However, there exists another tool involving the gut microbiome (GM) which plays a significant role in supporting all RM tools both directly and indirectly (http://dx.doi.org/10.3233/JAD-220313). In Neurological diseases, one of the major causes is the aggregation of abnormal proteins causing inflammation and neurological dysfunction. A standard RM approach may have limited success unless the aggregations are scavenged. Enhancing the Microglia through GM scavenges and resumes homeostasis in the brain. The findings are based on clinical research that established the influence of biological response modifier glucans (BRMG) to control GM, preventing aggregation and therefore propagation of abnormal proteins to the brain.
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Extensive research by the European Metagenomics of the Human Intestinal Tract (MetaHIT) and the NIH-funded Human Microbiome Project (HMP), which studied the gut metagenomes of 1,070 individuals, revealed the human gut to have 30 times more genes than the human genome. Thus, GM is viewed as the second genome of the body because of the extent of its functionality.
Investigative procedures such as the 16S rRNA-encoding gene sequencing along with metagenomic and microbial transcriptome, proteome, and metabolome analyses have increased the knowledge of the human microbiome, including the gut. Healthy adults have more than 1,000 species of bacteria, with Bacteroidetes and Firmicutes being the dominant phyla. However, the health of GM differs in patients. Gut microbes release short-chain fatty acids (SCFAs) from indigestible dietary fibers. The SCFAs are the energy source for intestinal mucosa, and they are vital for regulating both the immunity and tumorigenesis in the gut. Other than the SCFAs, the GM produces many other microbial products such as uremic toxins, bile acids, trimethylamine-N-oxide (TMAO), SCFAs, lipopolysaccharides (LPSs), nitric oxide, vitamin K, vitamin B complex, gut hormones, and neurotransmitters which modulate metabolism and body function.
Studies have found a synergy between the gut microbiome and MSC-based regeneration, especially in the case of inflammatory bowel disease (IBD). Gut bacterial secretions control the cytokine gene transcription and surface protein expressions in MSCs. They also change the differentiation potentials and improve the immunomodulation ability of bone marrow MSCs. Nagashima and colleagues reported on the symbiotic relationship between a sub-epithelial population of MSCs and the gut microbiome wherein the former facilitates microbiome diversity and regulates IgA production. Other means to restore the Bacteroidetes/Firmicutes ratio, hepatocyte repair, and gut epithelial cell regeneration include MSC infusion and NOD2 sensors. Conditioning treatments such as hematopoietic stem cell transplantation (HSCT), chemotherapy, radiotherapy, and immunosuppressive therapy disrupt the gut microbiome. Valid strategies that work to counter the side effects include lactobacillus administration, probiotics, prebiotics, and fecal microbiota transplantation (FMT).
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