Recent research has indicated that antibiotic-resistant forms of a bacteria known as Klebsiella may be playing a role in causing the chronic inflammation of the intestinal tract. This information comes from a recent study entitled “Ectopic colonization’s of oral bacteria in the intestine drives Th1 cell induction and inflammation.”
The study was recently published in the Science journal and was led by Koji Atarashi of Keio University School of Medicine in Tokyo, Japan. The research team included Ramnik J. Xavier, and Heba S. Said et al.
To help lay some groundwork for the study results, we need to understand that the bacteria highlighted in this study is Klebsiella. From Microbe Wiki, we learn that various forms of Klebsiella are “naturally found in many parts of the human body, to include the mouth and intestines.” We also learn there are different strains of Klebsiella in the body.
Why these particular bacteria are emphasized in the study’s scientific report will become clear as we review the actual report.
The study's bottom line
The bottom line of this article is that an international research team gathered together to study why people and lab mice with chronic gut troubles tended to have larger than normal amounts of oral-type bacteria in their feces. The scientists were able to isolate and identify the bacterial culprit and also to demonstrate its connection with intestinal disorders such as Crohn’s.
The research team taking on this study were exceptionally suited for the task.
Introduction to the research team
First, via the Harvard Magazine, we are introduced to the study’s coauthor: Ramnik Xavier, M.D., an accomplished U.S. member of the team. As chief of gastroenterology at Massachusetts’s General Hospital (MGH), he is co-author of this international research project. Dr. Xavier is also a member of the Broad Institute at Harvard and Massachusetts’s Institute of Technology (MIT). (According to Wikipedia, The Broad Institute is “a biomedical and genomic research center located in Cambridge, Massachusetts.”)
Dr. Xavier is also co-director of MIT’s Center for Microbiome Informatics and Therapeutics. Work there centers on “the full collection of microbes (Bacteria, Fungi, Virus, etc.) that naturally exist within an organism.”
Joining the team with Dr. Xavier were researchers from the Middle East who had noticed a recent sharp rise in IBD and Crohn’s in their Middle Eastern region. These scientists included Doctors Koti Atarash, and Heba S. Said.
When researchers isolated the proliferation of Klebsiella bacteria in the feces excreted by the humans and mice in the research study, they found a large number of mouth-derived Klebsiella bacteria in the colonies. The team was able to differentiate the strain and identified it as the antibiotic-resistant Klebsiella Pneumoniae strain- 2H7(Kp-2H7).
According to Ars Technica, the team suspected that the transfer of this oral bacteria to the intestinal tract occurred with the normal process of swallowing. Once in the intestinal tract, it was surmised, certain conditions created a breeding ground for this bacterial strain and triggered inflammatory bowel conditions such as Crohn’s.
We are also informed by the study overview that the scientists then set out to test this theory.
Dr. Xavier said while researchers have tested for this or that bacteria as a possible contributor to Crohn’s, for many years, “There’s always been this other search, asking ‘Are there pathobionts?’- in other words, microbes that live innocuously in one part of the body but can turn pathogenic when moved to another?” (Harvard magazine)
The researchers used “germ free’ mice for the experiment. (According to Wikipedia, Germ-free animals are animals that have no microorganisms living in or on them. Such animals are raised within germ-free isolators in order to control their exposure to viral, bacterial or parasitic agents.)
Research method and findings
The team tested their theory by having germ-free mice ‘take in’ a mucus sample from two people with Crohn’s. One sample had no effect o he mice, but the other caused “a raging immune response in the rodents’ intestines.” Through microbiology testing, the team identified the antibiotic-resistant 2H7 (kp-287 strain).
“Drug resistance occurs when bacteria, like Klebsiella, change so that certain antibiotics don’t kill them anymore,” per the PA Department of Health.
Increasingly, Klebsiella has been found to be resistant to the class of antibiotics known as carbapenems”. Examples of this class of antibiotics include imipenem, panipenem, and doripenem. Klebsiella’s non-response to many antibiotics, now to include carbapenems, is disconcerting. Carbapenems is reserved for the treatment of “super drugs” that are resistant to multiple bacteria (such as the Klebsiella family). (Wikipedia) Antibiotic resistance brings challenges to the treatment of Klebsiella.
To further test the research team’s theory that Klebsiella is somehow involved with intestinal inflammation, and to get all the information they could gather in the experiment, they found that Kp-2H7 wouldn’t grow in the intestines of healthy wild mice. However, by giving the mice antibiotics that the 2H7 (Kp-2H7) bacteria was resistant to, the growth of Klebsiella took off, and led to persistent episodes of inflammation, as well.
On a roll, the team repeated their testing again. This time, they collected saliva samples from people with ulcerative colitis. The results showed increased inflammation in some of the ‘healthy’ mice. This time, however, the causative bacteria was found to be also be Klebsiella, but of a different strain: Klebsiella aeromobilis, 11E12 (Ka-11E12).
Research perspective and conclusions
As noted in the Science abstract, genetics supposedly play a part in the process: the tendency toward initiation of the inflammatory process requires the presence of a "genetically susceptible host."
Therefore, the researchers concluded that genetics and microbiome-disturbing factors such as antibiotics play a role in the development of inflammatory conditions. And, that intestinal pathogens trigger recurring bouts of inflammation with IBD conditions such as Crohn’s and ulcerative colitis.
From the article just referenced, researchers have identified drug-resistant Klebsiella pneumonia strain (Kp-2H7) and Klebsiella aeromobilis (Ka-11E12) as agents that “provoke abnormal immune responses and inflammation.”
Per Medscape, Klebsiella cells are pesky and obnoxious. Their cell body is encased in a capsule, highly resistant to antibiotics and to natural body mechanisms such as the immune system.
What is now known is that individuals with inflammatory bowel diseases have significantly higher amounts of Klebsiella strains in their feces vs. people without IBD conditions.
In relation to this finding, team member Xuetao Cao, an immunologist of the Chinese Academy of Medical Sciences concludes: “The data strongly indicates the pathogenic role of oral cavity-derived Klebsiella strains” present in the bacterial colonies of the mouth, “may have a future in helping to treat such conditions.”
It is also noteworthy that the research showed a high level of T-cells in the blood of some of the tested cohorts. T-cells play a major role in the response to invader cells and are thought to be yet another indicator of the presence of over-abundant Klebsiella in the intestinal tract.
In closing, we are informed that the complex community of microorganisms in one’s gut, known as the gut microbiome, consists of more than tens of trillions of microorganisms that are important for physiological functions like digestion.
“Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.”