Short summary

Recent research strongly suggests that gastrointestinal tract microbiota (the collected sum of bacteria and virus) can modulate several diseases, including autoimmune diseases and cancer. The negative effects of a hazardous microbiota milieu could be reverted by side-effect-free, non-invasive changes in lifestyle, diet and/or probiotic supplements, if identified early. 

The goal is to discover novel gut metagenomic biomarkers to identify individuals at high risk of developing breast cancer. We will compare the gut bacteria microbiota of breast cancer patients and mammography-cleared healthy controls. 

Rationale

Background

There is a vital and complicated bidirectional relationship between the human intestinal microbiota and its host, and knowledge of this inter-dependency is emerging that encompasses not only the tissue in direct contact with the microbiota, but also distant sites, such as breast tissue. 

The establishment of human microbiota occurs very early in life, and the exposure to bacteria subsequent to natural birth (vs. caesarian) has been proposed to provide life-long protection against allergies, autoimmune diseases and cancer, all associated with immune competency. Even before birth, microbiota may be influenced, as shown by studies in rodents wherein transgenerational effects of maternal estrogen changes are believed to influence the offspring's immune system and disrupt T-cell differentiation, including Treg T cells. This may lead to increased sensitivity to chemical carcinogenesis and increased age-related spontaneous cancer. Even when the microbiota remains unaltered, the infant microbiome is significantly different from that of the third year of life, in which the microbiota is more similar to adults. In the aged adults, the microbiome tends to be of a pro-inflammatory phenotype with increased potential for DNA damage etc. 

A less diverse microbiome has generally been identified for pathological conditions, including breast cancer. 

An important strain of the Proteobacteria phylum, contributes to the maturation of killer T-cells, which are important immune cells capable of eliminating foreign antigens and breast tumor cells. 

Manipulation of the microbiota composition is possible, and it is highly influenced by our diet, as shown by a study that reported composition changes within 24 hours of diet change. The participants' microbiota returned to baseline upon cessation of the restricted diets, and epidemiological studies of the increasing incidence of breast cancer in Asians highlight the effects of a change to a more western lifestyle and diet. 

Hypothesis

Human fecal microbiota is altered in women with breast cancer compared to a mammography-cleared control group, and thus may be an indicator of breast cancer.  

Aims

1) Collect stool samples from breast cancer patients and from breast cancer cases (n=100) and matched healthy controls (n=150).

2) Analyze the microbiome of breast cancer patients and healthy controls to identify differences in bacterial profiles. 

Description of the cohort

Breast cancer patients (women) of all ages (N=100), as well as a healthy control group participating in the Danish biennial mammography screening program (N=150).

Data and biological material

Stool, blood samples, tumor tissue, questionnaires

Collaborating researchers and departments

Department of Oncology, Odense University Hospital; Department of Cancer and Inflammation Research, University of Southern Denmark

• Professor Henrik J. Ditzel

Department of Oncology, Odense University Hospital

• Annette Raskov Kodahl
• Katrine Søe

Department of Cancer and Inflammation Research, University of Southern Denmark

• Sidse Ehmsen

Department of Pathology, Odense University Hospital 

• Maria Lyng
• Anne Marie Bak Jylling

Publications associated with the project