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. 

Sex, body mass index, and dietary fiber correlated with microbiome composition

On last week’s podcast, we talked with Erica and Justin Sonnenburg about how the food we eat, and specifically dietary fiber, is important for “feeding” our microbiomes. All of the variables that influence microbiome composition are not fully understood, however research is continually being conducted to better understand what factors affect the microbiome.  To this end, a team of scientists from New York University School of Medicine set out to find how sex, body mass index (BMI), and dietary fiber intake impact the microbiome.

The scientists analyzed fecal samples from 82 individuals, 51 men and 31 women. They found that the women had different microbiome composition than the men, specifically a lower abundance of Bacteroidetes. They also found that BMI impacted microbiome diversity, specifically in women. Overweight and obese women had less diverse gut bacteria than normal weight women and women with a higher BMI also had less Bacteroidetes in their guts compared to the normal weight women.

The scientists also found that various sources of dietary fiber differentially impacted the microbiome of subjects.  Fiber intake from fruits and vegetables resulted in higher levels of Clostridia and fiber intake from beans was associated with greater abundance of Actinobacteria. It is possible that dietary fiber is influencing the microbiome by reducing gut transit time and lowering the pH. It is also possible that it is influencing systemic levels of estrogen, which could alter microbiome composition.

As the microbiome continues to be implicated in diseases, the ability to identify variables that affect the microbiome are important and can potentially be used for altering microbiota composition to prevent or possibly treat disease. 

Gut bacteria help regulate serotonin levels

Ball-and-stick model of serotonin molecule

Editor’s Note:  In this blog we write about the most recent findings from Elaine Hsiao’s lab at Cal Tech.  You may remember Professor Hsiao’s previous work, which we wrote about last year.  She published the now seminal article that linked autism spectrum symptoms in mice with their gut microbiomes.  Diane will be joining us on the Microbiome Podcast, to be released on May 4.  If you have any questions about this study on serotonin, or on her work with autism and the microbiome, please call this number 518-945-8583 and leave a voicemail.  If possible we will ask her your question during the show.

Serotonin is a crucial multi-purpose hormone in our body that affects our mood, happiness, appetite, and gastrointestinal movement, among other functions.  It is produced in a few places around the body, but mostly in the epithelial cells that line the gut.  It should come as no surprise then, that Professor Diane Hsiao’s group, out of Cal Tech, recently uncovered a critical role that the gut microbiome has in stimulating the production of this molecule.  She published her results in the journal Cell.

The researchers first discovered that germ-free mice produced substantially less serotonin than normal mice in their colons, but not in the small intestines, suggesting the importance of the colon microbiome in serotonin production.  The scientists then investigated the levels of each enzyme responsible for serotonin production and pinpointed one called TPH1 that was produced at much lower levels in the germ free mice colons.  When the germ-free mice were given TPH1 their serotonin levels returned to normal, and when regular mice were given antibiotics their serotonin levels dropped.  Taken together, this suggests that the colon microbiome somehow increase TPH1 levels in the gut.   

The researchers then investigated the effects that specific bacteria had on increasing serotonin levels in germ free mice and discovered that spore forming bacteria, especially those belonging to Clostridia, were able to increase the levels of serotonin in the mice.  After, they tried to determine specific metabolites that may be produced by Clostridia that increase TPH1 production.  They found that deoxycholate, a-tocopherol, p-aminobenzoate, and tyramine all increased serotonin to normal levels when given to germ free mice.

Finally, the scientists colonized germ-free mice with spore producing bacteria and measured the effects on certain traits known to be associated with serotonin.  For example, germ free mice colonized with spore producing bacteria had longer food transit times and more frequent bowel movements.  In addition, blood platelets function better in mice colonized with spore forming bacteria than in germ-free mice.

Overall this work shows an important connection between serotonin production and the microbiome.  Serotonin has been implicated with many critical bodily functions, like bone development, appetite control, heart function, and mental well-being.  The fact that a dysbiosis in the microbiome may be responsible for lowering its levels may turn out to be crucial in developing next generation therapeutics.