Tag: gut-brain axis

Categories : Neurodegenerative DiseasesTags :

Researchers Uncover Major Contributor to Alzheimer’s Disease

On By ModernMedia
Gut microbiome. Credit: Darryl Leja, NIH

Research reports for the first time a pathway that begins in the gut and ends with a potent pro-inflammatory toxin in brain cells contributing to the development of Alzheimer’s disease (AD). Results are published in Frontiers in Neurology, where the researchers also report a simple way to counter the process.

The researchers, led by Drs Yuhai Zhao and Walter J Lukiw, found evidence that a molecule containing a very potent microbial-generated neurotoxin (lipopolysaccharide or LPS) derived from the Gram-negative bacteria Bacteroides fragilis in the human gastrointestinal (GI) tract generates a neurotoxin known as BF-LPS.

“LPSs in general are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known,” explained Dr Lukiw. “Many laboratories, including our own, have detected different forms of LPS within neurons of the Alzheimer’s disease-affected human brain.”

The researchers detailed the pathway of BF-LPS from the gut to the brain and its mechanisms of action once there. BF-LPS leaks out of the GI tract, crosses the blood brain barrier via the circulatory system, and accesses brain compartments. Then it increases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L,) a protein that supports cell integrity. A deficit of this protein leads to progressive neuronal cell atrophy, and ultimately cell death, as is observed in AD-affected neurons. They also report that adequate intake of dietary fibber can head off the process.

The novel features of this newly described pathological pathway are threefold. The AD-stimulating pathway begins in the gut microbiome and therefore is very “locally sourced” and active throughout our lives. The highly potent neurotoxin BF-LPS is a natural by-product of gut-based microbial metabolism. Bacteroides fragilis abundance in the microbiome, which is the source of the neurotoxin BF-LPS, can be regulated by dietary fiber intake.

“Put another way, dietary-based approaches to balance the microorganisms in the microbiome may be an attractive means to modify the abundance, speciation, and complexity of enterotoxigenic forms of AD-relevant microbes and their potential for the pathological discharge of highly neurotoxic microbial-derived secretions that include BF-LPS and other forms of LPS,” Dr Lukiw explained.

The researchers conclude that an improved understanding of the interaction between the Gut–Brain axis and the gut microbiome and Alzheimer’s disease has considerable potential to lead to new diagnostic and therapeutic strategies in the clinical management of Alzheimer’s disease and other lethal, progressive, and age-related neurodegenerative disorders.

Source: Louisiana State University Health Sciences Center

Categories : Gastrointestinal Mental HealthTags :

IBD and Depression is a Two-way Street

On By ModernMedia
Photo by Andrea Piacquadio on Pexels

While irritable bowel disease (IBD) and depression are known to occur together, scientists report a clinical overlap of these conditions in the Journal of Gastroenterology and Hepatology, implying the existence of a two-way relationship. Patients diagnosed with IBD were nine times as likely to develop depression than the general population. Their siblings who did not suffer from IBD were almost two times as likely to develop depression.

Conversely, patients with depression were two times as likely to develop IBD, and their siblings without depression were more than one and a half times as likely to develop IBD.

“This research reveals a clinical overlap between both conditions, and is the first study to investigate the two-way association between IBD and depression in siblings,” said Bing Zhang, MD, a gastroenterologist with Keck Medicine and co-lead author of the study.

The researchers drew on the data of more than 20 million people from Taiwan’s National Health Insurance Research Database. For 11 years, they tracked patients with either IBD or depression and their siblings without either condition, comparing onset of depression or IBD with a control group of people without either condition, but with similar age, sex and socioeconomic status.

Zhang hypothesises that many factors may contribute to the bidirectional nature of the disorders, including environmental stressors, the gut microbiome and genetics.

“The finding that people with IBD are more prone to depression makes sense because IBD causes constant gastrointestinal symptoms that can be very disruptive to a patient’s life,” he said. “And the elevated depression risk among siblings of IBD patients may reflect caregiver fatigue if the siblings have a role in caring for the patient.”

What surprised researchers was that patients with depression were prone to IBD. Zhang speculates that this discovery may have to do with what is known as the gut-brain axis, a scientifically established connection between the gastrointestinal system and the central nervous system, which consists of the spinal cord and the brain.

For example, he said, inflammation of the brain, which plays a role in depression, may be linked to the inflammation of the gastrointestinal tract, a hallmark of IBD.

The researchers are not sure why siblings of patients with depression are more likely to be diagnosed with IBD. Zhang surmises that there may be a shared genetic susceptibility for either disease that presents differently in family members.

Zhang hopes that the study findings will encourage health care professionals to take both family history and the relationship between gastrointestinal and mood disorders into consideration when evaluating or treating patients with either IBD or depression.

Through more research and better understanding of the gut-brain axis, he envisions leveraging the newfound connection between the conditions to improve the prevention, diagnosis and treatment of IBD and mental disorders.

Source: University of Southern California – Health Sciences