Sunday, September 24, 2023

Gut-brain axis and its relationship with Parkinson’s disease (Transcript)

Hello, I am Dr. Zaira Medina, recording for Medscape in Spanish; Now let’s talk about the gut-brain axis and its relationship with Parkinson’s disease.

In the last 15 years, the emergence of the microbiota (the trillions of microorganisms inside the body) as a key regulator of gut-brain function has raised the importance of a different axis: microbiota-gut-brain. There are many factors that influence the composition of the microbiota in early life, including infections, mode of birth, antibiotic use, nutritional status, environmental stresses and personal genetics. On the other hand, the microbiota decreases with aging.

At first we can consider that we have more microbes than human cells in a ratio of 1.3:1; The main sites of microbial colonization are the skin, respiratory tract, urogenital tract, eye and gastrointestinal tract. The complexity of the microbial community in the gastrointestinal tract is the most recently studied and the following enterotypes have been proposed: Bacteroides, Prevotella y Ruminococcus as the most dominant. Bacteroides is associated with diets rich in protein or fat and diets rich in carbohydrates are more associated with Prevotella.(1)

We know that the gastrointestinal tract influences brain function and vice versa; There are many potential channels of communication between the intestinal microbiota and the brain, from highly innervated, highly modifiable to subtle molecular systems that are difficult to measure in the gut and near the brain. At the interface between the microbiota and the host lies a network of neurons known as the enteric nervous system, ready to respond directly or indirectly to the microbiota and its metabolites. The enteric nervous system is organized into two ganglion plexuses: submucosal and myenteric.

Parkinson’s disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Motor symptoms include tremors at rest, bradykinesia, stiffness, and altered postural reflexes due to the loss of dopaminergic neurons in the substance. nigra pars compact. Neuron loss is secondary to the accumulation of intraneuronal proteinaceous cytoplasmic inclusions called Lewy bodies, of which the presynaptic protein alpha-synuclein is the main component. Recent evidence suggests that motor symptoms are preceded by dysregulation of gastrointestinal function manifested as bloating, nausea, constipation, gastroparesis, or weight loss and may appear years before motor symptoms. .(2)

Alpha-synuclein accumulates in neurons of the brain and the enteric nervous system; Likewise, it has been suggested that the gastrointestinal tract is responsible for the dissemination of this protein in Parkinson’s disease. There is evidence that alpha-synuclein in the intestine can be transported to the brain through the vagus nerve and exert its effects through the influence of the microbiota or a translation pathway similar to a prion protein and thus increase the risk of developing pathology .

There is also evidence in a group of patients with Parkinson’s disease who Provotella decreases significantly with the increase in species of Enterobacteriaceae, associated with increased levels of postural instability and gait disorder.

Similarly, in a prodromal state in patients with idiopathic REM sleep disorder with a high rate of conversion to Parkinson’s disease, it has been shown that there are important changes in the microbiota and, therefore, we can assume that there is taxonomic units associated with symptoms. motor and non-motor in this situation.

Patients with Parkinson’s disease have significant changes in the intestinal microbiota; In relation to their quality and quantity, many species show the proliferation of bacteria in the small intestine, that is, an increase in the density of bacteria with dysbiosis in the small intestine responsible for poor absorption, bloating o flatulence and worsening of motor symptoms, which may cause a variable response to levodopa treatment. Eliminating bacterial overgrowth can improve gastrointestinal symptoms and motor changes.

A meta-analysis of 223 patients with Parkinson’s disease and 137 healthy controls from different countries revealed that those with the disease often increase gender. Akkermansia which increases intestinal permeability; Another study showed that the most common change reported in Parkinson’s disease is the elevation of Lactobacillus, Akkermansia y Bifidobacterium with the reduction of Lachnospiraceae y Faecalibacterium.(3)

Several lines of research have shown that taking prebiotics can improve non-motor symptoms in patients with Parkinson’s disease. An important observation is that levodopa is metabolized by the human microbiota and may limit its bioavailability and efficacy.

Without a doubt, the microbiota is a focus of research on Parkinson’s disease and other neurological conditions. Thank you very much for your attention, I am Dr. Zaira Medina, because Medscape in Spanish.

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