The bacteria living in the human gut function almost like a second liver, changing how we metabolize glucose and amino acids, according to a new study.
Thousands of Bacterial Species
The microbiome is a buzzword these days, but it has been around for as long as humans have. This microbial community is made up of a combination of bacteria, viruses, fungi, and other microscopic organisms living in the mouth, intestines, skin, and beyond. Most microbes in the gut microbiome live inside the cecum, a “pocket” of the large intestine. There are up to 1,000 species of bacteria in the gut microbiome, each with a different role.‘A Second Liver’
In the study, the Weill Cornell Medicine research team examined how gut microbiota extract nutrients and vitamins from food.“They ‘eat’ before us, taking first dibs on the nutrients from the food we consume, and leaving us with what remains after they satisfy their own nutritional needs,” Guo Chun-Jun, senior author of the study and assistant professor of microbiology and immunology in medicine, said in a statement.
Mr. Guo and his team looked at how efficiently different bacteria living in the intestines use up amino acids. Amino acids are building blocks the body uses to make proteins, break down food, grow and repair body tissue, make hormones and brain chemicals, support the immune system, and more.
After screening more than 100 different human gut microbes, researchers found several that excelled at metabolizing multiple amino acids. Then, they identified specific bacterial metabolic genes that drain amino acids.
They realized quickly that the list of genes affecting amino acid depletion was long.
“We found that in one single bacterium, there are over 20 different genes encoding a similar enzymatic function,” Mr. Guo said in the statement.
Using what’s known as CRISPR technology, the team was able to perform a large gene deletion screen and identify the genes responsible for exhausting amino acid stores. By manipulating those individual genes, the researchers could determine how the genes’ function affected amino acid regulation. They then injected modified strains of bacteria into germ-free mice and were surprised by the results.
The mice’s gut microbiomes began to consume a specific class of amino acids and altered glucose levels in the process. Further analysis showed that changing how many amino acids were available produced a chain reaction: Serotonin production was altered, resulting in a change in how glucose was regulated.
Manipulating the Microbiome to Regulate Metabolism
The research team is looking to form new, more precise ways to modify these bacterial enzymes and examine how different bacteria combinations will affect amino acid metabolism in the host.Some of the genes that Mr. Guo’s team studied are the same genes that are dysregulated in the gut microbiomes of people with metabolic and gastrointestinal diseases. Engineered types of bacteria or drugs that target certain microbial genes may provide new options for treating these conditions, Mr. Guo said.
“These metabolic genes might be potential biomarkers for diseases like type 2 diabetes or inflammatory bowel disease, and they are also potential treatment targets,” he said. “Our research demonstrates the possibility of precisely manipulating gut microbiota to regulate host metabolism and improve host metabolic functions.”
