Intersystems Biology

Intersystems biology builds on a decade of research in microbiome science, metagenomics, transcriptomics, metabolomics, and computational biology, and advances beyond taxonomic descriptions of microbiota to open a vast and unexplored frontier for the creation of novel medicines and drug delivery solutions.

Examples of intersystems biology are everywhere once you know where and how to look, and their impact on human health and disease is startling. When humans eat meat, the bacteria in our guts harvest the energy in their own ways, turning protein into indole metabolites like tryptophan derivatives. These molecules can act as agonists or antagonists of the aryl hydrocarbon receptor, a transcription factor for gene expression, for both good and ill. Francisco Quintana, at the Department of Neurology at Harvard Medical School, has found an axis between the gut and central nervous system in multiple sclerosis, and described how microbiota affect T cells and glial cells, controlling inflammation and neurodegeneration.

Or consider serotonin, a critical neurotransmitter. Most of it, perhaps as much as 90 percent, is found not in the central nervous system but in our guts, made by human enterochromaffin cells in response to bacterial metabolism. We depend on this gut-derived serotonin to regulate our blood glucose and appetite. If the microbiome doesn’t induce enough serotonin production, or produces too much, our health is affected in serious ways. People with low blood sugar are fatigued, weak, and sometimes confused. Hyperglycemia causes obesity and is associated with heart disease, strokes, kidney disease, glaucoma, and nerve problems.

Many people understand that plants produce anti-inflammatory and antioxidant compounds. What’s less known is that they also secrete vesicles to shepherd molecules into human cells, and that these vesicles themselves are important for human biology. For instance, essential fatty acids are part of every human cell membrane, especially in brain cells, but they can’t be made by human cells. Instead, they come from plant lipid membranes, like those that make up secreted plant vesicles. The lipids from these vesicles from fruits and vegetables are fundamental building blocks for our human cells.

Intersystems biology crosstalk can even amplify or mute the effects of nonnatural molecules like drugs. Bacteria transform drugs into more absorbable or bioactive forms, as bacterial azoreductase enzymes do to the anti-inflammatory drug sulfasalazine. Or they can break them down before they reach their intended target, as H. pylori does to levodopa, a treatment for psychosis and Parkinson’s disease. Other bacteria inactivate gemcitabine, a chemotherapeutic for pancreatic cancers. Most dangerously, bacteria can increase the toxicity of drugs, as Clostridium difficile does by producing p-cresol, which reduces the liver’s ability to metabolize acetaminophen.