The human gut, a bustling hub of microbial activity, has long fascinated scientists for its profound impact on our health. A recent study led by the University of Chicago has unraveled another layer of this mystery, revealing the surprisingly resourceful ways bacteria thrive in the low-oxygen environment of our gut.
The research provides insights into the gut microbiome’s complexity and its significant influence on human health.
Often referred to as an “extra digestive organ,” the gut microbiome is made up of a vast collection of bacteria and other microorganisms essential for digesting foods and producing vital nutrients.
These microorganisms not only aid in breaking down food but also generate metabolites that significantly impact human health.
The study highlights how certain gut bacteria, through a vast arsenal of genes, efficiently produce energy in the oxygen-poor gut environment. This capability extends far beyond what is observed in their counterparts living outside the human body.
The study identified 22 metabolites utilized by three distantly related families of gut bacteria (Burkholderiaceae, Eggerthellaceae, and Erysipelotrichaceae) for respiration in the gut’s anaerobic environment.
Remarkably, these bacteria possess hundreds of genes for enzymes processing these alternate metabolites, a significant contrast to their extra-gut counterparts.
The results suggest that anaerobic gut bacteria may have the ability to produce energy from hundreds of other compounds as well.
“These are examples of some of the peculiar metabolisms that act on all these different metabolites produced by the gut microbiome,” said study senior author Dr. Sam Light. “This is interesting because one of the main ways the microbiome impacts our health is by making or modifying these small molecules that can then enter our bloodstream and act like drugs.”
In most environments, cells use oxygen for respiration. However, the gut’s anaerobic nature has led to the evolution of cells that utilize different molecules.
Cells can produce energy via two main metabolic processes: fermentation and respiration. While fermentation involves direct energy generation from molecule breakdown, respiration requires an electron donor and acceptor. In the gut, several known types of bacteria use carbon dioxide and sulfate as electron acceptors in their respiratory metabolisms.
The study’s in-depth analysis of over 1,500 human gut bacteria genomes revealed a surprising distribution of genes producing reductases, enzymes critical for different respiratory electron acceptors.
A noteworthy observation was that while most genomes encode only a few reductases, a subset encodes more than 30 different types.
These bacteria, belonging to diverse and distantly related families, demonstrate a resourcefulness in utilizing various organic metabolites, likely due to the gut’s constant and complex food supply.
“There is so much organic matter in the gut that comes from the food we eat. It’s chemically complex, and you need more enzymes to accommodate it in that environment,” said Dr. Light. “We think this variety of genes enables gut bacteria to use a lot of different things that come their way.”
Some of the metabolites have intriguing implications for human health. For instance, higher levels of the amino acid byproduct imidazole propionate are found in people with type 2 diabetes. Other metabolites like resveratrol and itaconate play roles in metabolic and immune system processes.
Dr. Light hopes that more research like this will help us understand the function of different microbes in the gut, which can be used to improve health.
“I’m hoping our understanding of these different metabolisms and how they work will enable us to come up with strategies to intervene – either through the diet or pharmacologically – to modulate the flow of metabolites through these various pathways,” said Dr. Light.
“So, in whatever context, like type 2 diabetes or following an infection, we could control which metabolites are being produced to have a therapeutic benefit.”
The study is published in the journal Nature Microbiology.
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