Gut Inflammation Helps Drive Disease, Mouse Study Indicates

Another study explores changes in the gut-brain axis

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A group of mice in a huddle, eating pellets.

In a mouse model of Parkinson’s disease animals show signs of inflammation in the gut, and treatment with cell therapies that reduce this inflammation help to ease symptoms of Parkinson’s, according to a new study.

These results suggest that inflammatory conditions in the gut may contribute to the development and progression of the disease, the researchers said. They noted that this study adds to a growing field of research on how changes in gut health are involved in Parkinson’s, commonly referred to as the gut-brain axis (GBA).

“These promising data … support the active participation of the GBA in the early and late stages of neurodegeneration and also advance the potential of cell-based regenerative medicine for” Parkinson’s, the researchers wrote.

The study, “Inflammatory gut as a pathologic and therapeutic target in Parkinson’s disease,” was published in Cell Death Discovery.

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Parkinson’s disease is caused by the death and dysfunction of cells in the brain that make a chemical messenger called dopamine. The disease usually is characterized by toxic clumps of the alpha-synuclein protein in the brain, which are thought to drive disease progression.

Scientists in the U.S. and Mexico conducted a series of experiments using a mouse model of Parkinson’s in which the mice were engineered genetically to produce excessive amounts of alpha-synuclein protein. Compared to wild-type (non-Parkinson’s) mice, the Parkinson’s mice showed marked deficits on measures of coordination and had fewer dopamine-producing cells in their brains.

The Parkinson’s mice also showed pronounced reduction in gut motility and gastric emptying — the ability to move food through and out of the intestines during the process of digestion. Analyses of bacteria in the mice’s feces suggested pronounced changes in their gut microbiome (the community of bacteria that live in the digestive tract).

“Both gut and brain from [Parkinson’s] mice exhibited upregulation of inflammation-associated microbiota and cytokines [signaling molecules],” the researchers wrote.

hUCB stem cell treatment

Some of the Parkinson’s mice were treated with plasma (the non-cell part of blood) derived from human umbilical cord blood (hUCB), which was administered via injection into the mice’s bloodstream. Other mice were treated with hUCB plasma and also stem cells isolated from hUCB.

Stem cells are able to grow into other cell types, and can modulate the activity of nearby cells by secreting various signaling molecules. In particular, these cells have notable anti-inflammatory properties. Prior research done in other Parkinson’s models has suggested that hUCB stem cell treatment can help to normalize gut health.

In the present study, treatment with hUCB plasma and stem cells led to significant improvements in motor function for Parkinson’s mice, though the treated mice still showed deficits compared to wild-type animals. Treated mice also had less loss of dopamine-producing neurons and less alpha-synuclein accumulation compared to untreated Parkinson’s mice.

Similarly, the stem cell treatment improved gut motility and had normalizing effects on the gut microbiome, though treated mice still showed differences compared to wild-type mice.

The treatment “significantly reduced inflammation-linked gut microbiota, decreased pro-inflammatory cytokine concentrations, and reduced gut and brain [alpha]-synuclein,” the researchers concluded.

In a final set of experiments, the researchers took homogenates (homogenized tissue) from the mice’s digestive tracts, and used them to treat dopamine-producing nerve cells in dishes.

Results showed that these cells could grow well in gut homogenate from wild-type mice, but showed a marked reduction in cell viability and an increase in inflammatory markers when treated with homogenate from Parkinson’s mice. When homogenate from Parkinson’s mice treated with hUCB plasma and stem cells was used, these detrimental effects were blunted.

Collectively, these findings support the idea that “[a]berrant perturbations in inflammatory microbiomes in the GBA may predispose” toward  Parkinson’s, the researchers wrote.