS phenotype. For this dissertation I used human fecal samples and a letrozole-induced PCOS mouse model together with 16S rRNA gene sequencing to further our understanding of the effects of androgen excess and the role of the gut microbiome in PCOS. Using human fecal samples and patient clinical parameters, the results in chapter 1 suggest that androgen excess may play a critical role in altering the gut microbiome in women with PCOS. Since there is considerable variation in the human gut microbiome due to differences in diet and ethnicity, chapters 2 and 3 used a PCOS mouse model to gain more insight into the pathophysiology of PCOS. The results from chapter 2 indicate that dysregulation of the metabolism and gut microbiome in PCOS may be influenced by the timing of androgen exposure. Lastly, the results from chapter 3 showed that exposure to a healthy gut microbiome improved the metabolic and reproductive phenotype in a PCOS mouse model. Overall, these results suggest that modulating the composition of the gut microbiome may be a potential treatment option for women with PCOS.

    Cover page: Role of the Gut Microbiome in Polycystic Ovary Syndrome
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2015)
    Clinical manifestations of pancreatic cancer often do not occur until the cancer has undergone metastasis, resulting in a very low survival rate. In this study, we investigated whether salivary bacterial profiles might provide useful biomarkers for early detection of pancreatic cancer. Using high-throughput sequencing of bacterial small subunit ribosomal RNA (16S rRNA) gene, we characterized the salivary microbiota of patients with pancreatic cancer and compared them to healthy patients and patients with other diseases, including pancreatic disease, non-pancreatic digestive disease/cancer and non-digestive disease/cancer. A total of 146 patients were enrolled at the UCSD Moores Cancer Center where saliva and demographic data were collected from each patient. Of these, we analyzed the salivary microbiome of 108 patients: 8 had been diagnosed with pancreatic cancer, 78 with other diseases and 22 were classified as non-diseased (healthy) controls. Bacterial 16S rRNA sequences were amplified directly from salivary DNA extractions and subjected to high-throughput sequencing (HTS). Several bacterial genera differed in abundance in patients with pancreatic cancer. We found a significantly higher ratio of Leptotrichia to Porphyromonas in the saliva of patients with pancreatic cancer than in the saliva of healthy patients or those with other disease (Kruskal-Wallis Test; P < 0.001). Leptotrichia abundances were confirmed using real-time qPCR with Leptotrichia specific primers. Similar to previous studies, we found lower relative abundances of Neisseria and Aggregatibacter in the saliva of pancreatic cancer patients, though these results were not significant at the P < 0.05 level (K-W Test; P = 0.07 and P = 0.09 respectively). However, the relative abundances of other previously identified bacterial biomarkers, e.g., Streptococcus mitis and Granulicatella adiacens, were not significantly different in the saliva of pancreatic cancer patients. Overall, this study supports the hypothesis that bacteria abundance profiles in saliva are useful biomarkers for pancreatic cancer though much larger patient studies are needed to verify their predictive utility.
      Cover page: Characterization of the salivary microbiome in patients with pancreatic cancer
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2019)

      Background

      A majority of women with polycystic ovary syndrome (PCOS) have metabolic dysfunction that results in an increased risk of type 2 diabetes. We previously developed a pubertal mouse model using the aromatase inhibitor, letrozole, which recapitulates many of the reproductive and metabolic features of PCOS. To further our understanding of the effects of androgen excess, we compared the effects of letrozole treatment initiated in puberty versus adulthood on reproductive and metabolic phenotypes as well as on the gut microbiome.

      Results

      Letrozole treatment of both pubertal and adult female mice resulted in reproductive hallmarks of PCOS, including hyperandrogenemia, anovulation and polycystic ovaries. However, unlike pubertal mice, treatment of adult female mice resulted in modest weight gain and abdominal adiposity, minimal elevation in fasting blood glucose and insulin levels, and no detectable insulin resistance. In addition, letrozole treatment of adult mice was associated with a distinct shift in gut microbial diversity compared to letrozole treatment of pubertal mice.

      Conclusions

      Our results indicate that dysregulation of metabolism and the gut microbiome in PCOS may be influenced by the timing of androgen exposure. In addition, the minimal weight gain and lack of insulin resistance in adult female mice after letrozole treatment indicates that this model may be useful for investigating the effects of hyperandrogenemia on the hypothalamic-pituitary-gonadal axis and the periphery without the influence of substantial metabolic dysregulation.
        Cover page: Letrozole treatment of adult female mice results in a similar reproductive phenotype but distinct changes in metabolism and the gut microbiome compared to pubertal mice
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2020)
        The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.
          Cover page: The urgent need for integrated science to fight COVID-19 pandemic and beyondCreative Commons 'BY' version 4.0 license
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