Infectious Diseases Associated With the Development and Progression of Specific Cancers

Helicobacter Pylori (H. pylori)

H. pylori is recognized as a major causative agent in the development of gastric cancer and while present in 50% of the world's population only 2% will develop gastric cancer. It is the most widespread chronic bacterial infection, and often infections are asymptomatic and go undetected. It is associated with chronic gastritis, peptic ulcers, gastric cancer and gastric associated lymphoid tissue lymphoma.

The natural home of H. pylori is exclusively the stomach, and as in other persistent pathogens, infections can occur at an early age and persist into adulthood. It is transmitted via contaminated water and via fecal-oral, or oral-oral pathways between people.

Its prevalence has diminished with better sanitation and improved socioeconomic situations, but it is still common in developing countries.

Up until the 1980s it was believed that the stomach was a sterile environment until H. pylori was recovered from biopsies of gastritis and peptic ulcer patients, indicating that treatment could potentially eradicate it, and cure these diseases. A decade later it was shown that H. pylori was also associated with the development of gastric cancers.

In H. pylori there are two main strains, one of which is associated with higher risk of gastric cancer. That strain has a specific genetic code, cag pathogenicity island, cag PAI. This component imparts the strain with the ability to create a bacterial oncoprotein that can transform a normal cells into a tumor cells as well as supporting proinflammatory damage and producing oncogenic stimulating proteins.

When H. pylori invades the stomach it creates a neutral microenvironment around the bacteria which protects it and allows growth. As noted earlier, it may colonize the stomach, not produce symptoms and go undetected for extended periods of time. However, clinically it can cause inflammatory symptoms to develop which include severe indigestion, ulcer disease, or severe heartburn and reflux, and gastric cancer, benign gastric polyps and autoimmune gastritis. Also with chronic gastric irritation damage can occur to the glandular cells causing low secretion of hydrochloric acid and secondarily malabsorption of nutrients and importantly Vitamin B12.

In clinically symptomatic people, testing is indicated with the intention of treating to prevent or reduce symptoms and eliminate high risk strains. Stomach endoscopy provides a direct visualization to correlate disease and symptoms, but it is not completely accurate for assuring the diagnosis of H. pylori. Breath testing in which patients drink radioactive labeled citric acid which then can be measured in the breath is considered the best indicator. 

Treatment Perspectives

In Western Medicine there are protocols that have improved eradication, but require multiple drugs taken 3-times daily. The Initial treatment failure occurs in 15-20% of people, and the chances of success decreases with each new regime that is used for treatment. Antibiotics assist the immune system in clearing the bacteria but unsuccessful treatment occurs because H. pylori releases effector proteins in its host cells that suppress the immune response, as well as adapting to the environmental milieu by adjusting growth and proliferation. In addition, H. pylori can create a protective biofilm shielding it from antibiotics.

Some failures to eradicate often are due to antibiotic resistance, but often compliance with taking three different drugs multiple times a day is difficult. With serious illness treatment can become necessary and requires expertise to manage drug combinations.

In Integrative Medicine, practitioners are using advanced stool testing called polymerase chain reactions (PCR) which amplify DNA sequences to recognize GI pathogens. These include bacteria, GI viruses, candida, and parasites. The available evaluation also provides information on GI inflammation and immune strength, gluten antibodies, the presence of digestive secretions needed and supportive GI needed nutrients. In H. pylori, stool studies can also identify the virulent factor genetic proteins (discussed above), associated cancer risk and susceptibility to treatment antibiotics. 

Offering treatment combining Western and Integrative care might provide potential opportunities for greater success in H. pylori treatment.

Fusobacterium Nucleatum

Fusobacterium nucleatum is an inhabitant of the oral cavity. It is a gram negative anaerobic bacteria that is associated with colorectal cancer development, proliferation and invasion. It is generally considered a normal part of the GI microbiome but can become potentially become pathogenic. In GI disease, patients with Irritable bowel, inflammatory bowel disease and small intestine bacterial overgrowth commonly have this bacteria which can transition into a potential pathogen. 

