Written by | My Close Friend, Old Red Hat
The impact of gut microbiota on human functionality has been increasingly validated by numerous studies, leading to a growing acceptance of methods to improve human health through gut microbiota regulation. Probiotics, prebiotics, and dietary fibers are the most widely accepted products. Previously, it was understood that prebiotic polysaccharides and dietary fibers are indigestible by the human body; they enter the gut and can be utilized by gut bacteria, thereby regulating the gut microbiota and human functionality.[1-6]
On June 27, 2022, a research group led by Jeffrey I. Gordon from the Edison Family Center for Genomics and Systems Biology in St. Louis, USA (co-authored by Nathan D. Han and Cheng Jiyie) published an article titled Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans in Cell. Their results revealed a new function of probiotics, providing a new “definition” for prebiotics and dietary fibers.
First, the authors injected 14 different human symbiotic bacteria into germ-free mice, providing a high-fat, low-fruit-and-vegetable diet, and dividing them into an orange fiber group and a corresponding control group. After 21 days, the authors analyzed the feces of the mice using liquid chromatography-triple quadrupole mass spectrometry (LC-QqQ-MS) and found that the feces of the mice with gut bacteria receiving orange fiber contained a large amount of N-methylserotonin. However, it was undetectable in the germ-free mice. So, where did N-methylserotonin come from? Is it synthesized by gut bacteria or derived from orange fiber?
The authors found that after applying fiber-degrading enzymes to the orange fiber, N-methylserotonin was detected in large quantities, proving that N-methylserotonin was encapsulated within the orange fiber and could not escape easily. Subsequently, the authors co-cultured 50mg of orange fiber with various gut symbiotic bacteria. The highest levels of N-methylserotonin were obtained when co-cultured with Bacteroides ovatus, confirming that gut bacteria, upon encountering indigestible orange fiber in the gut, can break it down and release N-methylserotonin. What effect does the N-methylserotonin released by specific gut bacteria have on the host?
The authors administered N-methylserotonin orally to mice on a high-fat diet and found that it could reduce fat tissue, improve liver gluconeogenesis, and regulate gut rhythm to enhance gut motility. Interestingly, these effects are what we expect dietary fibers to achieve. In other words, what we thought prebiotic dietary fibers could provide—improving constipation, enhancing gut motility, and reducing fat accumulation—can also be achieved by N-methylserotonin, which is encapsulated within orange fiber and cannot be freely released! This research offers us a new perspective: the efficacy of prebiotics and dietary fibers should not only be considered from the perspective of indigestible polysaccharides but also take into account the effects of other natural compounds they contain that can be released by gut microbiota.
Finally, the authors studied the specific molecular mechanism by which Bacteroides ovatus releases N-methylserotonin from orange fiber. Through functional genomic analysis and other methods, they discovered that carbohydrate-active enzymes (CAZymes), such as PL9, are the main mechanism for releasing N-methylserotonin. In human experiments, the levels of N-methylserotonin in human feces were highly positively correlated with carbohydrate-active enzymes (CAZymes) like PL9.
In summary, the authors’ most significant finding is that the dietary fiber prebiotics we commonly encounter should not be thought of solely from the perspective of polysaccharides; they also contain a large number of natural compounds. Specific human gut bacteria can release these encapsulated natural compounds from dietary fibers in the human gut, affecting human health. This discovery provides new ideas for the future design and production of new probiotics, prebiotics, and dietary fibers.
https://doi.org/10.1016/j.cell.2022.06.004
Editor: Eleven
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