The Aging of the Gut Microbiome in Alzheimer's Disease

The microbes of the human gut change with age, losing beneficial populations that promote tissue function throughout the body via the metabolites they generate, and gaining harmful populations that generate chronic inflammation and tissue dysfunction. The causes of this problem are varied and still under investigation, but it seems very plausible that methods of reversing the age-related alterations in microbial populations can be established. For example, fecal microbiota transplantation has been shown to restore a youthful gut microbiome and extend life in killifish, and is already used in human medicine for conditions in which pathogenic bacteria have overtaken the intestine. Equally, it seems likely that some novel, tailored form of high dose probiotic therapy could achieve similar results.

Generally, the gut microbial communities in human are stable; however, they can be altered in the different conditions by the effects of various factors. Recently, the studies of several groups have been demonstrated that various diseases, including intestinal diseases and more systemic diseases such as diabetes, metabolic syndrome, and neurodegenerative disorders, including Alzheimer's disease (AD) and others, are related to the imbalance of gut microbiota called "dysbiosis". Occurrence and development of AD and other neurodegenerative disorders may be accompanied by the gut microbiome dysbiosis, inflammation, and dysfunction of the gut-brain axis. It has been speculated that AD may appear during the aging of immune system based on the theory of age-related dysbiosis derived from the association between gut microbiota and AD, which has been evidenced by clinical and experimental studies.

Generally, the traditional ecological measures are used to characterize the composition of the gut microbiome, including richness (the number of unique operational taxonomic units, OTUs, present in a participant), alpha diversity (the richness and abundance of OTUs within each participant), and beta diversity (the similarity or difference in composition between participants). Declined microbial richness and diversity as well as a distinct composition of the gut microbiome were found in AD patients. The levels of differentially abundant genera were correlated with cerebrospinal fluid (CSF) biomarkers of AD pathology. In short, definite genera as more abundant in AD were related to greater AD pathology, whereas genera as less abundant in AD were associated with less AD pathology.

There is also a close interaction between gut microbes and the local as well as systemic immune system. In general, the gut dysbiosis could lead to dysfunctions of both innate and adaptive immune through several ways, such as changing antigen presentations, cytokines production, and lymphocyte functions, as well as increasing inflammation, etc., also can cause the gut-brain axis malfunction. In AD patients, the molecular and cellular alterations involving immune cells, such as T cells, B cells, microglia, etc., as well as immune mediators, occur not only in the peripheral blood, but also in the brain and the CSF, which may be associated with triggering immune response by the gut dysbiosis. The gut dysbiosis impacts on innate and adaptive immune response in AD patients obviously via activating immune/inflammatory cells, shifting them into inflammatory type to enhance immune mediated inflammatory response, and promoting neurodegeneration in the brain. The gut dysbiosis in AD was obviously correlated with more T helper 1 (TH1) cell infiltration into the brain, and increased T-cell infiltration in the brain parenchyma and peripheral T-cell responses to amyloid-β have been found in AD patients.

Link: https://doi.org/10.3389/fnagi.2020.544235

Comments

Since fecal transplants are very expensive and our regulatory overlords have made them difficult to obtain, the do it yourself option has become common. google and youtube have no shortage of instructions on this easy but decidedly unglamorous procedure. I assume the younger the donor the better.Grab some of their blood while you're at it....
https://pubmed.ncbi.nlm.nih.gov/31972620/

Posted by: august33 at November 13th, 2020 3:35 AM

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