Probiotics May Help Prevent, Treat Colorectal Cancer

Introducing microbes to replace missing metabolites could reduce cancer risk, study suggests.

Using probiotics to alter the gut microbiome could one day serve as a preventative and therapeutic strategy for patients at risk of inflammatory bowel disease (IBD)-associated colorectal cancer, new findings suggest.

For the study, investigators used mice with a histidine decarboxylase (HDC) deficiency, which is an enzyme needed to convert histidine to histamine.

The experimental mice were administered the probiotic Lactobacillus reuteri 6475 orally, whereas the controls received a placebo. L reuteri was administered before and after the mice received a single dose of azoxymethane plus an inflammation-inducing chemical (DSS) to induce tumor formation.

After 15 weeks, the mice were humanely killed and the tissues were removed for observation.

The results of the study, published in the American Journal of Pathology, showed the probiotic increased HDC expression and the amount of histamine in the colons of the mice.

Positron emission tomography was used to visualize the tumors, showing that the mice in the control group had tumors and an increase of glucose uptake in the colon walls. Contrastingly, mice in the probiotic arm had both fewer and smaller tumors with significantly diminished areas of glucose uptake.

The authors noted that inactive L reuteri strains did not provide any protective effects, rather the mice showed increased numbers of so-called hot spots indicating tumor formation and increased abdominal glucose uptake.

The active probiotic reduced inflammation caused by the carcinogen plus DSS and reduced cytokine concentrations in plasma. Additionally, it counteracted an increase in immature myeloid cells induced by the carcinogen.

“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,” said author James Versalovic, MD, PhD, pathologist-in-chief at Texas Children’s Hospital.

Although the role histamine plays in cancer remains unclear, when the investigators analyzed data from 2113 colorectal cancer patient samples obtained from 15 data sets, they found that patient survival was better in individuals with elevated patterns of HDC and histamine receptor expression.

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

Dr Versalovic noted, “We are on the cusp of harnessing advanced in microbiome science to facilitate diagnosis and treatment of human disease. By simply introducing microbes that provide missing life substances, we can reduce the risk of cancer and supplement diet-based cancer prevention strategies.”