The gut microbiome might one day help prevent and treat colorectal cancer, according to researchers at Baylor College of Medicine, Texas Children’s Hospital and Columbia University. In a study that appeared in the American Journal of Pathology, the team of researchers reports that administration of histamine-generating gut microbes reduced inflammation and tumor formation in mice that lacked that ability to produce histamine on their own. These results suggest that alteration of the gut microbiome with probiotics may become a new preventative or therapeutic strategy for patients at risk for colorectal cancer associated with inflammatory bowel disease.

“We are on the cusp of harnessing advances in microbiome science – the study of the microbes living in our body – that would facilitate diagnosis and treatment of human disease,” explained Dr. James Versalovic, Milton J. Finegold Professor of Pathology & Immunology at Baylor College of Medicine and pathologist-in-chief at Texas Children’s Hospital. “By simply applying diet-based cancer prevention strategies, such as supplementing microbes that provide missing life substances, we can potentially reduce the risk of cancer.”

Previous studies had shown that histamine, a chemical produced by the body that is well-known for its role in allergic disease, also may have a potential antitumor effect. In this study, the researchers investigated whether the probiotic L. reuteri 6475, which is able to generate histamine, had the ability to reduce the frequency and severity of inflammation-associated colorectal cancer in mice that were not able to produce histamine on their own.

The researchers conducted a series of experiments using mice that were deficient in histidine decarboxylase, the enzyme required to convert L-histidine to histamine. Experimental mice were orally administered L. reuteri 6475, which has the gene for histidine decarboxylase to produce histamine; control animals received L. reuteri that lacked the gene to produce histidine decarboxylase. The probiotic was administered both before and after the mice received a single treatment to induce tumor formation. Fifteen weeks later, the mice were sacrificed and the tissues removed for study.

The animals treated with L. reuteri 6475 showed increased expression of bacterial histidine decarboxylase enzyme and of the amount of histamine in their colons. Positron emission tomography (PET) used to visualize the tumors showed that these mice had fewer and smaller tumors than control mice. L reuteri strains deficient in histidine decarboxylase activity did not provide protective effects; the mice showed increased numbers of “hot spots” indicative of tumor formation.

Treatment with the histamine-generating probiotic also reduced inflammatory responses typically associated with increased risk of tumor development. According to Versalovic, “These observations are consistent with the conclusion that histamine-generating probiotic L. reuteri may attenuate development of colorectal cancer in the animal model, at least in part, via reduction of a pro-cancer inflammatory response.”

The role of histamine in human cancer is still unclear. However, when investigators analyzed data obtained from 2,113 colorectal cancer patient samples taken from 15 datasets, results showed better survival in patients with elevated patterns of histidine decarboxylase. These findings indicate that histamine-generating probiotics, in the presence of sufficient histamine precursor L-histidine, may improve outcomes for patients with sporadic- and bowel disease-associated colorectal cancer.

“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 can promote human health and prevent disease,” Versalovic said.