When pathogenic it begins excessive proliferation, suppresses immune function, stimulates inflammation and creates reactive oxygen species that damage DNA. It directly affects GI function by creating protective biofilms, damaging the epithelial lining causing leaky gut, allowing penetration to deeper intestinal layers. 

It can be diagnosed by stool PCR testing which, if present in substantial amounts in the context of disease, should be considered pathogenic. It also can be tested for in periodontal disease with dental microbiome testing.

Treatment tools available for therapies should focus on any of the underlying diseases listed but often with abnormal stool testing there are other imbalances that need correction. Overall GI balance uses the 4R protocol; remove harmful microbes, replace needed nutrients or digestive aids, re-innoculate with appropriate prebiotic and probiotics, and repair any damaged or injured mucosa. Also natural antimicrobials and biofilm busters help remove pathogens while balancing the entire GI system.

In Chinese medicine, diagnostically SIBO, irritable bowel and inflammatory bowel disease are considered damp heat in the intestines; meaning inflammation often with diarrhea or constipation with the patterns of immune imbalance, or Wei Qi imbalance and poor drainage of the intestine implying fluids no being absorbed and distributed throughout the body. Treatments using acupuncture and individualized Chinese herbal formulas are helpful. There are multiple herbal formulas to correct and rebalance the GI system.

It is important to recognize that this bacteria does not occur in an isolated environment. If chronic GI or periodontal disease is present, a proactive preventive approach, especially with a family history of colon cancer, consideration for testing and treatment is essential to reduce microbial disturbances that can contribute to the development of colorectal cancer.

Salmonella Enterica Serovar Typhi 

Salmonella Typhi is an aerobic gram negative bacteria that is responsible for Typhoid Fever. It is spread from contaminated food, from poor hygiene, often involving food handlers and water contamination. It invades the intestinal lining and then spreads to other organs. Initially it has symptoms of an acute virus with stomach ache, chills, muscle aches, sore throat and fever. It is diagnosed with lab testing but If not diagnosed quickly it can be life threatening. 

One to four percent, even with treatment, become asymptomatic carriers potentially spreading infection and some carriers colonize their gallbladder causing chronic asymptomatic inflammation and predisposing to gallbladder cancer. 

The action of this bacteria as a cancer initiator is associated with its production of a toxin, typhoid toxin. It creates local chronic inflammation causing DNA damage which alters normal cellular replication in infected toxic cells. Infected cells also surround themselves with a bio protective film that supports persistent infection, decreases immune accessibility and allows continued bacterial growth and toxic exposure.

Dental Infection

Porphyromonas Gingivalis

This is a gram negative oral anaerobe pathogen found in the mouth and associated with gum disease. It travels from the mouth into the GI tract where it settles in the colon where it can disrupt the normal microbiome and can promote a microenvironment that supports tumor growth. It remains in the colon by evading the immune system’s response, creating chronic inflammation and initiating epigenetic colon mutations. It is also capable of dysregulating normal cellular DNA replication by manipulating the MAPK/ERK pathway within the colon cell nucleus that regulates cell proliferation. 

And while clinical studies are still inconclusive as to its initiation of cancer, in patients with colon cancer, P gingivalis is found in their microbiota. It has been shown in animal studies to increase the severity of inflammatory bowel disease. Appropriate dental hygiene and/or oral microbiome testing can uncover this pathogen so treatments can be instituted to reduce its presence.

Fusobacterium Nucleatum

This is a gram negative anaerobe that is ever present in the oral cavity of people in good health and those with chronic disease. It is associated with oral gingival infections and in certain situations, though rare, is implicated in GI disorders such as colorectal cancer and inflammatory bowel disease, adverse pregnancy outcomes rheumatoid arthritis and Alzheimer's disease.

In the mouth it causes aggressive periodontitis, gingivitis and damage to the pulp, the interior of teeth and its presence is made worse in smokers.

Current technology can provide testing of the oral microbiome, and these bacteria. If present oral probiotics can be used to shift the microbiome toward beneficial bacteria and thereby reducing these pathogens. Oral health with brushing, flossing and using a water pic also offer preventative benefits by reducing plaque and gum inflammation.