Bile Acids, Inflammatory Bowel Disease, and the Microbiome: A Rapidly Developing Story

Back in January, I wrote about how bile acids are regulators of inflammation and thus, when dysregulated (either too high or too low), this dysregulation can lead to disease.  Bile is produced by the liver and excreted into the intestines to digest fat.  Gut bacteria convert these primary bile acids into secondary bile acids, which are, in turn, immune signaling molecules, and I described research out of Harvard looking at the exact mechanism of action.  In that post, I also wrote about a second paper, also from Harvard, that looked at how diet and the gut bacteria work together to modify these immune-mediating bile acids.  I mention that “…low levels of bile acids make the mice prone to developing inflammatory conditions, like IBD.”

Well, new research out of Stamford University has zeroed in on a particular kind of bacteria missing from those with ulcerative colitis (UC) which may be responsible for the development of the disease.[i]  The study consisted of 2 groups of patients, 17 with UC who had undergone surgery to remove the colon and rectum.  The surgeons then reposition the lower end of the small intestine to create a pouch that acts as a rectum. Unfortunately, half of these UC patients develop a condition called pouchitis, which is inflammation of this pouch similar to the UC itself.  The second group of patients had a rare genetic condition which leads to that same surgery but almost  never develop pouchitis.  In comparing the two groups, they noted that those with UC had markedly lower levels of  both microbial diversity and secondary bile acids, including the two most prominent, deoxycholic acid and lithocholic acid, mirroring the Harvard research.  They noted too that the family of bacteria called Ruminoccoccaceae was significantly low in the UC patients versus the others.  These bacteria, along with several other kinds, carry the genes to create secondary bile acids.  Ruminococcaceae are a family of bacteria within the class of Clostridia.[ii]

In fact, when primary bile acids were incubated in stool samples from the patients with the genetic condition, secondary bile acids were created.  This did not happen with the same procedure using stool samples from the UC patients.  And in 3 different animal studies, when mice with IBD were supplemented with these 2 bile acids, markers for inflammation  markedly improved.

There is a phase 2 clinical trial happening at Stamford right now on 15 patients with UC who have had this pouch surgery; they are being given a naturally occurring secondary bile acid which is already approved by the FDA for other conditions.  I will absolutely keep an eye out for those results.  However, looking at Clinical Trials.gov, it looks like the primary completion date of the study isn’t until December 2025.  (I wish that there were a trial ongoing for those who have not as yet lost the bottom of their colon/rectum.  It would be great to see if this treatment could help prevent that horrible surgery in the first place.)

A postscript:  as I was getting ready to post this, I spotted breaking news about a brand new study out of Michigan State University about the discovery of brand new bile acids that are produced only by our gut microbes, not by our own bodies.[iii]  The discovery has apparently rocked the scientific world in that, no new bile acids have been found since their initial discovery in 1848:  “This discovery will change how medical textbooks address digestion, and it contributes to an ever-growing body of knowledge supporting the importance of the microbiome…”  And these new bile acids are “…particularly abundant in the guts of people suffering with gastrointestinal diseases, such as Crohn’s…”

This is really a developing story: the recognition of a completely altered bile acid composition in those with diseases involving intestinal inflammation.  Definitely stay tuned!

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[i] Sidhartha R. Sinha, Yeneneh Haileselassie, Linh P. Nguyen, Carolina Tropini, Min Wang, Laren S. Becker, Davis Sim, Karolin Jarr, Estelle T. Spear, Gulshan Singh, Hong Namkoong, Kyle Bittinger, Michael A. Fischbach, Justin L. Sonnenburg, Aida Habtezion. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host & Microbe, 2020; DOI: 10.1016/j.chom.2020.01.021

[ii] https://en.wikipedia.org/wiki/Ruminococcaceae

[iii] https://www.sciencedaily.com/releases/2020/02/200226131321.htm