Therapeutic potential of Short Chain Fatty acid production by gut microbiota in Neurodegenerative disorders

Dietary fibers are a major source of short-chain fatty acids (SCFAs) in the body, and the fermentation products of SCFAs induced by intestinal microbiota affect energy metabolism. Apart from serving as energy source in the intestines, SCFAs also inhibit autophagy, Nucleotide-binding oligomerization domain-containing protein (NOD), LRR and Pyrin domain-containing protein 3 (NLRP3) inflammasome. SCFAs provide numerous therapeutic benefits through their influence on cognitive functioning and Neuro-Degenerative Diseases (NDD) pathophysiology. Additionally, NDDs are associated with abnormalities in the gut microbiota, including an increased load of pathogens and opportunistic microbes. SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of NDD and cognitive decline by regulating inflammation and oxidative stress. Basically, SCFAs functions as a cofactor for the host's mitochondrial enzymes and are being studied for its ability to reverse the alteration in the gut microbiota seen in many NDDs and cardiac diseases. In the present review, the focus is on the detrimental and beneficial roles of SCFA in NDD emphasizing the effects of SCFA on following phenomenon; (i) alteration in gut microbiota profile associated with NDD, (ii) the molecular mechanism of metabolic regulation by SCFA's, and itsco-relation with NDD (iii) Use of mitochondrial antioxidants as a strategy for maintaining microbiota diversity in the gut (iv) the future direction of metabolism and neurodegeneration in the gut-brain axis. In addition, the interplay between gut microbiota, SCFAs, epithelial barrier and neuro-immune signaling in neurodegeneration has also been reviewed.