Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions

Abstract

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut–brain axis.

Marine Natural Products: Promising Candidates in the Modulation of Gut-Brain Axis towards Neuroprotection

“…In addition to the above-mentioned methods of communication, the microbiota can directly synthesis the neuroactive mediators like GABA [ 42 ], 5-HT, norepinephrine, and dopamine [ 43 ]. Considering the gut-brain axis, the migration of toxic agents from gut to brain could trigger cell migration in astrocytes via the activation of the PI3K/Akt/mTOR pathway [ 11 ]. Consequently, the aforementioned mediators have critical roles in several body procedures, including apoptosis, inflammation, oxidative stress, as well as cell migration and proliferation towards homeostasis and even pathological situations of different organs.…”

“…Accordingly, gamma-aminobutyric acid (GABA), glutamine, 5-hydroxytryptamine (5-HT), histamine, glial cell function, synaptic pruning, blood-brain barrier function (BBB), and myelination are important players [ 6 , 10 ]. Considering the gut-brain axis, migration of toxic agents from gut to brain trigger astrocyte activation via the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway [ 11 ]. Instead, during pathological conditions, the aforementioned pathways/mediators tend to be involved in many devastating neurological situations.…”

“…Marine natural products such as carotenoids, polysaccharides, phytosterols, terpenoids, macrolactins, and alkaloids apply potential antioxidant and scavenging characteristics in modulating the properties of the gut-brain axis. Recent reports have shown the association of GM and neurodegenerative diseases [ 2 , 11 , 16 ] through those inflammatory/apoptotic/oxidative stress pathways. To the best of our knowledge, this is the first review highlighting the potential of marine-derived natural products in modulating the gut-brain axis towards neuroprotection.…”

Effect of Yuzu (Citrus junos) Seed Limonoids and Spermine on Intestinal Microbiota and Hypothalamic Tissue in the Sandhoff Disease Mouse Model

“…Several studies have shown that bilateral signals between the brain and intestine help to maintain homeostasis within the body and contribute to longevity [ 12 , 13 , 14 , 15 ]. Approximately 1000 species and 100 trillion bacteria are present in the human gastrointestinal tract [ 16 ], and it is clear that these bacteria play important roles in energy uptake from ingested food [ 17 , 18 ].…”

“…SCFAs also have been seen to specifically alter hematopoiesis, promote immunoglobulin A(IgA) responses [ 37 ], alter T cell homeostasis [ 38 , 39 ], and promote neurogenesis [ 40 ]. The potential therapeutic role of SCFAs is also being examined with respect to the gut-brain axis, such as Parkinson’s, autism, and schizophrenia [ 12 , 13 , 14 , 15 ]. It is plausible that this gut-brain axis in SD may function by strengthening the production of intestinal microbiota metabolites in SD mice by treating with limonoids and Spm.…”