Towards early detection of neurodegenerative diseases: A gut feeling

Abstract

The gastrointestinal tract communicates with the nervous system through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the enteric nervous system, the vagus nerve, the immune system, endocrine signals, the microbiota, and its metabolites. Alteration of communications in the gut-brain axis is emerging as an overlooked cause of neuroinflammation. Neuroinflammation is a common feature of the pathogenic mechanisms involved in various neurodegenerative diseases (NDs) that are incurable and debilitating conditions resulting in progressive degeneration and death of neurons, such as in Alzheimer and Parkinson diseases. NDs are a leading cause of global death and disability, and the incidences are expected to increase in the following decades if prevention strategies and successful treatment remain elusive. To date, the etiology of NDs is unclear due to the complexity of the mechanisms of diseases involving genetic and environmental factors, including diet and microbiota. Emerging evidence suggests that changes in diet, alteration of the microbiota, and deregulation of metabolism in the intestinal epithelium influence the inflammatory status of the neurons linked to disease insurgence and progression. This review will describe the leading players of the so-called diet-microbiota-gut-brain (DMGB) axis in the context of NDs. We will report recent findings from studies in model organisms such as rodents and fruit flies that support the role of diets, commensals, and intestinal epithelial functions as an overlooked primary regulator of brain health. We will finish discussing the pivotal role of metabolisms of cellular organelles such as mitochondria and peroxisomes in maintaining the DMGB axis and how alteration of the latter can be used as early disease makers and novel therapeutic targets.

Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta‐analysis

“…29,30 The hypothesis about the role of dysbiosis is supported by the connection between the gastrointestinal tract and the nervous system via the gut-brain axis, since alterations in this pathway have been considered major sources of neuroinflammation. 12,35 F I G U R E 4 Funnel plot of the studies included in meta-analysis.…”

“…Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers, even neurodegenerative or psychiatric conditions, such as chronic depression, Parkinson's disease, and ASD 29,30 . The hypothesis about the role of dysbiosis is supported by the connection between the gastrointestinal tract and the nervous system via the gut–brain axis, since alterations in this pathway have been considered major sources of neuroinflammation 12,35 …”

Nonlinear DNA methylation trajectories in aging male mice

“…Interestingly, many neurodegenerative diseases are accompanied by gastrointestinal symptoms, which can even manifest earlier than dysfunctions in the CNS (reviewed in ref. 68 ). Moreover, the human ENS was shown to express risk genes for extraintestinal diseases 15 .…”

Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases

“…Importantly, these highly diverse intestinal microorganisms participated not only in maintenance of a healthy gut, but also in pathogenesis and progression of many diseases where dysbiosis occurs, via various mechanisms ( Mosca et al, 2016 ; Hughes et al, 2018 ; Chen et al, 2019 ; Laniewski et al, 2020 ; Wang et al, 2021 ; Geng et al, 2022 ). Though each disease presents a unique disturbance of gut microbiota, some species appear to be involved across multiple diseases, and therefore have become targets of interest, as they may either provide an insight to a common pathogenic pathway ( Makdissi et al, 2023 ), or hold the potential to be used as a marker or target for diagnosis or treatment of these diseases ( Mamic et al, 2023 ). The Gram-negative anaerobe Akkermansia muciniphila , which belongs to Verrucomicrobia phylum, is one of such species that has been shown to be dysregulated in an increasing number of diseases such as metabolic disorders ( Xu et al, 2020 ) and intestinal diseases ( Liu et al, 2022 ).…”