NeuroConX 2018 blog |

anatomy-160524_640

Gut microbiota play a significant role in regulating the bidirectional communication within what has come to be known as the gut-brain axis. Communication between the gut and the brain can occur via direct neuronal communication, endocrine signaling mediators or through the immune system. Changes in microbial compositions can influence behaviour and cognition, while changes in the nervous system can indirectly influence the gut microbiome, forming the bi-directional communication that defines the gut-brain axis. Such shifts in gut microbiome composition have been associated with various neuropsychiatric and neurodegenerative conditions and can precede or occur during, the course of their development.

These recent findings suggest that manipulating the MBT-Candara gut microbiota may offer a novel approach to altering brain function and treating neurological disease. Microbiome Therapeutics, founded in 2009 as NuMe Health by John Elstrott, Dale Pfrost, and Mark Heiman, is developing and marketing novel therapeutics to promote a healthy microbiome. These microbiome modulators deliver specific nutrients to the gastrointestinal microbiome to support a healthy diversity of microbiota. Their blend of prebiotics is comprised of natural products derived from food and is designed to increase the production of short-chain fatty acids (SCFAs), prime the gastrointestinal immune system, and reduce intestinal permeability. BiomeBliss^TM will be sold as a dietary supplement and is expected to come out later this year.

While BiomeBliss was originally formulated to target blood sugar, satiety and regularity, the potential application to brain health is all too obvious. These SCFAs are microbial metabolites that modulate microglia activation, stimulating immune responses and controlling inflammation. Changes in microbiome composition, such as those identified in neurodegenerative diseases result in a reduction in health promoting neuroactive SCFAs. This decrease in SCFA concentration can contribute to gut leakiness and inflammatory responses, characteristic of these diseases. This, in turn, may drive neuroinflammation, increase oxidative stress, and promote protein aggregation. In a recent paper, Dr. Giulio Maria Pasinetti, a previous NeuroConX speaker, reported that the generation of select SCFAs can interfere with the aggregation of abnormal misfolded proteins in the brain in neurodegenerative diseases. For an overview of the microbiome in neurological disease, you can check out a recent review by Dr. Silke Appel-Cresswell, who will be speaking at NeuroConX 2018.

Dr. Mark Heiman, of Microbiome Therapeutics will be just one of the microbiome companies presenting at our upcoming NeuroConX meeting, this July. Join Dr. Heiman and many others to discuss more about how the gut microbiome influences brain health, at NeuroConX 2018.

The Genetic Link Between Parkinson’s Disease and the Gut

January 16, 2018 by PEIBioAlliance Leave a comment

There is growing evidence that the status of the intestinal environment heavily influences CNS function. This gut-brain axis may play an important role in the development of neurological diseases, with Parkinson’s disease (PD) being no exception. One of the most recent pieces of evidence is the finding that several variants in the leucine-rich repeat kinase 2 ( LRRK2 ) gene raise or lower risk, not only for PD, but also for Crohn’s disease, an inflammatory bowel disorder. This work, published this month in the journal, Science Translational Medicine, was led by researchers Inga Peter and Judy Cho at the Icahn School of Medicine at Mount Sinai, New York.

These findings further highlight what an important player the gut is in PD pathogenesis. Gastrointestinal dysfunction is prevalent amoung PD patients and occurs early, well before the onset of motor symptoms. A chronic low-grade intestinal inflammation can ultimately lead to neuroinflammation, and neurodegeneration in PD may arise from a cascade of events starting in the gut, according to Malu Tansey, a speaker at NeuroConX 2015. This gut inflammation can also influence synuclein pathology, which appears in both the enteric and central nervous system. Heiko Braak has proposed that synuclein pathology, a key pathological hallmark of PD, actually begins in the gut of PD patients and travels to the brain via the vagus nerve.

Lrrk2

The immune status of the gut is strongly influenced by the gut microbiome, which constitutes 100 trillion microorganisms, the vast majority of which are living in the gut microbiota. In PD patients, the intestinal microbiome is altered and associated in a functional way to clinical phenotype, according to Filip Scheperjans, who is scheduled to present his work at the upcoming NeuroConX 2018 microbiome meeting in July. In a mouse model of PD, PD-derived microbiota enhanced alpha-synuclein-mediated motor dysfunction. These changes in microbiota are believed to be an early event in the development of PD and, with further investigation, may serve as an early biomarker and possibly even a therapeutic target.

The Peter and Cho study identified two variants of the Lrrk2 gene associated with Crohn’s disease. One, ND2081D, was associated with an increased risk for Crohn’s, while N551K appeared to be protective, associating with a lower risk. The Lrrk2 mutation, G2019S, is the major genetic cause of familial and sporadic PD and has been shown to have deleterious effects through increased kinase activity. Similar elevations in kinase activity have been associated with ND2081D and both variants are able to bump up phosphorylation by about 30 percent in cell-free experiments, suggesting a similar mechanism of action. Association studies show the Lrrk2 variant, ND2081D, increases the risk of both Crohn’s disease and PD, suggesting these two diseases may share risk factors. This is consistent with the increased risk of PD amoung those patients suffering with inflammatory bowel disease.

While the mechansim underlying this co-morbidity requires further exploration, it offers yet another link in the connection between the gut and brain. For more information and cutting edge research on the role of the gut microbiome in brain health and disease, please join us at NeuroConX 2018.