Connecting Gut Bacteria and Extra-Intestinal Cancer

My veterinary background in Comparative Medicine at MIT and postdoctoral training from Harvard School of Public Health provided me with expertise in animal models, integrated with a global perspective on human health. My research lab has been funded by NIH R01 and other grants and leverages mouse models that provide unique insights and enable proof-of-concept experiments not easily testable in human subjects. More recent work from my lab translates our data from bench-to-bedside, and recent grants focused on testing the gut-brain axis in human subjects. Among many contributions, I foresaw decades ago that conditions of the gastrointestinal tract may lead to profound systemic outcomes. Our lab did some of the earliest research that connected GI tract bacteria to progression of cancers in distant tissues, such as breast and prostate cancers in mice. I have also made fundamental contributions toward our understanding of probiotic bacteria and their biological impact. My work provides quantitative data for phenotypes that include fertility, longevity, and resistance to obesity. Most animal model phenotypes are integrated mechanistically with a gut-brain axis. In this way, we have shown that early life interventions with microbiota have health-protective effects in later generations. 

Research Support

  • ·R01 CA108854 07: Role Of Il10 And Tgfb1 In Colon Cancer; Pi: Erdman, 
  • U01 CA164337: Gi Tract Dysbiosis And Breast Cancer; Pi: Erdman, Susan 
  • Es002109 32: Pilot Project Program, Cehs; Pi: Erdman, Susan And Alm, Eric 
  • DOD:W81XWH-05-1-0460: Are Anti-Inflammatory Lymphocytes Able To Induce Remission Of Breast Cancer?; Pi: Erdman, Susan
  • Templeton Foundation: “Microbiome-mediated Oxytocin Release in Human Health”; PI: Erdman, Susan
  • Private Foundation: "Probiotics for Public Health"; Co-PI: Erdman, Susan
  • NIH/Mice Microbiome Metabolic Research Program 18AU3951:  “Microbiome and Obesity” PI: Erdman, Susan

Collaborations

  • Cancer Prevention Institute
    of California
  • Columbia University
  • Harvard Medical School
  • MIT
  • Thessoliniki University
  • U. Mass Medical, MA
  • Yale University, CT 
  • Dana Farber, MA
  • University of California Davis
  • Using Rag2-deficient mice lacking lymphocytes, we determined that mammary cancer arose from intestinal microbe–triggered innate immune systemic events requiring pro-inflammatory cytokines such as Tumor necrosis factor (TNF)-alpha. 
  • Mammary tumors in this mouse model matched prior findings in women with elevated inflammatory cytokine levels and poor breast cancer outcome, and also correlated with the lower risk of breast cancer seen in women treated with anti-inflammatory drugs.
  • We went on to show, using a widely applied adoptive cell transfer system in mice, that anti-inflammatory CD4+ regulatory T cells (TREG) inhibited and suppressed this microbe-induced carcinoma while down-regulating systemic carcinogenic inflammatory responses. 
  • Putting forth this systemic model linking bowel microbes and beneficial TREG inhibiting distant cancers challenges the existing paradigm for roles of TREG in cancer.
  • On the surface, our findings on TREG cells appear paradoxical, contrasting with widely held beliefs that TREG cells function in cancer mainly to suppress protective anti-cancer T cell responses. In fact, recent evidence suggests that in vivo, as different TREG cell subsets participate in a sophisticated systemic balancing act of beneficial host functions to maintain homeostasis.
  • We have subsequently investigated larger questions of why breast cancer risk is increasing in developed countries with more rigorous hygiene practices, and how chronic use of prescribed antibiotics may enhance the risk for breast cancer in women.
  • We demonstrated with lymphocyte titration experiments an increase in the anti-neoplastic potency of TREG after prior exposures to H. hepaticus bacteria.  Recent experimental evidence suggests that microbial infections in early life do indeed up-regulate functions that serve to inhibit deleterious disease processes later in life.
  • Our data helps explain the apparent public health paradox in the context of the ‘‘hygiene hypothesis’’ theory: decades of data have shown that early-life infections reduce the incidence of inflammatory disorders such as asthma. Targeted stimulation with bacteria may protect against inflammation-associated pathology, and significantly reduce the risk of cancer later in life.
  • Following this reasoning, even pathogenic bacterial infections may not be entirely adversarial and may impart some long-term health benefits by reducing risk for chronic debilitating diseases, such as autoimmunity and cancer.