Biofilm_Colon Cancer_JHU Study

Colon Cancer, Biofilm, Bacteria, Probiotics Role

SUMMARY: New Colon Cancer, Biofilm, Bacteria, Probiotics ROLE in Colon Cancer findings out of John Hopkins: biofilms are present in 89% of tumors (13/15 cancers & 4/4 polyps) removed from right ascending colon, but only in 12% of tumors on the left side (2/15 cancers and 0 polyps).

Most colorectal cancers are known to develop slowly, over five to 10 years, “and it’s a disease that’s curable if you diagnose it early,”  says Cynthia L. Sears, M.D., professor of medicine and oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health.  Well…  therein lies the rub as the gold standard test,  colonoscopy, many do not do.  Additionally, as discussed in the post,  YOUNG ADULT NEWLY DIAGNOSED COLON & RECTAL CANCER DOUBLES BY 2030,” there is an alarming increase in colon cancer among the young who typically do not have colonoscopy.  

Well…  the ability to test noninvasively may be growing nearer due to recent biofilm findings.  And interestingly, the researchers noted that while probiotics may reduce biofilms, the evidence for reduced risk of colon cancer does not yet exist. 

Colon Cancer, Biofilm, Bacteria, Probiotics Role
Biofilm-positive sample clusters are virtually a universal feature of tumors in the right colon

Johns Hopkins researchers have just demonstrated for the first time, that bacterial biofilms are associated with colorectal cancers, one of the leading malignancies in the United States and abroad.  They found that dense mats of interacting bacteria, called biofilms, were present in the majority of cancers and polyps, particularly those on the right side of the colon.  Bacterial ‘Bunches’ Linked to Some Colorectal Cancers, Dec 16, 2014.  Colon biofilms are dense communities of bacteria encased in a likely complex matrix that contact the colon epithelial cells, and they are nearly universal on right colon tumors.  Link to the study at:  Microbiota organization is a distinct feature of proximal colorectal cancers, study published online Dec. 8 in the Proceedings of the National Academy of Sciences.  The study abstract notes:

“Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota.” 

Their study,  looked at healthy and cancerous tissue biopsied from 118 people undergoing surgery or colonoscopy, found:

Biofilms were present on 89 percent of tumors – 13 of 15 cancers and four of four polyps – removed from the right or ascending colon. By contrast, biofilms, for reasons not known, were found only 12 percent of the time on tumors on the left side of the colon – two of 15 cancers and no polyps. 

The risk of developing colorectal cancer might be five-fold higher in patients with biofilms on the right side of the colon, compared to patients without the bacterial mats.

“What was so striking was that these biofilm-positive samples cluster so dramatically in the right colon,” says Sears. “In fact, it’s virtually a universal feature of tumors that appear in that section of the colon, although we don’t understand why.”

Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa.

Gene Sequencing of Tumor Bacteria both with and without Biofilm

The same species of bacteria were present in tumors from people with and without biofilms. This suggests that the biofilm itself, rather than a particular kind of bacteria, may be the cancer-causing trigger… Over time we recognized that our bacteria triggered changes in cells that were consistent with the ability to induce tumors,” she (Sears) says. “And we wondered whether colonization with these organisms might be a long-term trigger for colon cancer.”

Biofilm, bacteria & probiotics role in colon cancer_JHU Study.
Source: http://www.hopkinsmedicine.org/news/media/releases/bacterial_bunches_linked_to_some_colorectal_cancers. Color-enhanced, electron micrograph image of a biofilm-covered, right-sided colon cancer. Purple coloring shows rod-shaped bacteria embedded in mucus strands (yellow). From PNAS (DOI 10.1073/pnas.1406199111).
Credit: Cynthia Sears, Johns Hopkins
Researchers noted: Probiotic Treatment May Reduce Biofilms but no evidence they reduce Cancer Risk

The research team also noted that probiotic treatments might be one strategy to reduce biofilms, but there is as yet no evidence that their use will reduce cancer risk or should be recommended to the public. Sears and her team speculate that biofilms induce inflammation, which in turn spurs genetic mutations in epithelial cells that make them prone to becoming cancerous. In the study, the scientists found a link between the presence of biofilms and biological changes associated with increased cell growth in the biopsied tissues. – Bacterial ‘Bunches’ Linked to Some Colorectal Cancers, Dec 16, 2014.

