Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis

Abstract

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut-brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis-all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson's and Alzheimer's diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

“…Gut microbiota can influence the physiopathology of AD also through the synthesis of metabolites that, once absorbed in the systemic circulation, can modulate neural function 103. These metabolites, extensively reviewed by Alkasir et al, may have either neuroprotective or neurotoxic effects 104.…”

“…These metabolites, extensively reviewed by Alkasir et al, may have either neuroprotective or neurotoxic effects 104. For example, Lactobacillus, Lactococcus, Streptococcus and Enterococcus may produce histamine, which acts as a neurotransmitter and an important modulator of neuroinflammation through reduction of tumor necrosis factor-alpha expression in the brain 103,104. Similarly, other bacterial taxa, including Bacillus, Lactobacillus and Bifidobacterium , are able to synthesize neurotransmitters involved in memory and learning function regulation, such as gamma-aminobutyric acid, serotonin, norepinephrine and acetylcholine 103,104…”

Does Akkermansia muciniphila play a role in type 1 diabetes?

“…Whatever the case, it is noteworthy that a specific bacterium, Akkermansia muciniphila , an abundant constituent of the gut microbiota in healthy humans, has been demonstrated to correct host metabolic disorders when given by gavage as a probiotic in obese insulin-resistant mice 2. Nowadays, interest in the role of intestinal microbiota in diseases has widened to cover various types of disease like mental disorders,5 neurodegenerative disorders6 and immune system disorders,7 including autoimmune disorders such as type 1 diabetes 8…”

Gut Microbiota and Host Metabolism: What Relationship

“…Among them, short-chain fatty acids produced from the fermentation of dietary fibers initiate beneficial effects on the host metabolism via the activation of intestinal gluconeogenesis (a mucosal function exerting antidiabetic and antiobesity effects through the activation of gut-brain neural cir-as obesity or type 2 diabetes, either in rodents [1][2][3] or in humans [4][5][6][7]. The growing interest in the influence of intestinal microbiota on diseases has now expanded to "non-metabolic" illnesses such as intestinal or mental disorders [8], disorders of the immune system [9], or neurodegenerative disorders, such as Alzheimer disease or multiple sclerosis [10].…”