Perianal fistulizing Crohn’s disease (PCD) is a complication of Crohn’s that affects up to 40% of Crohn’s patients. Fistulas form when abnormal connections form between the intestine and surrounding tissue.  Specifically, in the presence of inflammation, ulcers extend through the entire intestinal wall, creating a tunnel that drains pus away from the inflamed area. Fistulas may occur anywhere along the GI tract and are very painful and difficult to treat.

In good news for patients, a 2025 study published in The Journal of Clinical Investigation identifies new factors that contribute to fistulas. Examining samples of patients with PCD, researchers found that a specific immune signal--interferon gamma (IFN-γ)—was highly active in patients with PCD. This over-activation was linked to inflammation and changes in tissue that allow fistulas to form and persist.

The study also identified high numbers of a type of white blood cell, Th17 immune cells, which help protect the body from infections. In PCD, however, these cells produced large amounts of IFN-γ, fueling inflammation and tissue damage. Together with other immune cells, they created a cycle that drives fistula formation.  Combined, these new findings may pave the way for more effective treatments of fistulas and much needed relief for patients.

References

​Crohn’s & Colitis Foundation

Revealing hyperactivated IFN-γ pathways in perianal fistulizing Crohn’s disease using single-cell and spatial multi-omics, J Clin Invest. 2025; 135(17):e193413.

​A study published in the Gastroenterology journal by a Canadian research team documents that population and ratios of specific gut bacteria are uniquely different in those patients who develop Crohn’s disease as opposed to those who do not, and this gut bacteria differentiation can be identified years before Crohn’s Disease symptoms develop.
 
Dysbiosis involving five key bacteria contributed to subsequent Crohn’s Disease.  The five bacteria are:  “Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia.”  (https://pubmed.ncbi.nlm.nih.gov/37263307/)
 
The discovery constitutes two important advances.  First, it provides clinicians with the ability to identify the bacteria populations that make one prone to development of Crohn’s Disease based upon identification of bacteria in one’s microbiome.  Second, with the specific bacteria now identified, clinicians can intervene in advance of symptoms to increase the population of good gut bacteria and decrease the population of the bacteria that instigate Crohn’s Disease.
 
One of the study’s authors, Dr. Kenneth Croitoru, told Crohn’s and Colitis Canada that “These years of effort led us to recently discover that a specific combination of gut bacteria is connected to the future development of Crohn’s disease. We’re starting to see the pattern of bacteria that may be triggering Crohn’s disease, moving us closer to better treatments for those with the disease or even preventing it for those at risk. I’m hopeful that within five years, patients will benefit through evidence-based treatments focused on the gut bacteria or diet modification.”   (https://crohnsandcolitis.ca/News-Events/News-Releases/Canadian-medical-research-breakthrough-Gut-bacteri).

​Traditionally it has been difficult for researches to study bacterial population changes in the small bowel, as they are only reachable during surgery or endoscopy.  Now, researchers led by Andrew Macpherson and Bahtiyar Yilmaz from the Department for Biomedical Research at the University of Bern and the University Clinic for Visceral Surgery and Medicine at the Inselspital have used patients with ileal ostomies as a means to survey the small bowel microbiome in real-time, leading to some interesting discoveries. 
 
Among the findings, ileal bacteria populations are highly variable, largely disappearing when individuals fast while sleeping overnight, only to bloom again when food is consumed at breakfast.  Interestingly, while the number of bacteria fluctuates significantly, the types of bacteria that comprise the microbiome do not.  The changes that occur in the bacterial populations also happen quickly, within hours of consuming a meal.  This differs from the bacteria in the large bowel, whose numbers and proportions remain stable.
 
The head of the study and its senior author, Andrew Macpherson, stated that "Because the system is so flexible, each bacterial species can adapt to a changing environment in the small intestine by changing the proportions of subspecies and thus prevent the species as a whole from dying out." As a result the ileal bacteria normally avoid species extinctions, unless there is an illness, malnutrition, or other environmental factor. 
 
These findings, and the use of small bowel ostomies as a research tool, will enable further research into the interaction of the small intestine microbiome and diseases like Crohn’s, Colitis, and celiac.  
 
(Plasticity of the Adult Human Small Intestinal Stoma Microbiota. Cell Host & Microbe, 2022; DOI: 10.1016/j.chom.2022.10.002).

