Understanding spatial relations of gut bacteria in ulcerative colitis patients

To sample the microbial communities in the gut, fecal samples are generally collected from an individual and DNA is sequenced to identify bacteria that are present. This is an overall effective method, however, it does not provide information of the specific spatial location of bacteria within the gut. In a study published in the journal Gut, researchers in Ireland looked to determine differences in the bacterial composition of specific regions of the large intestine between patients with ulcerative colitis and control patients.

Four volunteers undergoing routine colonoscopies were recruited to serve as the controls for this study. Five patients with ulcerative colitis (UC), who were undergoing colectomies, or surgical removal of the colon, were also involved in the study. Samples were taken at four locations in the colon in all individuals: the caecum, traverse colon, descending colon, and rectum. The four locations were sampled three times at three different levels: luminal brush, whole mucosal biopsy, and laser captured sample of mucus gel layer. A total of twelve samples were taken per individual.

After analysis of the many samples it was discovered that there was more variability between the bacterial compositions between subjects than there was within the different locations of an individual’s colon. The findings showed a difference between the luminal and mucus gel microbiota in both the controls and the ulcerative colitis subjects. Three bacterial families were common between this difference shared by controls and UC subjects, namely Bifidobacteriaceae, Peptostreptococcaceae, and Enterobacteriaceae being more abundant in UC patients.

This study has its limitations because of the small sample size, however the researchers state that the small sample allowed for extensive analysis of the individual samples. So what do the findings of this study mean for patients with ulcerative colitis? Better understanding of differences in the spatial relations of bacteria could lead to the modulation of microbial communities to help treat ulcerative colitis. 

Gut microbiota reveal better ways of detecting (and preventing) colorectal cancer

Editors note:  The AMI is thrilled to have a guest blog post today from Kristina Campbell, a very talented science writer who specializes in the microbiome.  She writes for the Gut Microbiota for Health Experts Exchange, and blogs as The Intestinal Gardener.  Our readers can also keep up with her on Twitter,  @bykriscampbell.  

By Kristina Campbell

Scientists are starting to develop an idea of how colorectal carcinoma (CRC) arises. It all starts with bacteria in the digestive tract: possibly a strain of Bacteroides fragilis or the infamous Escherichia coli. Whether the bacteria are new to the body, or resided there all along, doesn't matter. The bacteria somehow get a green light to start producing chemical agents that damage the genetic information in the body's cells. The damaged cells rapidly divide. Soon enough, polyps (also called adenomas) appear in the colon. These polyps can become cancerous.

Currently, there's a gap in CRC detection methods. This is a problem that's directly connected with patient mortality: if CRC is detected at an early stage, survival rate is more than 80%. But if it's left until a late stage, it's less than 10%.

The two standard ways to detect this cancer are a fecal occult blood test (FOBT) and a colonoscopy. FOBT – which tests for traces of blood in the stool – has limited sensitivity for CRC. It's only a rough guide, since it misses many cases. Colonoscopy is the most effective method of diagnosis, but it's far from perfect because it's invasive and costly.

New research shows that the microbiota might lead to better CRC detection. Iradj Sobhani and colleagues recently published an intriguing paper in Molecular Systems Biology called ‘Potential of fecal microbiota for early-stage detection of colorectal carcinoma'. They took fecal samples from healthy people and those with confirmed CRC, and used metagenomic sequencing to find out how they differed.

They found that the fecal samples held clues that were missing from FOBT. Using both methods together, they increased the sensitivity of colon cancer detection 45% (as compared with FOBT alone). Used effectively in the clinic, this could save thousands of lives each year.

Sobhani said he and his colleagues are working on a clinical tool to help patients make use of this information. In a recent interview, he said, "Now we know a panel of some 18-20 [relevant] bacteria and we are trying to make an easy and simple tool to identify these bacteria. We can, I hope, in a very short future time, make low-cost tools to identify the bacterial phenotype usually found in patients with colon cancer."

A smaller study from the Schloss lab found a similar result: enhanced CRC detection using information from FOBT and a fecal sample, as well as body mass index, age, and race (which are known risk factors for colon cancer).

Schloss said that one kind of bacteria in particular piqued his interest. "We’re trying to better understand [why] Fusobacterium seems to be popping up in a lot of these stories. How does Fusobacterium get from the mouth to the gut? Everybody has it in their mouth. But not everybody has it in the gut. So what’s breaking down there? Does it have a role in disease?"

The Sobhani study went beyond CRC detection to factors that might be involved in prevention. The researchers looked at the bacterial genes in the guts of those with CRC and asked, "What can these bacteria do well?" In other words, they looked at the bacterial functions as indicated by their genes.

This analysis showed some interesting links to diet. Sobhani explained, "Those with colon cancer had largely more meat-metabolizing bacteria] compared to those who have no colon cancer, who have bacteria that show more functions to metabolize vegetables." He added, "Then there are functions involved in the transfer and capture of… minerals."

Whatever made the meat metabolizers more abundant in the colon could turn out to be what caused the cancer in the first place. But it's not clear whether red meat consumption itself accounts for the disease-associated condition of the microbiota, or whether other components of the diet play a role. (Fiber is a prime preventative candidate under investigation.)

A whopping 95% of CRC could be attributable to environmental factors. More research related to the gut microbiota and CRC might one day reveal exactly what those environmental factors are, so we can kick colon cancer to the curb.

References:

Zackular J, Rogers M, Ruffin M and Schloss P. (2014) The Human Gut Microbiome as a Screening Tool for Colorectal Cancer. Cancer Prevention Research doi: 10.1158/1940-6207.CAPR-14-0129

Zeller G, Tap J, Voigt AY, et al. (2014) Potential of fecal microbiota for early-stage detection of colorectal cancer. Molecular Systems Biology doi: 10.15252/msb.20145645

The effects of bowel cleansing for colonoscopies on our microbiome

Colonoscopies and colonic surgeries are known to require bowel cleansing prior to the procedure.  To accomplish this, what are thought to be generally safe and effective products are used in order to cleanse the bowel. One commonly used cleanser is polyethylene glycol (PEG) supplemented with electrolytes. While the efficiency of this product has been tested, limited data has been collected on its effects on the microbiome of the colon.

A new study published on January 6th in the journal Gut tested the effects of bowel cleansing on the bacteria that colonize an individual’s gastrointestinal tract. 23 human subjects were put into two study groups, one group consuming the PEG electrolyte solution in a single dose of 2 L and the other group consuming the solution in two doses of 1 L.

They found that bowel cleansing had little long-term effect on an individual’s colonic microbiota though a substantial change was initially seen after consumption. In subjects who consumed the PEG electrolyte solution in two 1 L doses, the microbiota recovered to original composition after two weeks. In subjects who consumed the solution in a single 2 L dose, however, it took up to one month after treatment for the colonic microbiome composition to recover.

Due to these findings, the authors suggest that separating the dosage into two 1 L doses may benefit the microbiome of the patient and may be preferred in clinical practice. There are several new microbiome studies such as this one that could impact medical practice and it will be exciting to see how (and if) the outcomes outlined in these papers are adopted by clinicians into practice.