It is thought that an appreciable fraction of the chronic inflammation of aging is caused by changes in the gut microbiome. There is a bidirectional interaction between the immune system and the microbial populations of the intestinal tract. The immune system gardens these populations, destroying problematic microbes. Microbes secrete metabolites and other molecules that can either benefit or harm the function of the immune system, the harms caused particularly by those microbes capable of provoking a sustained inflammatory response. The immune system declines with age for a range of reasons, and reduced efficacy in immune surveillance of gut microbes allows harmful microbial populations to grow in number, in turn further degrading immune function by inducing a state of chronic inflammation.
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Many of the common, ultimately fatal age-related conditions are driven by chronic inflammation and the resulting disruption of normal tissue function. This is very much the case for neurodegenerative conditions. Inflammation in the brain is a prominent feature of tauopathies such as Alzheimer's disease, for example, in which toxic aggregates of altered tau protein form and spread in parallel with the inflammation of brain tissue. Researchers have shown that removing pro-inflammatory senescent cells from the brain, using senolytic drugs, reverses pathology in animal models of tauopathy. How much of inflammation in the brain is the result of senescent cells versus the gut microbiome versus other causes? The only way to find out is to remove each potential cause individually and observe the outcome.
In the case of the gut microbiome, strategies exist to reverse age-related changes. Fecal microbiota transplantation from young individuals to old individuals is the most studied of these approaches, well proven in animal models to reset the balance of microbial populations, reduce inflammation, and improve health. It is already used in humans to tackle cases in which pathological bacteria take over the intestines, and thus, given the will and the funding, it would be a comparatively short path to deploy fecal microbiota transplantation in clinical trials involving patients with inflammatory neurodegenerative conditions.
Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease
The gut microbiota plays a key role in modulating the gut-brain axis, which is a bidirectional communication network that involves the central nervous system, the autonomic nervous system (sympathetic and parasympathetic branches), the enteric nervous system, and the hypothalamic-pituitary-adrenal axis. Recent advances have revealed that the microbiota of the human gut has numerous beneficial functions, such as immune system development, resistance to pathogens, vitamin synthesis, production of metabolites such as short-chain fatty acids (SCFAs), nutrient and drug metabolism, and maintenance of the structural integrity of the intestinal mucosal barrier.
In humans, dysbiosis and changes in gut microbiome composition have been found to contribute to inflammatory bowel disease, type 2 diabetes, metabolic syndrome, obesity, colorectal cancer, Alzheimer's disease (AD), and numerous other diseases. AD is a disastrous neurological disorder affecting 5.8 million Americans (aged 65 years or older) in 2020. AD was the sixth most common cause of death in 2017, accounting for 121,404 deaths in the United States, and the fifth most common cause of death among elderly Americans (65+ years). The sizeable economic burden of AD, as well as its growing prevalence, are leading researchers to look for preventive or disease-modifying treatments.
There are various gut microbiota modulation interventions such as diet modification, prebiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). FMT includes the transplantation of the gut microbiota from a donor to a recipient to refurbish the intestinal microflora of the recipient. It has been proven to be a successful treatment for recurrent Clostridium difficile infections. In this review, we summarize the procedure of FMT and its application in the treatment of various neurological disorders with a special emphasis on AD.
Source: Fight Aging!