By: Pooja Sharma
A new startling discovery from a California-based team of researchers has pointed out that small bacterial infections, such as those that occur during mild food poisoning and are treated without any antibiotics, can start a chain of events inside your body and lead to chronic inflammation in gut and can also cause life threatening colitis. These mild infections, such as E. coliand Salmonella, sometimes go unnoticed, but a breakthrough research has now proven the consequences it might have on us in the long term. The discovery was published in Scienceand revealed how the past history of minor bacterial infections can ultimately lead to cause a severe inflammatory disease. These new findings might be able to decipher the origins of Irritable Bowel Syndrome whose origins have been quite mysterious.
Researchers worked for a total of 8 years until they found out that Recurrent Food Poisoning can trigger a pro-inflammatory enzyme that can, in turn, hamper the body’s ability to be able to detoxify resident normal gut bacteria. The California team of researchers that were led by Jamey Marth of UC Santa Barbara’s Centre of Nanomedicine and Sanford Burnham Prebys Medical Discovery Institute hypothesized that continuous low level bacterial infections can in long term lead to some chronic disease. Other lead authors included were Michael Mahan, Douglas Heithoff, Peter Aziz, Won Ho Yang. The research was done in collaboration with Victor Nizet of UC San Diego and Markus Spendario of Ludwig-Maximilian University of Munich. Trying to determine the underlying cause of a disease is crucial as it can lead to more effective and rational preventions, research, and treatment in the field.
The Research Work:
Hypothesis: The hypothesis for the experiment was based on multiple clues. First was the genetic makeup of an individual playing a limited role in the onset of Inflammatory Bowel disease and also, twins showing low concordance of developing IBD’s individually. Such findings made it increasingly evident for some other factors influencing the onset of inflammatory diseases in humans.
Second, there were several studies that pointed out that repeated seasonal infections in some individuals were correlated with increased diagnosis of IBD.
Experiment: The researchers started off by developing a model using healthy mice of mild food poisoning. They were administered a very low dose of a common bacterial pathogen called Salmonella Typhimurium. This organism is quite widespread throughout the environment and remains the leading cause of foodborne illnesses in the US. Salmonella is responsible for around 1 million foodborne illnesses that occur in the US each year. The most common symptoms of Salmonella include some temporary intestinal discomfort and dysfunction which generally do not require any treatment. Majority of Salmonella infections are not reported which means that the number of times an individual contracts an infection is a lot underestimated.
The bacteria was fed to the mice from every four weeks to 6 months. The dose of Salmonella that was given was so low that there were no significant symptoms or deaths in the mice and the Salmonella was successfully eliminated by the host. So, the reaction was initially asymptomatic but as the feedings were increased, the mice became increasingly symptomatic.
This type of study was one of its kind and has never been done before. The results were quite surprising as well. There was an onset of progressive and irreversible inflammatory disease due to previous infection which had been already completely eliminated by the host.
By the time of the fourth infection (they were separated by months apart from the previous ones) – inflammation has slowly and steadily increased throughout the infections and all the subjects were suffering from colitis. And to the surprise of the scientists, the disease did not show any improvements despite the cessation of repeated infections. This meant that the damage was already done.
Why this happens?
Salmonella has figured out a way to disrupt one of the unknown protective mechanisms of the gut that helps in preventing intestinal inflammation. The underlying cause of the disease is as follows: Cells in the duodenum (the first part of the small intestine) was no longer producing IAP or intestinal alkaline phosphatase. IAP is responsible for detoxifying the harmful lipopolysaccharide (LPS) toxin that is produced by Salmonella or any other gram-negative bacteria. It transforms LPS from toxic to non-toxic state. This happens because Salmonella induces another enzyme called Neuraminidase (Neu), resulting in IAP deficiency. Neu activity accelerates the molecular aging and turnover of IAP, which leads to IAP deficiency in colon.
However, the good news is that there are ways that can easily boost up the IAP levels and inhibit neuraminidase activity in the colon. A potential treatment that was done during the experiment was feeding the mice with calf intestinal alkaline phosphatase (cIAP) showed positive effects both for normalization of levels and preventing the animals from developing symptoms. So, basically there are existing methods to cure the root of this problem. IAP augmentation is a fairly simple process too. The inhibition of Neuraminidase (Neu) can easily be achieved by using currently marketed anti-viral neuraminidase inhibitor. It is a drug that is currently used to prevent influenza viral infections.
This is a striking discovery in the field of food science. IBD and colitis that is induced by recurrent infections can be easily prevented by giving alkaline phosphatase or antiviral. Even though it still remains unclear on whether or not the treatment would be effective after the chronic inflammation has developed.
In a recent article in Forbes magazine concerning the study, Dr. Marth explained, “Remarkably, Salmonellae have figured out a way to disrupt a previously unknown protective mechanism in the gut that normally prevents intestinal inflammation.” In the same interview, Dr. Yang added, “We observed the onset of a progressive and irreversible inflammatory disease caused by previous infections. That was quite surprising because the pathogen had been easily cleared by the host.” The article went on to quote Dr. Mahan that “others have recently reported IAP deficiencies and high neuraminidase levels in IBD patients.” As more studies unfold, science is starting to see more and more patterns related to food borne illnesses and long-term complications stemming from them.