Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.

Bridging the Gap: Harnessing Plant Bioactive Molecules to Target Gut Microbiome Dysfunctions in Amyotrophic Lateral Sclerosis

“…Initial studies of the microbiome in ALS consistently found dysbiosis to be present, both through potentially harmful bacterial overgrowth and through the reduced biodiversity of potentially beneficial bacterial strains. These studies proposed that pro-inflammatory dysbiosis might stem from microbial imbalance, compromising the intestinal epithelial barrier and triggering immune/inflammatory responses, thus playing a role in ALS pathogenesis [46]. Patients with ALS who exhibit heightened richness and diversity in their microbiome, along with a higher Firmicutes to Bacteroidetes ratio, are noted to face a heightened risk of premature mortality [47], this association being observed at a later stage in disease progression.…”

Current landscape of fecal microbiota transplantation in treating depression

“…The MGB axis includes neural signal networks, immune signal networks, and chemical signal networks ( 60 , 61 ). First, through the regulation of intestinal peristalsis by the autonomic nervous system, the brain’s exogenous parasympathetic and sympathetic nerves influence the activity of the internal intestinal neuron network, thereby regulating intestinal peristalsis and the rate of content transport ( 62 ). Secondly, the central efferent nerve of the brain, directly or through the enteric nervous system, is in contact with the intestinal secretory cells, regulating the secretory substances of the luminal cells, directly acting on the microbiome, and regulating microbial host signaling.…”