A groundbreaking new study published in Nature Cell Biology has uncovered a significant molecular link between specific gut bacteria and excitatory brain signaling in the roundworm C. elegans. The study, conducted by Professor Mark Alkema and his team from the University of Massachusetts Chan Medical School, sheds light on the potential influence of diet and gut microbiota on brain health.
Scientists are increasingly recognizing the potential role of the microbiome and diet in neurological disorders such as anxiety, depression, migraines, and neurodegeneration. However, unraveling the cause and effect relationship between individual bacteria or nutrients and brain function has proven challenging.
Dr. Woo Kyu Kang, a postdoctoral fellow in the Alkema lab and the first author of the study, comments on the complexity of the gut-brain connection: “There are more bacteria in your intestine than you have cells in your body. The complexity of the brain, the hundreds of bacterial species that comprise the gut microbiome, and the diversity of metabolites make it almost impossible to discern how bacteria impact brain function.”
To overcome this complexity, Dr. Kang focused on isolating the impact of individual bacteria on specific brain functions. He fed a diet consisting of a single bacterial species to mutant C. elegans with an imbalance in excitatory/inhibitory signaling, leading to seizure-like behaviors. This genetic mutation is similar to the one found in humans that causes migraines.
The study involved testing 40 different bacterium diets, and the results revealed that 18 of them reduced the number of seizures in the worms. Further investigations revealed that the key attribute shared by several of these bacteria was their ability to produce vitamin B12.
According to Dr. Alkema and Dr. Kang, vitamin B12 reduces the levels of choline in the body. Choline is a compound found in various foods and plays a crucial role in metabolizing fat in the liver. It is also utilized in the B12-dependent methionine/S-adenosyl methionine (Met/SAM) cycle, a metabolic pathway that produces methionine, an essential amino acid for metabolism, in the intestine.
However, choline is also involved in the production of the neurotransmitter acetylcholine in the nervous system. Excessive acetylcholine can lead to an excitatory imbalance, resulting in seizure-like behaviors in mutant worms.
When higher levels of B12 are present, more choline is utilized in the Met/SAM cycle, leaving less choline available for the production of acetylcholine. This reduction in acetylcholine helps restore the excitatory/inhibitory balance in the nervous system, subsequently reducing seizure activity in C. elegans.
The researchers highlight that the impact of the interaction between the microbiome, vitamin B12, brain function, and behavior is only evident under conditions of genetic or environmental stress. In humans, B12 deficiency has been associated with neurological disorders characterized by excitatory/inhibitory imbalances, such as schizophrenia, depression, and migraine headaches.
Dr. Alkema states, “It will be interesting to determine whether the molecular mechanisms discovered in the worm can also explain the impact of B12 on excitatory signaling in several human neurological disorders.”
Moving forward, the research team plans to utilize other worm models for human diseases and explore additional metabolites and bacteria to uncover further connections between the gut microbiome and brain function. These findings may have significant implications for improving human health in the future.
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1. Source: Coherent Market Insights, Public sources, Desk research
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