Medical researchers at Southwestern Medical Center, Utah, performed precision editing on bacterial populations in the gut. This reduced the severity of inflammation and colitis in mice.
The potential strategy was to target metabolic pathways that are active only during intestinal inflammation, preventing or reducing inflammation in mice with colitis. At the same time, no obvious effect was observed in control animals with healthy, balanced bacterial populations.
This path-breaking discovery was published in latest issue of Nature magazine.Our results present a conceptual framework for precisely altering bacterial species, which line the gut and reduce inflammation caused by colitis and other forms of inflammatory bowel disease [IBD].
In this experimental study, a form of tungsten, a heavy metal that is dangerous in high doses, was used. It was never safe to ingest heavy metals. Our primary goal was to identify a safe therapy that exerts a similar effect.
There is a diverse population of microbes, which form a thin line on the intestinal tract. These microbes are essential for the maintenance of good health. They help in digestion, improve the immune system, and fend off infections.
When there is an imbalance in microbial populations, these beneficial bacteria become a liability as they become invasive and push out competing species. It is difficult to understand the biology of gut microbiota thanks to its vast diversity.
In humans, several different species of bacteria were found in the intestinal tract. The composition of species differs extensively for individuals.The composition of gut microbiota changes considerably, causing many chronically progressive diseases, such IBD, Crohn’s disease, and ulcerative colitis.
According to Centers for Disease Control and Prevention, at least 1 million adults in the United States of America are affected by IBD. Currently, there is no cure for such diseases. Changes in gut microbiota also occur in patients with Type 2 diabetes, colon cancer, HIV-related intestinal disease, and necrotizing enterocolitis. These diseases are also observed in certain premature infants.
Bacteria found in the gut microbiota belonged to enterobacteriaceae family, causing many inflammatory diseases. In healthy gut, a small number of healthy bacteria are present. They belong to E.coli (Escherichia coli). These bacteria also protect pathogenic bacteria, such as Salmonella, which is the cause of food poisoning. In mouse models of colitis, there is uncontrolled growth of enterobacteriaceae species.
In a paper published by Cell Host & Microbe, it was reported that cellular energy was produced by Enterobacteriaceae family. Gut bacteria uses this energy for improving growth and obtaining nutrients. Unique metabolic pathways were used to improve the growth and drive out beneficial bacteria at the time of illness.
These unique pathways are used to improve inflammation in gut. In current study, heavy metal tungsten was used to inhibit pathways obstructing metabolism. An inflammation develops due to incessant growth of pathogenic bacteria.
These researchers have reported that tungsten was absorbed by bacteria, and an important bacterial cofactor was incorporated. Under such circumstances, enterobacteriaceae loses its ability to generate energy due to inflammation.
Tungstate was orally administered in the form of a soluble tungsten salt. Beneficial bacteria were not affected in this innovative experiment. This is because a particular cofactor cannot govern the metabolism of beneficial bacteria.
The proliferation of enterobacteriaceae was stopped in our current experiment. When enterobacteriaceae species were present in correct ratios, colonization would be resisted by bacterial pathogens.
By controlling the proliferation of bacteria, inflammatory episodes were prevented completely. With miniscule experimental evidence, it can be postulated that diseases of the gut worsen due to changes in the composition of microbiota.
In this study, it was found that inflammation of the gut was reduced and a normal state was achieved using tungstate treatment. In most experiments, tungsten was used to rectify a molecular target. This treatment was therapeutic for patients. At the same time, tungsten is the heavy metal that provokes neurological and reproductive diseases.
Conventional approaches are focused on treating pathogenic bacteria. However, this path-breaking research is quite useful to harness bacteria in the normal gut. The composition and function of gut microbiota was controlled.
Most doctors prescribe broad spectrum antibiotics. The final objective is to tarnish numerous bacteria in the gut. Whenever a patient visits the clinic in a critical state, most doctors prescribe antibiotics as there is no time for identifying specific pathogen. In such a scenario, broad-spectrum antibiotics kill most pathogens along with beneficial bacteria.
Only one family of bacteria, enterobacteriaceae, was targeted in our study. Although results are promising, more studies must be conducted to identify potential therapies that cause human diseases.