Intestinal microbiota in patients with colon cancer is altered by probiotic intervention
Intestinal microbiota in patients with colon cancer is altered by probiotic intervention
Summary of the study and findings
A clinical study was conducted by the Sahlgrenska Academy at University of Gothenburg, Sweden to find out whether the use of probiotics can alter the composition of intestinal bacteria in humans with colon cancer. Previous studies have demonstrated beneficial effects of probiotic bacteria in reducing mucosal inflammation and colon tumour development in animals, but supporting clinica data in humans were limited. The Swedish study involved 15 patients with colon cancer at Sahlgrenska University Hospital. Eight of them were given two tablets a day of ProBion Clinica, the brand chosen as the beneficial probiotics for the study. The other 7 colon cancer patients, together with another 21 non-cancer patients served as the control group and were given no probiotic intervention.
Comparing tumor, mucosal and fecal samples, it was found that the cancer patients who took probiotics had their microbiota significantly altered compared with those who did not take probiotics. In these patients, cancer-associated harmful bacteria were significantly reduced, replaced by an abundance of butyrate-producing beneficial bacteria. The result shows great promise for probiotics to play a role, upon further research, in the prevention or treatment of colon cancer. It also shows that ProBion Clinica tablets produce adequate quantities of live bacteria that can safely pass through the gastrointestinal tract and deliver measurable probiotic performance in the large intestines.
The full study was published in BMJ Open Gastroenterology in July 2017. The study was approved by the Regional Ethical Review Board in Gothenburg and registered at ClinicalTrials.gov (ID: NCT03072641), with informed consent obtained from all study subjects.
Details of the Clinical Study
What is already known about colon cancer?
Colon cancer currently affects 1.4 million people a year and its incidence is increasing worldwide, with high motality rate.
Colon cancer patients have altered intestinal bacterial composition, with a proliferation of bacteria that thrive in an inflammatory, cancer-related micro-environment.
Previous research has found that certain cancer-associated bacteria can potentially serve as biomarkers for colon cancer.
Previous studies have demonstrated beneficial effects of probiotic bacteria in reducing colon tumour development and mucosal inflammation in animal models, but supporting clinical data in humans are limited.
What are the new findings?
Compared with non-cancer controls, colon cancer patients had a proliferation of harmful bacteria including oral-associated pathogens.
The bacteria species Peptostreptococcus was over-represented in both mucosal and faecal samples of colon-cancer patients and shows promises as a colon cancer biomarker.
The colon cancer-associated bacterial profile was significantly altered by probiotic intervenion. After intervention, it was characterised by a reduction of Peptostreptococcus and Fusobacterium and an enrichment of butyrate-producing bacteria.
What are Probiotics?
Probiotics are defined as live micro-organisms that, when administered in adequate amounts, confer a health benefit on the host.
What are the ProBiotic Strains used in this clinical study?
The bacterial strains used in this study, Lactobacillus acidophilius NCFM and Bifidobacterium animalis subsp. lactis BI-04, have a long history of safe use as commercial probiotics and documented health benefits. NCFM has shown efficacy for colonic tumour growth attenuation in rodents and was associated with reduced levels of procarcinogenic metabolites in the human gut. BI-04 has anti-inflammatory properties and was shown to alleviate colitis in mouse models.
What are the advantages of using ProBion tablets?
As this study aimed to show the effect of probiotics in altering bacterial composition in the gut where malignant tumour was present, it is paramount that the probiotics used can reach the large intestines and deliver performance. ProBion tablets fit the bill because the embedded bacteria have exceptional survivability in the gastrointestinal tract, and the 150-180 min slow release profile of the tablets ensures maximum deposition and activation in the large intestines. Flow cytometry analyses show that on average 85% of ProBion bacteria are live cells with undamaged cell membranes.
How was this study done?
This study had the participation of 15 adult patients who were diagnosed with stage 1-3 colon cancer, as well as 21 adult patients who were the non-cancer controls.
The 15 cancer patients had to fulfill the prerequisites of a) having at least one malignant tumour in the colon; b) did not recently take antibiotics; and c) did not consume probiotics regularly. Amongst this group, 8 of the patients were randomised to receive two ProBion Clinica tablets a day starting from their second visit to the clinic after colonoscopy, and ending on the day of their surgery (average length of taking probiotics was 31 days, the range being 8-78 days). The 7 patients who did not receive any probiotics acted as the control group in this part of the study.
The 21 non-cancer subjects served as controls for comparing the intestinal bacterial profile of subjects with colon cancer, and those without any cancer. Researchers wanted to see if patients with colon cancer harboured any distinct microbiota signature in their tumour tissue and nearby mucosa.
Although the non-cancer control subjects did not have any tumours, they were in hospital to undergo colonoscopy because they had abdominal symptoms such as diarrhoea, constipation, abdominal pain, lower gastrointestinal bleeding or iron-deficient anemia. The prerequisites for inclusion into the control group were a normal-appearing colonic mucosa. Any subjects with pathology such as colonic polyps, inflammatory bowel disease and colitis were excluded.
At the beginning of the study, tissue samples were obtained using regular biopsy forceps from the colon all the 36 subjects who underwent colonoscopy. Faecal samples were also obtained post-colonoscopy. Analyses of these samples provided baseline data showing the intestinal microbacterial profile of the cancer group and the control group.
Thereafter patients with colon cancer were randomised to receive, or not receive probiotics for a period of time before they underwent surgery. At surgery, biopsies from tumour tissue and nearby mucosal tissues were obtained as well as faecal samples. These samples were then analyzed to see if there were any differences between those subjects who took probiotics and those who did not.
Result - Probiotic intervention makes a difference!
First, by comparing baseline data, it was found that colon cancer patients did harbour a distinct microbial signature - in this case characterised by a proliferation of bacteria including Fusobacterium and Peptostreptococcus, two species not present in any significant amounts in control subjects.
For the patients who took probiotics, it was found that their levels of Fusobacterium and Peptostreptococcus - two species proposed as colon cancer biomarkers - were greatly reduced in the faecal samples. On the other hand, an abundance of butyrate-producing bacteria showed up in their tumour, mucosa and faecal samples. Butyrate plays a beneficial role in colon cancer by inhibiting cell proliferation, reducing inflammation and promoting cell apoptosis and tumour suppresor gene expression. This means that probiotic intervention had a positive value in enhancing the gut bacteria composition for colon cancer patients. The result also shows that ProBion Clinica tablets were able to fulfill their function as a viable agent for probiotic intervention.
It is not clear whether dysbiosis (excess of harmful bacterial over beneficial bacteria) in the gut promotes carcinogenesis (cancer development), or possibly the tumour micro-environment and related inflammatory state cause microbial dysbiosis. But what is clear is that a distinct microbial profile exists in the colonic tumour and the nearby mucosa tissues. This profile is characterised by the proliferation of certain bacterial groups and the depletion of other groups.
The results of this study support the hypothesis that colon cancer-associated microbiota can be manipulated by specific probiotic strains, resulting in an altered microbiota enriched with beneficial bacteria. The study provides evidence that microbiota modulation by probiotics could be considered as part of a therapeutic regime for colon cancer patients.
Further studies should be conducted to confirm these initial findings and ascertain how probiotics can be used to influence the development and progression of carcinogenesis. The probiotic strains used in this study, Lactobacillus acidophilius NCFM and Bifidobacterium animalis subsp. lactis BI-04, show promise as a beneficial component of treatment and therapeutic development in colon cancer.