Microbiome differences between healthy people and those with IBS

Methane (above) is produced by Methanogens, which are increased in the guts of healthy individuals compared to those with diarrheal IBS.

IBS affects somewhere around 11% of all humans.  It is not known exactly what causes the disease but it is characterized by a low grade inflammation in the colon which can manifest itself as cramping, bloating, diarrhea, constipation, and overall abdominal discomfort.  Many scientists now believe this is a microbiome mediated disease that is caused by some sort of dysbiosis in the gut, unfortunately efforts to characterize exactly what differences occur in IBS individuals have not been successful.  A new article published last week in Nature Scientific Reports describes newly discovered differences in butyrate and methane producing bacteria in the guts of people with IBS.

The scientists sequenced the microbiomes of 66 healthy controls and 113 folks with IBS, at two time points 1 month apart.  They discovered that IBS patients had higher amounts of Bacteroides and lower levels of Firmicutes than healthy individuals, as well as an overall lower microbiome diversity.  In addition, there were no major changes to either group’s microbiomes over the one month measurement window.  Interestingly those people with diarrheal IBS had much lower levels of methanogens than healthy controls, and those people with constipation IBS had higher levels of methanogens than healthy controls.  Methanogens convert hydrogen gas to methane in the gut, and this study revealed a link between methane production and gastrointestinal (GI) transit time.  Finally, the researchers determined that diarrheal IBS patients also had much lower levels of known butyrate producers.  Butyrate, a short chained fatty acid (SCFA), is associated with improved GI permeability and overall GI health.

This study described a few important insights in IBS and the microbiome.  These insights, such as the metabolic differences between bacteria in healthy individuals and those with IBS may be important to future therapeutics to treat this disease.  For example, perhaps folks with IBS could eat a lot of fiber and in the hopes of increasing the amount of butyrate in their guts.  Of course, the observed difference is only an association at this point, but other studies have suggested an increase in fiber can help relieve symptoms of the disease. 

Stool consistency should be considered during microbiome research

Stool sampling remains the most common method of measuring the microbiome of the GI tract.  Researchers are well aware of its limitations, but its ease and convenience for both scientists and donors makes it nearly irreplaceable at the moment.  The most common issue regarding stool samples that is often pointed out is that it is not representative of the GI tract, and that it only samples the lower colon and not the more proximal GI tract.  In addition, it does not account for bugs that are attached to the mucous linings of the intestine rather than those that transiently pass with our feces.  Related to this point, last week Jack Gilbert and John Alverdy, professors from the University of Chicago, published a piece in the journal Gut regarding stool microbiome sampling and stool consistency.

Professors Gilbert and Alverdy argue that stool consistency greatly affects the stool microbiome populations.  The stool consistency is normally a function of intestinal transit time, with the shorter the duration between eating and passing stool being associated with watery stool, while a longer duration is associated with a more solid stool.  They point to studies that that show different bacteria have evolved to either grow rapidly when the stool is quickly moving through the lumen, in order to proliferate with the shorter duration access to nutrients, or to grow slowly and more completely utilize the available nutrients when the stool is accessible for longer periods.  Measurements of stool consistency are hardly ever performed during normal sampling, and these same studies tend to make generalizations about different phyla, like Bacteroides and Ruminococcacea, when in fact these different can be explained by stool consistency. 

In a time where microbiome diagnostics are starting to be considered as helpful indications for varous diseases, this type of quality control needs to be established.  Stool sampling is not perfect, but it is necessary, and for that reason steps should be taken now to improve and control its usefulness, especially in a clinical setting. 

How does the gut microbiome recover after diarrhea?

Scanning electron microscope image of Vibrio cholerae, the cause of cholera and a major cause of diarrhea-associated deaths each year.

Diarrhea is an important global health challenge that kills nearly two million people each year.  Even when it is not lethal it can have important detrimental impacts, especially on children.  For example, frequent diarrhea is associated with decreases in height, IQ, and heart health.  Diarrhea is frequently a microbiome – based disorder, and gut pathogens like enterotoxin producing Escherichia coli and Vibrio cholerae are often the culprits.  Using diarrhea caused by these pathogens as their model, scientists from Harvard University recently studied how the gut microbiome rebounds after diarrhea.  They published their results in Mbio.

The scientists measured the stools of 41 people (both children and adults) in Bangladesh that had diarrhea caused by E. coli or V. cholerae (the cause of cholera).  They measured the patients’ stools before, during, and after their diarrhea episodes and tracked the changes that occurred in all patients’ stools.  Interestingly, they identified a consistent succession of the gut microbiome that occurred in nearly all cases, regardless of the cause of diarrhea.  First, the diarrhea (or antibiotic treatment for the diarrhea) clears out much of the microbiome, and leaves both carbohydrates and oxygen to accumulate in the gut.  (Carbohydrates and oxygen would normally be metabolized by the microbiome, but in the absence of many bacteria, these things accumulate.)  Next, oxygen respiring and carbohydrate utilizing bacteria (especially those using simple carbs) colonize the gut and decrease the abundance of both of these substrates.  After, the lack of simple sugars and oxygen leads to a decline in the population of bacteria that use these, and the succession to anaerobic (i.e. do not respire oxygen), complex carb fermenting bacteria begins.  Finally, the gut microbiome resembles the complex community that existed prior to infection and the onset of diarrhea.  The entire process takes about 30 days to complete, but depends on a variety of factors such as diet, antibiotic use, and duration of diarrhea.

Studies like this one are important to combatting diarrhea, and shortening recovery time.  For example, it is now known that oxygen accumulates after diarrhea, and that while it exists at high levels the microbiome is not fully recovered.  Perhaps introducing an agent after diarrhea that rapidly decreases the amount of oxygen in the terminal gut could hasten the microbiome recovery time and improve the patient’s wellbeing.  Next time you have diarrhea, remember that it takes almost a month for your microbiome to recover, so nurture during that time.