High-fat diets cause gut bacteria to enter brain, Emory study finds

With more than 100 million neurons in the digestive tract, the gut is commonly known as the “second brain” in numerous cultures, including ancient Greece, Japan, China and India, linking digestion with physical and mental well-being.

Now, a new study from Emory University explains the gut-brain connection, indicating that live bacteria from the gut can directly enter the brain, with potential implications for neurological health.

Published in PLOS Biology in March, this study, performed using mouse models, establishes that live bacteria from an imbalanced gut microbiome can enter the brain via the vagus nerve. Responsible for critical functions, such as heart rate and breathing, the vagus nerve connects the brainstem to the heart, lungs, and major abdominal organs, including the stomach, intestines, liver and more.

“One of the biggest translational aspects of this study is that it suggests that the development of neurological conditions may be initiated in the gut,” says David Weiss, Ph.D., co-principal investigator of the study. 

“This may shift the focus of new interventions for brain conditions, with the gut as the new target of the therapy. That potential anatomical shift of the target could have an unbelievable impact on how people with neurological conditions benefit from therapies,” adds Weiss, a microbiologist and professor at Emory University’s School of Medicine.

During this study, a group of germ-free mice consumed a “Paigen’s Diet,” similar to a Western Diet, with a 45% carbohydrate and 35% fat content, for nine days. These diets in humans are known to contribute to intestinal permeability or a “leaky gut” where compounds can escape the intestine.

The resulting gut microbiome changes seen in the mice were associated with increased intestinal barrier permeability, or leakage, enabling live bacteria to travel from the intestine directly to the brain via the vagus nerve, without any detectable amounts of bacteria in the blood or other organs. 

Reinforcing this concept, researchers administered antibiotics, which kill many gut microbes, to these mice for three days. The mice then consumed an engineered bacterium, a barcoded Enterobacter cloacae with a DNA sequence not normally found in these bacteria in nature. When the mice were also fed the high-fat diet, this exact barcoded strain was later detected in the vagus nerve and brain of the mice. 

The study also emphasizes that stringent methods were employed to prevent cross-contamination and that the bacterial loads in the brains were low, within the hundreds, ruling out sepsis or meningitis.

Researchers also identified low-levels of bacteria in the brains of mouse models of neurological diseases, such as Parkinson’s Disease, Alzheimer’s and more, potentially explaining how these conditions may be initiated in humans.

“This research highlights the need for further study into how dietary shifts have a huge influence on human behavior and neurological health,” says Arash Grakoui, Ph.D., co-principal investigator of the study, and professor of medicine, microbiology and immunology at Emory University. 
 

Grakoui also noted that returning these mice to a normal diet restricted bacterial load in the brain by decreasing gut permeability, indicating that the impact of a high-fat diet on bacteria reaching the brain can be reversible. 

 

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