A team of researchers from The Rockefeller University and the Icahn School of Medicine at Mt. Sinai have described a method for engineering gut bacteria with therapeutically beneficial effects on disease. The research was published this week in the journal Nature.
The paper introduced two innovative concepts in the study and use of gut bacteria. The first was that gut bacteria and human cells use the same ligands to send chemical messages, allowing them to speak what is essentially the same chemical language. The second was that this shared language would allow them to genetically engineer bacteria that produce molecules to treat certain disorders by altering human metabolism.
As proof-of-concept, the scientists introduced modified gut bacteria to mice that caused a reduction in blood glucose levels and other metabolic changes.
In the paper, the scientists described their method as ‘mimicry’. The molecules they chose to mimic with the engineered bacteria were human ligands that bind to G-protein-coupled receptors (GPCRs). GPCRs are implicated in metabolic diseases and are common targets of drug therapy. Significantly, they can also be found in the intestinal tract where gut bacteria are also found.
The gut bacteria in this study were engineered to produce N-acyl amide ligands that bind to the human receptor, GPR 119, which is involved in regulating glucose and appetite, and is a known target for treating diabetes and obesity. The engineered ligands were almost identical to the human ligands in structure.
To isolate the human gut bacteria, the researchers used human stool samples. Once the bacteria were isolated, they were cloned and packaged inside E. coli bacteria. The researchers noted that bacteria are convenient to work with as their genes are easier to manipulate than human genes and much is already known about them. In the case of gut bacteria, they already exist in symbiosis with humans and thus can be more easily incorporated into human systems.
The researchers believe this concept holds great promise for future therapies using engineered bacteria.
Image courtesy of the Rockefeller University