New research on probiotics in the prevention and treatment of colon cancer

September 13, 2017, Elsevier
Figure shows presence of colonic tumors (MRS/AOM+DSS panel) by positron emission tomography imaging. Tumor activity is significantly diminished in the presence of the histamine-producing probiotic (L. reuteri 6475/AOM+DSS). Credit: The American Journal of Pathology

In an innovative approach to colorectal cancer (CRC) prevention and treatment, scientists are studying ways to replace missing metabolites in patients prone to gut inflammation and CRC. A new study in The American Journal of Pathology describes how administration of histamine-producing gut microbes to mice lacking the enzyme histidine decarboxylase (HDC) reduced inflammation and tumor formation. These results suggest that alteration of the gut microbiome with probiotics may become a new preventative or therapeutic strategy for patients at risk for inflammatory bowel disease (IBD)-associated CRC.

"We are on the cusp of harnessing advances in microbiome science to facilitate diagnosis and treatment of human disease," explained James Versalovic, MD, PhD, pathologist-in-chief at Texas Children's Hospital, and Milton J. Finegold Professor of pathology & immunology at Baylor College of Medicine (Houston). "By simply introducing microbes that provide missing life substances, we can reduce the risk of cancer and supplement diet-based cancer prevention strategies."

Researchers conducted a series of experiments using that were deficient in HDC, the enzyme required to convert histidine to histamine. Experimental mice were orally administered the probiotic Lactobacillus reuteri 6475, which is known to possess the histidine decarboxylase gene (hdc+) and is able to convert histidine to histamine; control animals received a placebo. The probiotic was administered both before and after the mice received a single dose of a colonic carcinogen (azoxymethane) plus an inflammation-inducing chemical (DSS) to induce tumor formation. Fifteen weeks later, the mice were sacrificed and the tissues removed for study.

The probiotic increased expression of bacterial HDC and amounts of histamine in the colons of the mice. Using positron emission tomography (PET) to visualize the tumors, control-treated mice showed evidence of tumors and increased glucose uptake in colon walls. In contrast, mice administered the probiotic had fewer and smaller tumors and significantly diminished areas of glucose uptake.

Inactive L. reuteri strains (those deficient in HDC activity) did not provide protective effects. These mice showed increased numbers of "hot spots" indicative of and increased abdominal .

The active probiotic also reduced inflammation induced by the carcinogen plus DSS, as indicated by suppressed pro-inflammatory cytokine gene expression (i.e., those encoding KC, interleukin (IL)-22, IL-6, tumor necrosis factor (TNF), and IL-1α) and reduced cytokine concentrations in plasma (i.e., KC, IL-22, and IL-6). The active probiotic also counteracted an increase in immature myeloid cells induced by the carcinogen. According to Dr. Versalovic, "These observations are consistent with the conclusion that histamine-generating probiotic L. reuteri may attenuate AOM+DSS-induced colon carcinogenesis, at least in part, via enhanced maturation of circulating myeloid cells and concomitant reduction of pro-inflammatory cytokines."

The role of histamine in human cancer is still unclear. However, when investigators analyzed data obtained from 2,113 CRC patient samples taken from 15 datasets, results showed better survival in patients with elevated patterns of HDC and histamine receptor gene expression. These findings indicate that histamine-generating probiotics, in the presence of sufficient protein (L-histidine) intake, may improve outcomes for patients with sporadic and IBD-associated CRC.

"Our results suggest a significant role for histamine in the suppression of chronic intestinal inflammation and colorectal tumorigenesis. We have also shown that cells, both microbial and mammalian, can share metabolites or chemical compounds that together promote human health and prevent disease," said Dr. Versalovic.

Explore further: Tourette-like tics vanish in mice treated with histamine

More information: "Gut Microbe-mediated Suppression of Inflammation-associated Colon Carcinogenesis by Luminal Histamine Production," American Journal of Pathology (2017). DOI: 10.1016/j.ajpath.2017.06.011

Related Stories

Tourette-like tics vanish in mice treated with histamine

June 6, 2017
Yale scientists produced increased grooming behavior in mice that may model tics in Tourette syndrome and discovered these behaviors vanish when histamine—a neurotransmitter most commonly associated with allergies—is ...

Gut microbes may promote immune responses against colorectal cancer

September 6, 2017
Bacteria in the gut could stimulate tumor cells to produce factors that regulate cell mobility called chemokines that recruit T cells to the tumor, which is linked to improved outcomes, according to data presented at the ...

Gut bacteria may hold key to treating autoimmune disease

December 19, 2016
Defects in the body's regulatory T cells (T reg cells) cause inflammation and autoimmune disease by altering the type of bacteria living in the gut, researchers from The University of Texas Health Science Center at Houston ...

Chronic liver inflammation linked to Western diet

July 12, 2017
A new study in The American Journal of Pathology reports that mice fed a Western diet, which is high in fat and sugar, resulted in hepatic inflammation, especially in males. Moreover, liver inflammation was most pronounced ...

Exposure to common environmental bacteria may be source of some allergic inflammation

January 31, 2012
Could some cases of asthma actually be caused by an allergic reaction to a common environmental bacteria? New research findings published in the Journal of Leukocyte Biology suggests that this idea may not be as far-fetched ...

Microbes in the gut help determine risk of tumors

November 5, 2013
Transferring the gut microbes from a mouse with colon tumors to germ-free mice makes those mice prone to getting tumors as well, according to the results of a study published in mBio, the online open-access journal of the ...

Recommended for you

Metastatic lymph nodes can be the source of distant metastases in mouse models of cancer

March 22, 2018
A study by Massachusetts General Hospital (MGH) investigators finds that, in mouse models, cancer cells from metastatic lymph nodes can escape into the circulation by invading nodal blood vessels, leading to the development ...

Could a pap test spot more than just cervical cancer?

March 22, 2018
Pap tests have helped drive down rates of cervical cancer, and a new study suggests they also could be used to detect other gynecologic cancers early.

Researchers examine role of fluid flow in ovarian cancer progression

March 22, 2018
New research from Virginia Tech is moving physicians closer to pinpointing a predictor of ovarian cancer, which could lead to earlier diagnosis of what is know as the "silent killer."

Probing RNA epigenetics and chromatin structures to predict drug resistance in leukemia

March 22, 2018
Drug resistance is a major obstacle to effective treatment for patients with cancer and leukemia. Epigenetic modifying drugs have been proven effective for some patients with hematologic malignancies, such as myelodysplastic ...

Researchers identify compound to prevent breast cancer cells from activating in brain

March 22, 2018
Researchers at Houston Methodist used computer modeling to find an existing investigational drug compound for leukemia patients to treat triple negative breast cancer once it spreads to the brain.

Gene-based test for urine detects, monitors bladder cancer

March 22, 2018
Researchers at The Johns Hopkins Kimmel Cancer Center have developed a test for urine, gathered during a routine procedure, to detect DNA mutations identified with urothelial cancers.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.