Butyrate Made by Gut Bacteria Linked to Depression
Among people with Parkinson’s disease, lower levels of a bacterial compound called butyrate in the gut are associated with more severe depression, a new study indicates.
Results also revealed that altered butyrate levels in Parkinson’s patients are associated with epigenetic changes in these individuals’ cells.
The study, “Bacterial Butyrate in Parkinson’s Disease Is Linked to Epigenetic Changes and Depressive Symptoms,” was published in Movement Disorders.
The human digestive system is home to billions of bacteria and other microorganisms, collectively known as the gut microbiome. An emerging body of research has suggested that the gut microbiome is altered in people with Parkinson’s. One of the alterations that has been noted is low levels of a bacterial metabolite called butyrate. However, the effects of these changes remain poorly understood.
Here, an international team of scientists conducted analyses of data collected from 55 Parkinson’s patients and 55 people without the disease (controls). The collected data included evaluations of stool and blood samples, as well as clinical data.
In line with prior findings, this analysis found that Parkinson’s patients had reduced levels of fecal butyrate, and lower abundances of butyrate-producing bacteria (Roseburia, Romboutsia, and Prevotella) in their guts.
Statistical analyses also showed that, among those with Parkinson’s, lower levels of butyrate were associated significantly with more severe depression, as measured by the Geriatric Depression Scale (GDS-15).
The scientists then conducted a series of analyses to look for epigenetic changes associated with altered butyrate levels. Epigenetics refers to chemical alterations made to DNA molecules that do not alter the genetic sequence, but can change how the DNA is “read” — for instance, increasing or decreasing the activity of individual genes.
“This study is the first to examine the possible role of epigenetic changes as a link between gut microbiota, its metabolites, and the pathophysiology [disease-related biology] of neural and immune cells in” Parkinson’s, the researchers wrote.
The researchers identified a number of butyrate-associated epigenetic changes in Parkinson’s patients’ neurons and immune cells. Specific changes varied among different types of cells, with the strongest changes seen in innate immune cells like neutrophils and monocytes. The scientists noted that prior research also has indicated butyrate can modulate immune activity.
“Our results suggest that butyrate may impact [Parkinson’s] through epigenetic effects on innate immune cells,” the researchers wrote.
The team then compared the genes that are affected by butyrate-associated epigenetic changes, with genes that are known to be associated with various diseases. This revealed significant overlap between the butyrate-affected genes and genes that are known to affect the risk of Parkinson’s disease or inflammatory bowel disease (IBD). However, there was little overlap with genes associated with other neurological disorders, such as Alzheimer’s disease.
“Our results suggest that patterns of butyrate-related epigenetic changes in [Parkinson’s] are most similar to those found in inflammatory bowel disease and clearly less similar to those found in Alzheimer’s disease,” the researchers wrote, adding that these data “suggest that microbiome-related epigenetic modulation could be a mechanism relating GI [gastrointestinal] disorders and” Parkinson’s.
“Combining metabolite, microbiome, clinical data, and DNA methylation profiling, our study is the first to reveal a possible relation between gut microbiome metabolite production and epigenetic changes, implicating immune and neural pathways in [Parkinson’s] patients with potential impact on depressive symptoms,” the scientists concluded.