Microbes within our bodies may cause or contribute to cancer

By Linda Perrett

Are microbes the likes of bacteria and viruses helpful or hurtful? Do microbes affect each of us differently? Because these questions are still unanswered in several areas of science, researchers are beginning to pay much more attention to these tiny, mostly microscopic, life forms.

Microbes are, indeed, living organisms. Many are just a single cell. Microbes help plants obtain water and nutrients, and provide protection from certain pests and pathogens. Bacteria, one type of microbe, play key roles in the making of cheese, yogurt, and chocolate.

Within our bodies, common microbes outnumber human cells by a ratio of 10-to-1. These microbes, our microbiome, are increasingly thought to be required for normal human development, physiology, immunity, and nutrition. Most are protective or harmless, but some types of microbes are associated with diseases, including cancer. In fact, it is believed that 15 to 20 percent of the cancer cases diagnosed, worldwide, each year may be linked in some way to microbes.

Human Microbiome Project

Until recently, scientists were unable to study the human microbiome, through whole genome sequencing, which is a laboratory process that determines the complete DNA sequence of an organism. This was because only a limited number of microbes, specifically those in the gut, had enough DNA matter to be analyzed through this technology.

Additionally, sequence assembly, which is the process of putting together fragments of sequenced DNA to be studied, was technically challenging because standardized sets of microbe genomes used for reference (genome datasets) were not available for many microbes.

In order to obtain genome sequences for investigators to study, new techniques had to be developed to assess microbes considered uncultivable for study. Hence, NIH established the Human Microbiome Project (HMP).

HMP investigators will sequence, at minimum, 3,000 bacterial genomes that represent the human microbiome. To date, there are more than 1,000 bacterial genomes at various stages of sequencing.

HMP scientists are helping to define the microbiome commonly found in a group of people, as well as working to define the associations between these microbes and various diseases. Just a few areas of early exploration have uncovered findings on the role of: the skin microbiome in psoriasis; the urogenital microbiome in pediatric abdominal pain and intestinal inflammation; and the gut microbiome, where scientists uncovered an association with esophageal adenocarcinoma (esophageal cancer).

The most recent HMP study results appeared in the journal Nature on June 14, 2012. HMP researchers mapped the normal microbial make-up of 242 healthy humans, collecting 11,174 specimens taken from 15 to 18 distinct body sites, over different periods of time. The investigators sorted through and sequenced genomic data from microorganisms, including benign microbes and other pathogenic microbes that are known to cause illnesses. (In healthy individuals pathogens cause no disease; they simply coexist with their host and the rest of the human microbiome.) Researchers are now trying to determine why some pathogens lead to illness, and under what conditions they do so.  See press release. 

As evidence builds that microbes play a major role in health and disease, HMP investigators expect to continue international collaboration, of the type established by the Human Genome Project, to generate rich, comprehensive, and publicly available datasets.

Bacteria and virus sequencing

The majority of HMP genomic studies are on bacteria, in large part because there is no gene common to viruses.

Almost all bacteria share the 16S rRNA gene, making it a common target for sequencing. Since 16S rRNA often exists as a multigene family (a set of several similar genes formed by duplication of a single original gene), it offers additional gene targets for study, which may result in discovery of previously unidentified, or unusual strains, of bacteria.

Not only is there no single gene common to virus genomes, less than 1 percent of microbial hosts associated with viruses have been cultivated, and no systematic databases are available to help with analysis. Still, some HMP scientists are taking first steps in tackling this problem by sharing virus samples they have collected from healthy volunteers, with the goal of producing intact viruses for research.

Bacteria and cancer

Some types of bacteria, particularly within our bowel, protect us against infection. Cancer-associated bacteria, on the other hand, appear to be opportunistic, infecting healthy tissues after cancer has already established itself. Still other types of bacteria have been directly linked to development of cancer; it is not clear how this occurs.

Two well-known examples of bacteria associated cancers include: Helicobacter pylori andSalmonella typhi.

Helicobacter pylori is linked to stomach cancer as well as a type of lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma. Salmonella typhi is linked to some types of gallbladder cancers.

Viruses and cancer

Viruses are the most abundant microbes on the planet. They are commonly known to cause colds, coughs, and sore throats, but some viruses suppress the body’s immune system and cause inflammation that eventually alters a person’s genes, which could ultimately lead to cancer.

Scientists know viruses that cause cancers include: Hepatitis B (HBV), Hepatitis C (HBC), and Human papillomavirus 16 and 18 (HPV 16 and 18).

HBV and HBC are associated with hepatocellular carcinoma, or liver cancer. HPV 16 and 18 are most directly related to cervical cancer while other HPV strains are linked to vaginal, vulvar, anal, and penile cancer; squamous cell carcinoma, a skin cancer; and oropharyngeal cancer, a cancer of the tongue, tonsils, or upper throat.

Other well known viruses associated with cancer are: Epstein-Barr, which may cause Burkitt’s lymphoma; non-Hodgkin lymphoma; and nasopharyngeal carcinoma, a cancer of the throat.

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