There are a lot of probiotic choices out there for you to consider that can be purchased or made at home.   If you are new to eating whole food live probiotics, begin slowly such as a small amount of the juice, proceeding to a few strands of ferment, then to a forkful which typically is all that is needed once to a few times a day.  Think of whole food live probiotics as condiments.  Fermented foods and fermented dairy in fact make up separate sections of my “What Eating Real Whole Food Looks Like” though most people today eat few to no living probiotics beyond perhaps commercial yogurt whose nutrition, additives, quality, and probiotic qualities are questionable:

What Eating Whole Food Looks Like
Slide source biomeonboardawareness.com

The post CLA GRASSFED SCD YOGURT & CYTOKINE STUDIES: ERIVAN & WHOLE FOODS 365 details the How-To’s for making SCD/GAPS lactose free yogurt.  This post also notes some incredible benefits of yogurt such as CLA which can modulate dendritic cell cytokine production which plays a central role in initiating inflammation by directing T helper (Th) cell differentiation…   Though truth be told, science has yet to figure out how or why probiotics work.

Fermented vegetables can also be homemade and How-To directions are my Pinterest board, “Ferments: Vegs & SCD Yogurt (lactose free.)” 

Some ferments that can be purchased ready made are kimchi, sauerkraut, and pickles as shown in the below pic.  The tricky part of purchasing ready made probiotics is understanding that such must be living so do your research.  Generally, look to the refrigerated section for unpasteurized ferments (pasteurization kills probiotics), read the product website, and ask questions.  Some SCD/GAPS living whole food probiotic commercial choices I am aware of are:

Fermented Vegs
Slide source: biomeonboardawareness.com
Test Methods for Colon Cancer

The biofilm finding could very well result in the development of noninvasive testing for colon cancer; the current gold standard is colonoscopy.   Only about sixty percent  of Americans get a colonscopy, and they are less frequently performed outside the United States especially in low-resource countries where colorectal cancers are on the rise.

Additionally, colonoscopy is rarely performed  for the young which is  concerning given the recent finding of an  alarming increase in colon cancer among the young which I posted at:  YOUNG ADULT NEWLY DIAGNOSED COLON & RECTAL CANCER DOUBLES BY 2030.  These researchers are warning physicians to be on the lookout for colon and rectal cancer (CRC) symptoms that might otherwise be dismissed in younger people and only identified as cancer after the disease has progressed.  They noted obvious risk factors for  CRC (lack of screening, obesity, and physical inactivity), but then went and encouraged:

reduced consumption of processed and fast food and more vegetables and fruits to reduce risk.

The study specifics are:

  • The number of young adults (aged 20 to 34, and 35 to 49 years) with newly diagnosed colorectal cancer is anticipated to nearly double by 2030.  
  • For patients under age 34, the increase is across all stages of disease: localized (confined to the colon or rectum), regional (contiguous and adjacent organ spread, such as to the lymph nodes, kidney and pelvic wall) and distant (referring to remote metastases).
  • For ages 20 to 34 years, colon cancer increase is 90.0% and rectal cancer increase is 124.2% by the year 2030.
  • For ages 35 to 49 years, colon cancer increase is 27.7% and rectal cancer increase is 46.0% by the year 2030.

A concern for young patients is that they receive an Irritable Bowel Syndrome (IBS) diagnosis when if fact it may be CRC.  IBS affects up to 15% of the general adult population, and studies to date (here, and here) have not found an association between IBS and CRC.  But the alarming increase coupled with researcher warnings to physicians to be on the lookout for CRC symptoms that might otherwise be dismissed in younger people and only identified as cancer after the disease has progressed, is concerning.

