The organization of behavior: A neuropsychological theory

I. the origin of species by means of natural selection

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health. In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.

The gut microbiota-brain axis in behaviour and brain disorders.

Research into the role of the gut microbiome in modulating brain function has rapidly increased over the past 10 years, albeit chiefly in animal models. Increasing clinical and preclinical evidence implicates the microbiome as a possible key susceptibility factor for neurological disorders, including Alzheimer's disease, autism spectrum disorder, multiple sclerosis, Parkinson's disease, and stroke. Cross-sectional clinical studies are bolstering the concept of altered microbial composition contributing to the pathophysiology of such diseases. However, the field is nascent, and interpretation of such data is often difficult given that the composition of the microbiome is influenced by various factors such as diet and exercise. Longitudinal studies and randomised controlled trials in humans are needed to find out if targeting the microbiome can yield novel therapeutic strategies. Systems biology approaches will also be important in integrating such data with genomic and metabolomic datasets from clinical cohorts with neurological disease to help guide individual treatment selection.

The gut microbiome in neurological disorders.

Sociability can facilitate mutually beneficial outcomes such as division of labor, cooperative care, and increased immunity, but sociability can also promote negative outcomes, including aggression and coercion. Accumulating evidence suggests that symbiotic microorganisms, specifically the microbiota that reside within the gastrointestinal system, may influence neurodevelopment and programming of social behaviors across diverse animal species. This relationship between host and microbes hints that host-microbiota interactions may have influenced the evolution of social behaviors. Indeed, the gastrointestinal microbiota is used by certain species as a means to facilitate communication among conspecifics. Further understanding of how microbiota influence the brain in nature may be helpful for elucidating the causal mechanisms underlying sociability and for generating new therapeutic strategies for social disorders in humans, such as autism spectrum disorders (ASDs).

Microbiota and the social brain

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

Recent times have seen an increasing move towards harnessing the health-promoting benefits of food and dietary constituents while providing scientific evidence to substantiate their claims. In particular, the potential for bioactive protein hydrolysates and peptides to enhance health in conjunction with conventional pharmaceutical therapy is being investigated. Dairy-derived proteins have been shown to contain bioactive peptide sequences with various purported health benefits, with effects ranging from the digestive system to cardiovascular circulation, the immune system and the central nervous system. Interestingly, the ability of dairy proteins to modulate metabolism and appetite has recently been reported. The ghrelin receptor (GHSR-1a) is a G-protein coupled receptor which plays a key role in the regulation of food intake. Pharmacological manipulation of the growth hormone secretagogue receptor-type 1a (GHSR-1a) receptor has therefore received a lot of attention as a strategy to combat disorders of appetite and body weight, including age-related malnutrition and the progressive muscle wasting syndrome known as cachexia. In this study, a milk protein-derivative is shown to increase GHSR-1a-mediated intracellular calcium signalling in a concentration-dependent manner in vitro. Significant increases in calcium mobilisation were also observed in a cultured neuronal cell line heterologously expressing the GHS-R1a. In addition, both additive and synergistic effects were observed following co-exposure of GHSR-1a to both the hydrolysate and ghrelin. Subsequent in vivo studies monitored standard chow intake in healthy male and female Sprague-Dawley rats after dosing with the casein hydrolysate (CasHyd). Furthermore, the provision of gastro-protected oral delivery to the bioactive in vivo may aid in the progression of in vitro efficacy to in vivo functionality. In summary, this study reports a ghrelin-stimulating bioactive peptide mixture (CasHyd) with potent effects in vitro. It also provides novel and valuable translational data supporting the potential role of CasHyd as an appetite-enhancing bioactive. Further mechanistic studies are required in order to confirm efficacy as a ghrelinergic bioactive in susceptible population groups.

https://www.mdpi.com/1422-0067/19/9/2780/pdf

Shauna E. Wallace-Fitzsimons

Papers

The Microbiota-Gut-Brain Axis

A Dairy-Derived Ghrelinergic Hydrolysate Modulates Food Intake In Vivo