Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

Abstract

Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). Methods A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79–0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83–0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02–1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. Conclusions These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

Gut Microbiota Interaction with the Central Nervous System throughout Life

“…A recent study using mendelian randomization has shown a potential protective association between increased abundance of Blautia and the risk of developing AD. Specifically, the authors suggested that gut metabolite GABA was associated with a lower risk of AD [ 241 ].…”

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

“…On the other hand, growing evidence has shown that alterations in the gut microbiota composition can alter normal brain function through the so-called gut–brain axis. Following this idea, the bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract plays a key role in the pathogenesis of a variety of neuropsychiatric disorders and AD [ 17 ]. Moreover, regulation of gut microbiota has been implicated in the control of neuroinflammation and AD progression [ 18 ].…”

“…Moreover, regulation of gut microbiota has been implicated in the control of neuroinflammation and AD progression [ 18 ]. Additionally, in opposite direction, AD pathology could affect gut microbiota composition [ 17 , 19 ].…”

Curcumin and Its Derivatives as Theranostic Agents in Alzheimer’s Disease: The Implication of Nanotechnology

“…Although AD is a neurodegenerative disease, however, scientists are considering a new hypothesis that despite the limited bioavailability of curcumin in gut, it has an indirect influence on the CNS that is due to microbiota-gut-brain axis [ 74 ]. It has been stated that gut bacterial metabolites employ their neuroprotective effects in several neurodegenerative disorders like AD [ 74 , 75 , 76 ]. Microbiota–gut-brain axis is a complex but bidirectional system in which gut microbiota (GM) and its composition represent a factor that preserves and determines the brain health [ 77 , 78 ].…”