Microbiome Linked to Hyperthyroid Disorders, Cancer, and More

Written by W. Todd Penberthy

Since 80% of the immune system response to the environment is driven by bacterial ecosystems, a healthy gut microbiota may have a profound effect on the body’s immunity, influenced by neurotransmitters like gamma-aminobutyric acid (GABA),1 according to Jack Gilbert, PhD, who presented on the role of the microbiome in thyroid cancer at the 38th annual meeting of the American Association of Endocrine Surgeons.

“In fact, the reciprocal nature of a healthy microbiome in the human gut fosters an interaction with many physiological processes that regulate immune function and metabolic homeostasis,”1 said Dr. Gilbert, the Orlo & Carol Clark Distinguished Lecturer in Endocrine Surgery and director of the Microbiome Center at the University of Chicago in Illinois.

"For many in the microbiome research community, illness represents a loss of health-promoting commensal microbes with an overgrowth of pathogenic bacteria (dysbiosis),” said Dr. Gilbert, "which may explain an increased susceptibility to thyroid disorders, diabetes, cancer, sepsis, and maybe even depression, due to altered GABA levels."1,2

“Fortunately, treatments may soon be available to restore a desirable microbial ecosystem given the very favorable experimental results to date,” he said. In support of the microbiome thesis, an analysis of asthma rates in 2 similar communities of children: the Amish and the Hutterites, was conducted.3

“Both cultures were dependent on farming. Whereas the Amish had personal family farms,where the children were encouraged to interact with the land in their farm work, increasing their exposure to hoofed animals, crops, and soil,” said Dr. Gilbert, “the Hutterite children were not allowed on the farms for health and safety reasons; and, their farms were more technologically driven.”

The prevalence of asthma among the Amish children was 5.2% versus 21.3% for the Hutterites, and allergic sensitization was 7.2% and 33.3%, respectively.3

“Hematological and Omics analyses revealed that the neutrophils in the Amish children were younger, while the Hutterite children had more eosinophils, which is characteristic of allergic sensitization,3,4  Dr. Gilbert told EndocrineWeb.

“In experiments using dust extracts derived from both communities, the soil from the Amish farms appeared to exert a protective effect in upper airway hyper-responsiveness in ovalbumin mouse models, leading the researchers to conclude that early exposure to animals and soil may exert lifelong beneficial effects on the immune system,”3 said Dr. Gilbert.

This connection has been supported by other studies in which fewer and less severe atopic disorders have been documented in communities having an increased environmental exposure to pathogen-associated molecular patterns.5,6

Clinical trials are underway using microbiota-based therapies to treat C. difficile infections, sepsis, and irritable bowel infections,7-9 according to Dr. Gilbert. 

“Fecal material transfer (FMT) is the most well-established and developed therapeutic option to effectively manage C. difficile colitis, especially if it is recurrent or refractory to antibiotics, but data on long-term outcomes is not yet available,” said Dr. Gilbert. 

“We know exactly what these bacteria do, and there are companies in the process of testing microbial therapies to treat C. difficile infections, irritable bowel syndrome, and sepsis, but the evidence indicates that there are going to be many more indications in the future,” Dr. Gilbert told EndocrineWeb.

The predominance of particular bacterial species can affect the susceptibility to hyperthyroid disorders or papillary thyroid cancer.10,11

“Approximately 90% of hyperthyroid disorders have an autoimmune component likely triggered by microbiome dysbiosis,”1 said Dr. Gilbert. “Moreover, hyperthyroidism has been linked to decreases in Bifidobacterium and Lactobacillus, but with increases in Enterococcus presumably via thyroid-reactive antigenic molecular mimicry.”10

“In the California Teacher’s Study, which made a case for a significant reduction in risk of developing papillary thyroid cancer as an adult following exposure to a rural setting during early childhood,”11 said Dr. Gilbert, “These findings are consistent with the hygiene hypothesis, which postulated that certain microbial exposures may be important in priming the immune system.”12

Studies have shown that diabetic patients typically have a less diverse microbial community.4 Fecal material transplants from lean healthy patients to patients with type 2 diabetes treated with antibiotic have been shown to improve insulin sensitivity.13

“The pertinent takeaway is that this diversity is essential for aiding in digestion and helping the body produce short-chain fatty acids that regulate glucose levels,” he said.

In a metabolic study, it was previously known that a lipopolysaccharide endotoxin was the only known bacterial product associated with obesity and insulin resistance in murine animal models of obesity,14 said Dr. Gilbert. Investigators were able to single out one bacterial species, Enterobacter cloacae B29, linked to mice that became obese.14

“Moreover, in research performed in the Netherlands, Dr.  Nieuwdorp has shown that lean male donor fecal microbiota transplantations to males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity” 1,5 Dr. Gilbert said.

Dr. Gilbert formed a company to accelerate the development of defined microbial probiotic formulations.

“The company, Gusto, currently has identified 12 potentially therapeutic strains for use in controlling sepsis future clinical microbiota-based therapies,” Dr. Gilbert told EndocrineWeb.

Sources

  1. Gilbert J. Thyroid Cancer and the Microbiome. Presented at: American Association of Endocrine Surgeons (AASE) 2017 annual meeting on April 3, 2017; Orlando, Florida.
  2. Francino MP. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol. 2016;12;6:1543.
  3. Stein MM et.  al.  Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med.  2016; 375(5):411-21. 
  4. Kline JN. Eat dirt: CpG DNA and immunomodulation of asthma. Proc Am Thorac Soc. 2007;4(3):283-8.
  5. Hartstra AV et al. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015;38(1):159-65.
  6. Cash BD. Emerging role of probiotics and antimicrobials in the management of irritable bowel syndrome. Curr Med Res Opin. 2014;30(7):1405-15.
  7. Finkelstein R, Oren I. Sepsis: Antimicrobial Therapy, Sepsis—An Ongoing and Significant Challenge. Azevedo L (ed.), InTechOpen, 2012. Available from: https://www.intechopen.com/books/sepsis-an-ongoing-and-significant-challenge/sepsis-antimicrobial-therapy. Accessed April 10, 2017.
  8. Synthetic Biologics’ C.difficile mid-stage study meets main goal. January 5, 2017. Available at: http://www.reuters.com/article/us-synthetic-study-idUSKBN14P1C2.
  9. Hirsch BE. Saraiya N, Poeth K,et al. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis. 2015; 15: 191.
  10. Kiseleva EP, Mikhailopulo K, Sviridov OV, et al. The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases. Benef Microbes. 2011;2(2):139-54.
  11. Clarke CA, Reynolds P, Oakely-Girvan I, et al. Indicators of microbial-rich environments and the development of papillary thyroid cancer in the California Teachers Study. Cancer Epidemiol. 2015;39(4):548-53.
  12. Stiemsma LT, Turvey SE. Asthma and the microbiome: defining the critical window in early life. Allergy Asthma Clin Immunol. January 6, 2017. Available at: https://aacijournal.biomedcentral.com/. Accessed April 10, 2017.
  13. Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015; 38(1):159-65.
  14. Zhang C1 et al.  Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations.  ISME J.  2012 Oct;6(10):1848-57.
  15. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. 2013;11(9):639-47.