The new biofilm findings discussed in this post may  develop into a noninvasive test that detects these biofilms and uses them to predict a person’s risk of developing cancer.  Such would be particularly helpful for the young.

Last updated: March 23, 2016 at 4:34 am for SEO optimization.

In health through awareness,

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3 thoughts on “Colon Cancer, Biofilm, Bacteria, Probiotics Role”

  1. [Bullman et al 2017] Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer, https://www.ncbi.nlm.nih.gov/pubmed/29170280

    Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome, including Bacteroides, Selenomonas and Prevotella species, is maintained in distal metastases, demonstrating microbiome stability between paired primary-metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.

  2. Microbiome and cancer. More reasons to fix your gut microbiome!

    How the Microbiome Can Affect Cancer, http://blog.aacr.org/how-the-microbiome-can-affect-cancer/#.WH-OIoUNRX0.linkedin

    Bacteroides fragilis as a particularly bad actor in the gut. This bacterium produces a toxin that damages normal intestinal cells, leading to a chronically inflamed intestinal microbiome prone to generate cancers. When Dr. Sears transferred the bacterium to mice inclined to develop benign intestinal polyps, the mice formed colorectal cancers instead.

    The paper, Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis, http://cancerres.aacrjournals.org/content/76/8/2115, April 2016 found that colorectal cancers associated with B. fragilis could be suppressed, not just by eradicating the microorganism, BUT ALSO BY REDUCING INFLAMMATION. ****This opens up new avenues for preventing colorectal cancers by altering the relationships between the microbiota and immune cells in the gut microbiome. Several other intestinal bacteria are also likely to affect colorectal cancer development. A gut microbiota rich in these pro-cancer bacteria may drive a microbiome toward chronic inflammation and cancer.****

    Will altering the microbiota and microbiome be a cornerstone of cancer prevention and treatment? Can so-called probiotics be developed and demonstrated to improve health? What is a healthy microbiome and how can it be maintained? Finding answers to these questions may go a long way toward preventing and treating human cancers.

    The influence of the intestinal microbiota on immune responses may even extend to how effectively the body’s immune system can be activated to fight cancers. Two recent reports in Science suggest that the presence of certain bacteria in the intestinal microbiome was accompanied by better anti-cancer responses to immunotherapy. The bacteria enhanced the effects of new immunotherapy drugs like Yervoy (ipilimumab), Opdivo (nivolumab), and Keytruda (pembrolizumab).

  3. Oxylipins produced by Pseudomonas aeruginosa promote biofilm formation and virulence, full text, Dec 2016, http://www.nature.com/articles/ncomms13823 ScienceDaily article, Researchers’ findings offer clue on how to block biofilm shields of bacterial infections, https://www.sciencedaily.com/releases/2016/12/161212152525.htm

    Bacteria Pseudomonas aeruginosa is an antibiotic resistant bacteria. “Oxylipins produced by P. aeruginosa promote biofilm formation and virulence. When P. aeruginosa produces oxylipins the biofilm is stronger.

    Oxylipins act to promote the organization of bacterial colonies into a more complex organization known as biofilm, where the bacteria are embedded inside a matrix that protect them from antibiotics.

    Their findings show that oxylipin production essentially changes the bacteria from a free-swimming state to what amounts to a fixed state, allowing for the formation of a colony.

    “We think oxylipins are signaling molecules that probably trigger other known or unknown pathways responsible for the biofilm production,” Campos-Gomez said.

    New meds/therapy of an oxylipin blocker could make a formerly antibiotic-resistant bacterial infection once again treatable.

    This was in vitro and in vivo (Drosophila flies) studies. They demonstrated that the oxylipins produced by the bacterium promoted virulence in the flies and in lettuce leaves.

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