The surprisingly ingenious ways bacteria grow in the human gut

The gut microbiome is so helpful to digestion and human health that it is often referred to as an extra-digestive organ. This vast collection of bacteria and other microorganisms found in the gut helps us break down food and produce nutrients or other metabolites that impact human health in multiple ways.

New research from the University of Chicago shows that some groups of these microbial helpers are also incredibly resourceful, with a vast repertoire of genes that help them generate energy for themselves and potentially also influence human health.

The article, published on January 4, 2024 in Natural microbiologyidentified 22 metabolites that three distantly related families of gut bacteria use as alternatives to oxygen for respiration in the anaerobic environment of the gut.

These bacteria also have up to hundreds of copies of genes to produce the enzymes that process these alternative metabolites, far more than has been measured in bacteria living outside the gut. These results suggest that anaerobic gut bacteria may also have the ability to produce energy from hundreds of other compounds.

“These are examples of some particular metabolisms that act on all of these different metabolites produced by the gut microbiome,” said Sam Light, Ph.D., Neubauer Family Assistant Professor of Microbiology at UChicago and senior author of the study. .

“This is interesting because one of the main impacts of the microbiome on our health is to make or modify these small molecules that can then enter our bloodstream and act like drugs.”

At the body level, we generally think of respiration as the process of inhaling oxygen. At the cellular level, respiration describes an energy-generating biochemical process. Most cells use oxygen to breathe, but in anaerobic environments like the inside of the intestine, cells have evolved to use other molecules.

Cells have two main types of metabolism to produce energy: fermentation and respiration. During fermentation, the cell breaks down molecules to directly generate energy.

Respiration involves two molecules: an electron donor and an electron acceptor. A classic example of this process uses glucose as the donor and oxygen as the acceptor. Cells break down glucose by passing the extracted electrons through a series of steps before their final transfer to an oxygen molecule. This prompts the cell to generate ATP, or adenosine triphosphate: the basic energy source to be used and stored at the cellular level.

Most microbes living in the gut use fermentation, but there are also several known types of bacteria with respiratory metabolism, including those that use carbon dioxide and sulfate electron acceptors.

For the new study, Light and colleagues analyzed a database of more than 1,500 genomes from a database of human gut bacteria. They observed a surprising distribution of genes producing reductases, enzymes that use different respiratory electron acceptors. While most genomes encode only a few reductases, a small subset encodes more than 30 different ones.

These bacteria were not closely related; they came from three distinct and distantly related families (Burkholderiaceae, Eggerthellaceae, and Erysipelotrichaceae) separated by hundreds of millions of years of evolutionary history.

These bacteria appear to be more resourceful than bacteria whose respiratory metabolism lives outside of a host organism, which primarily use inorganic compounds. The gut respiratory bacteria identified by Light and his team specialize in various organic metabolites, which makes sense given the constant supply of food.

“There’s so much organic matter in the gut that comes from the food we eat. It’s chemically complex and it takes more enzymes to adapt it to that environment,” Light said. “We think this variety of genes allows gut bacteria to use many different things that come their way.”

Some of the metabolites they use also have interesting implications for human health in the gut. People with type 2 diabetes, for example, have higher levels of an amino acid byproduct called imidazole propionate in their blood. Another metabolite, resveratrol, impacts several metabolic and immune processes, and itaconate is produced by macrophages in response to infections.

Light hopes that more research like this will help us understand the function of different microbes in the gut, which can in turn be harnessed to improve health.

“I hope that our understanding of these different metabolisms and their functioning will allow us to propose intervention strategies, either through diet or through pharmacology, to modulate the flow of metabolites through these different pathways,” he said. he declared. “So, regardless of the context, such as type 2 diabetes or following infection, we could control which metabolites are produced to have therapeutic benefit.”