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. 

Human genetics, the microbiome, and obesity

Editors note: Happy birthday to our intern, Becky Siegert.  She has been helping to bring you the blogs for the past 3 weeks, and we at the AMI deeply appreciate her help with them.  Enjoy the day, Becky!

An article was published last week in Cell out of Ruth Ley's lab at Cornell University that discovered a connection between host genetics and the microbiome.  In doing so, the researchers discovered which aspects of the microbiome were heritable, and how some heritable bacteria in the microbiome are related to obesity.

The researchers obtained stool samples from almost a thousand humans that were twins.  They discovered that twins had more similar microbiomes than non related individuals, and that identical twins had even more similar microbiomes than fraternal twins.  Then, by meticulously analyzing their data sets along with other published twins data they discovered which specific types of bacteria were the most heritable.  They discovered that the bacteria from the family Christensenellaceae were the most heritable.  Interestingly, this family seems to exert great influence over the existence or non existence of other important bacteria in the gut, and it often occurs with methane producing archaea.  Additionally, this family of bacteria appeared to be associated with a low body mass index (BMI), or leanness.  To test the effect of this family of bacteria on obesity the researchers performed a series of microbiome transplants from humans to germ free mice.  In one test, an obese microbiome that was amended with a Christensenellaceae bacteria prior to transplantation resulted in weight loss for the mouse.  In other tests the amount of weight gain in mice mirrored the amount of Christensenellaceae.

This study is important in many ways.  First, it unambiguously connects host genetics to the microbiome.  Second, it connects a specific family of bacteria, Christensenellaceae, to BMI.  This family is heritable and seems to play a large role in shaping the rest of the microbiome.  Altogether this paper adds a new dimension to the microbiome and nutrition.  Many studies associate certain genes with obesity, but perhaps the microbiome is actually responsible.