Microbiota Signaling Pathways that Influence Neurologic Disease

Abstract

Though seemingly distinct and autonomous, emerging evidence suggests there is a bidirectional interaction between the intestinal microbiota and the brain. This crosstalk may play a substantial role in neurologic diseases, including anxiety, depression, autism, multiple sclerosis, Parkinson's disease, and, potentially, Alzheimer's disease. Long hypothesized by Metchnikoff and others well over 100 years ago, investigations into the mind-microbe axis is now seeing a rapid resurgence of research. If specific pathways and mechanisms of interaction are understood, it could have broad therapeutic potential, as the microbiome is environmentally acquired and can be modified to promote health. This review will discuss immune, endocrine, and neural system pathways that interconnect the gut microbiota to central nervous system and discuss how these findings might be applied to neurologic disease.

The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

“…The bidirectional nature of the gut-brain axis is also proposed by Cox and Weiner [21]. We recently proposed that in CNS inflammatory diseases the association with the gut microbiota is bidirectional [24].…”

“…Remarkably, their study also suggests that the treatment with immunomodulatory drugs shape the microbiota strongly, promoting differences that are higher than those found in patients with MS. The adult MS microbiota complexity is covered by the reviews of Freedman et al [19], Pröbstel and Baranzini [20], and Cox and Weiner [21]. These studies highlight the current limitations of microbiota studies in disease populations, owing to interindividual variability, the effects of multiple possible environmental factors that could affect the composition of the microbiota, and also the relevant role of immunomodulatory drugs in shaping the microbiota.…”

“…Mechanistically, dysfunctional IL-10-producing T cells were associated with the role of the MS microbiota regulating disease. The gut-brain axis in MS is evaluated by Cox and Weiner [21] from neuronal, neuroendocrine, and immunological perspectives. The association between the microbiota and other neurological diseases such as Parkinson's disease, mood disorders such as anxiety, aggressive behavior, and autism are also covered.…”

Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

“…Assessments of the number of bacterial species present in the human gut vary widely among studies, but it is generally accepted that individuals harbor more than 1000 microbial, species-level phylotypes (Lozupone et al, 2012) that can communicate via a QS mechanism (Bivar Xavier, 2018). The role of the human gut microbiome in health and disease has been the topic of broad research, and a role for the bacterial commensals in various neurological conditions is well accepted (Byrd et al, 2018;Caballero-Villarraso et al, 2017;Cox and Weiner, 2018;Friedland and Chapman, 2017;Ho et al, 2018;Kitai and Tang, 2018;Marietta et al, 2018;Perez-Pardo et al, 2017;Roszyk and Puszczewicz, 2017;Sherwin et al, 2018;Thion et al, 2018;Yang and Duan, 2018). Indeed, the gastrointestinal tract is deeply connected with the central nervous system through the gut-brain axis, an interconnected and bidirectional network of neuroendocrine signals and immunological factors.…”

The intestinal microbiome and Alzheimer's disease: A review

“…During maturation, microglia remain in an immature status in the absence of microbiota and can be rescued by the administration of short‐chain fatty acids (SCFAs) . Lactobacillus reuteri can suppress neuroinflammation in astrocytes in the brain by promoting the production of indole‐3‐aldehyde and indole‐3‐propionic acid, which are then transported across the BBB …”