Microbiota mitochondria disorders as hubs for early age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota—mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch’s membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch’s membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)—now called postbiotics—in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

Dietary Marine Hydrolysate Improves Memory Performance and Social Behavior through Gut Microbiota Remodeling during Aging

“…In addition, previous studies have highlighted the essential role of mitochondria in the communication between the gut and brain [77,78]. The modulation of mitochondria, and especially a decrease in the activity of mitochondrial electron transfer complexes, is also associated with behavioral dysfunctions during aging [79,80].…”

The influence of microbiota on ferroptosis in intestinal diseases

“… 95 Recent research has shown that probiotics have a protective effect on mitochondria. 54 , 96 For instance, butyrate in cell lines derived from patients with autism has been found to regulate mitochondrial functions, including enhancing oxidative phosphorylation and β-oxidation under physiological stress or mitochondrial dysfunction 54 and activating the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) signaling axis in NSC34-G93A cells to regulate mitochondrial biogenesis. 55 However, another study suggested that mitochondrial function and glutathione peroxidase 4 (GPX4)-dependent ferroptosis were boosted under the condition of supplementing butyrate.…”

Cellular and molecular insights into microbiota-mitochondria interplay, therapeutic biomarkers and interventional approaches in COVID-19: A review

“…The metabolic functions of nutrients are similar in both the microbiome and mitochondria. In addition, they have many structural and functional similarities and several proteins that regulate related or even the same metabolic processes (Fehér et al, 2022). According to recent findings, the microbiota interacts with the host cell, particularly by interacting with the mitochondria and microbial metabolites that also affect mitochondrial function and biogenesis (Zhu et al, 2022).…”