​University of Gothenburg researchers have found a statistically significant risk of pre-term births to mothers who are Inflammatory Bowel Disease (IBD) patients.  IBD, including Crohn’s Disease and Colitis, causes visible inflammation and damage to the intestinal lining.  The new research indicates that even microscopic inflammation in a patient who might otherwise be considered to be in remission, has adverse implications for pre-term pregnancies.
 
Karl Mårild, the study's first author and corresponding author and an associate Professor of Pediatrics at Sahlgrenska Academy, University of Gothenburg, and senior consultant pediatrician at the Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, stated:  "Our results suggest that IBD treatment aimed at not merely alleviate symptoms of IBD, but also microscopically heal the intestine, can reduce the risk of giving birth preterm. If our results hold up in future studies, they may therefore be the basis for recommendations to confirm microscopic healing before pregnancy, to reduce such risks."

The Summer 2019 issue of MIT Spectrum reports on the travels of several MIT post-doctoral students who traveled to Malaysia in search of microbiome samples from indigenous villagers of the Batek tribe.  Collecting the samples proved to be challenging, as skeptical villages unaccustomed to toilets, not to mention observers, were unwilling to  put their personal habits on display.  Fortunately an accommodation preserved the villagers' privacy while allowing the researchers to locate stool samples.

Although it sounds at first like an odd undertaking, the fact is that the Batek tribe living in the forest more than 250 miles from the capital in Kuala Lumpur offered a unique microbiome.  As nomadic hunter-gatherers, the Batek tribe's microbiomes are the result of a diet free from processed food, and untouched by the vaccines, antibiotics, and chemicals that affect the microbiomes of those living in the industrialized areas of the globe.  

The successfully harvested samples were taken to MIT's Center for Microbiome Informatics and Therapeutics (CMIT) for further study.  Launched in 2014, CMIT seeks to research the human microbiome to understand better its role in the diagnosis, treatment, and prevention of diseases like Crohn's Disease and Ulcerative Colitis.  


Source:  Halber, Deborah, "Going for the Gut," MIT Spectrum, Summer 2019 Issue, available at:  https://spectrum.mit.edu/summer-2019/going-for-the-gut/

Most everyone knows, or should know, that orally administered antibiotics destroy vast numbers of both the good and harmful bacteria that comprise the microbiome.  Recent research has shown that the microbiome is also vulnerable to more than two hundred other medications that are not specifically antibiotics, like blood pressure medication, antihistimines, and painkillers.

The research, undertaken by the European Melocular Biology Laboratory in Heidelberg, Germany, was made possible by new techniques that permit the culture of anaerobic bacteria that live only in the absence of oxygen -- like those in the microbiome.  

The research also found that the same bacteria that were resistant to antibiotics were also resistant to adverse effects from other medications.  An important revelation of this research is that antibiotic resistance can occur even when antibiotics are not used.  

For Crohn's Disease patients, this is important news.  Ensuring a healthy microbiome is an essential approach to ensuring that a dysbiosis in the microbiome -- a hallmark of a Crohn's Disease inflammation flare -- does not occur.  Knowing that many other medications, in addition to antibiotics, can adversely affect the microbiome is critically important. 

Source:  Maier, Lisa, et al., "Extensive Impact of Non-Antibiotic Drugs on Human Gut Bacteria," Nature 555, 623-628 (19 March 2018).

No one factor causes IBD. Instead, interactions between a multitude of factors appear to lead to IBD.  Genetic predisposition, certain environmentla factors, and imbalances of the gut's microbiome may combine to cause IBD.

IBD is more common in North America and Europe than it is in places like Asia and Africa.  However, since 1950s, IBD has been increasing all over the globe, suggesting that the adoption of more Western lifestyles may be contributing to the rise in IBD cases. 

So far researchers have found over 200 genes associated with a risk for IBD. 

TOO MUCH exposure to these environmental factors may trigger or worsen IBD:

• Pollutants
• Viruses
• Medications & Antibiotics
• Cigarette Smoking
• Higher Levels of Hygene
• Increased Stress

​

TOO LITTLE of these environmental factors may trigger or worsen IBD:

• Sleep
• Exercise
• Vitamin D/Sun Exposure

The microbiome includes the millions of bacteria, viruses, and fungi that live in our gut.  Everyone's microbiome is different, depending on what microbes a person was born with, what they ate, medications taken, and the environment.  Ongoing research is helping to show that the microbiome is a key factor in whether or not a person with genetic susceptibility will develop IBD.

Crohn's & Colitis Foundation, "Beyond Genetics: How we're unlocking the role of environmental impact on IBD," Under the Microscope, Fall 2017.